ArticlePDF Available

Comparative Bioavailability of Synthetic and Natural Vitamin C in Guinea Pigs



This study was undertaken to compare the bioavailabilities of synthetic ascorbic acid and a natural vitamin C which contains bioflavonoids. Adult male guinea pigs were orally dosed with 50 mg of ascorbate and the serum levels measured using a fluorometric method. The two forms of ascorbic acid gave similar peak concentrations of serum ascorbate but the natural vitamin C peaked later and remained in the serum for a longer time period. The bioavailability of the natural vitamin C was significantly greater (148%, p < 0.001) than that of the synthetic ascorbic acid.
Nutrition Reports International, 27, no.4, 1983.
Comparative Bioavailability of Synthetic and Natural Vitamin C in
Guinea Pigs
J.A. Vinson and P. Bose.
Department of Chemistry, University of Scranton, Scranton, PA 18510, USA.
This study was undertaken to compare the bioavailabilities of synthetic ascorbic acid
and a natural vitamin C which contains bioflavonoids. Adult male guinea pigs were
orally dosed with 50 mg of ascorbate and the serum levels measured using a
fluorometric method. The two forms of ascorbic acid gave similar peak
concentrations of serum ascorbate but the natural vitamin C peaked later and
remained in the serum for a longer time period. The bioavailability of the natural
vitamin C was significantly greater (148%, p < 0.001) than that of the synthetic
ascorbic acid.
The requirement of ascorbic acid (vitamin C) is a common property of living
organisms. Practically all animals except the guinea pig, monkey and man can
synthesise this vitamin. Vitamin C plays an important role in many metabolic
reactions including synthesis of collagen [1] and synthesis of proteins of the immune
system [2]. There is now considerable interest in ascorbate supplementation in
amounts that are relatively large when compared to the recommended dietary intake.
This interest is due to recent books by Linus Pauling on the efficacy of ascorbic acid
in the treatment of colds [3] and treatment of cancer [4].
Although natural and synthetic ascorbic acids are chemically identical, citrus fruits
and other natural sources of vitamin C contain other compounds including
bioflavonoids which could affect the bioavailability of ascorbic acid. In fact,
bioflavonoids have been shown to improve the utilisation of ascorbic acid and
increase its storage in guinea pigs [5, 6, 7]. However, human studies have shown
conflicting results. The comparison of serum and urine levels after oral intake of
comparable doses of natural and synthetic vitamin C have led to the conclusion that
natural vitamin C shows greater [8], equal [9], or less [10] availability than synthetic
ascorbic acid. Most recently, Nelson [11] by an intraluminal perfusion technique
found the two forms to be similarly absorbed.
Since the absorption of ascorbate into the plasma determines its metabolic availability
to the tissues [11], the plasma concentrations of the vitamin following an oral dose
may be used to determine the bioavailability of a supplement. Guinea pigs are an
appropriate animal model for vitamin C since the guinea pig, like man, has an active
transport system [12]. Also, the guinea pig minimises the large intersubject variation
in bioavailability which are often seen in human studies. The present study describes
the relative bioavailability of a synthetic and natural vitamin C after a single dosing of
guinea pigs.
Materials and Methods
Subjects: Ten adult male Hartley guinea pigs were assigned to one of two groups on
the basis of weight so that the average weight of the two groups was statistically
identical. They were fed a standard guinea pig chow for several weeks until the time
of the experiment.
Formulations: The two formulations were synthetic L-ascorbic acid (Fisher Scientific
Company, Pittsburgh, PA.) and Renatured vitamin C in Citrus Fruit Media. The
vitamin C in the latter was synthetic ascorbic acid added to natural proteins,
carbohydrates and bioflavonoids 18%, proteins 15% and carbohydrates 30%. The
product was a light brown, water soluble powder.
Dosage Schedule: The guinea pigs were fasted overnight preceding dosing. Each
guinea pig received by means of an analytical pipette 1 ml of a 50 mg/ml ascorbic
acid solution freshly prepared in distilled water. Blood samples (0.2 ml) were taken
from the heart during light ether anaesthesia before dosing and periodically after
dosing. Blood samples were collected with EDTA as an anticoagulant and
centrifuged at 4000 rpm for 10 minutes. Plasma (0.1 ml) was taken for ascorbic acid
analysis and assayed the same day or alternatively the proteins were precipitated with
metaphosphoric acid and the sample frozen at -20°C until analysis within 2 days.
Measurement of Ascorbate: Ascorbic acid was measured in plasma by fluorescence
[13] following precipitation of proteins with metaphosphoric acid and reaction with
1,2-naphthoquinone-4-sulphonic acid. A standard curve was determined using
freshly prepared aqueous standards. Quercetin, a representative bioflavonoid, gave
zero fluorescence at a concentration of 5 mg/100 ml. Thus, bioflavonoids which are
present in the natural vitamin C are not an interference in the assay procedure.
Concentrations of ascorbate in plasma: The results for the determination of ascorbate
in plasma after an oral dosing of 50 mg of ascorbate in the form of synthetic ascorbate
and natural vitamin C are shown in Table 1. The two groups were statistically
compared by means of a student’s t-test. The pre-dose levels were not significantly
different for the two groups. Also, the maximum concentration of ascorbate were not
significantly different (0.221 mg/dl for the synthetic group and 0.214 mg/dl for the
natural group). The peak concentration was reached sooner for the synthetic group,
approximately 1.5 hours after dosing as compared with 2 hours for the natural vitamin
C. The natural vitamin C stayed in the plasma longer than the synthetic ascorbic acid
as it took more than 4 hours for the natural group to return to pre-dose level and less
than 3 hours for those receiving the synthetic material.
Table 1: Mean Plasma Concentrations of Ascorbate (mg/dl). After Oral Administration of Synthetic
and Natural Vitamin C to guinea pigs.
Time (hours)
Plasma Ascorbate Concentration (± SD)
Synthetic Group (n = 5) Natural Group (n = 5)
0 0.080 + 0.014 0.078 + 0.22
0.5 0.140 + 0.034 0.132 + 0.006
1.0 0.204 + 0.029 0.186 + 0.013*
1.5 0.221 + 0.013 0.199 + 0.047**
2.0 0.123 + 0.011 0.214 + 0.017**
3.0 0.076 + 0.018 0.140 + 0.013**
4.0 ----- 0.092 + 0.016
* p < 0.1, Natural vs. Synthetic
** p < 0.001, Natural vs. Synthetic.
Apparent biological half-lives were calculated by a least squares regression analysis
of the plot of log
vs. time over the last three sampling times where the concentration
of ascorbate was decreasing. The half-life of synthetic vitamin C was 1.0 hours and
of the natural material was 1.6 hours. These half-lives are not elimination half-lives
since they also reflect absorptive and distributive phases in ascorbate
Bioavailability of Ascorbate: The relative bioavailability of the two forms was
calculated by comparison of the area under the plasma concentration-time curve after
administration of each formulation. The areas were determined by means of a
planimeter and the results are shown in Table 2. The bioavailability of the natural
vitamin C was 148% that of the synthetic ascorbic acid and the difference was highly
significant (p < 0.001).
Table 2: Area (Arbitrary units) under the Plasma Ascorbate Concentration-time Curve after oral
administration of Synthetic and Natural Vitamin C to Guinea Pigs.
Synthetic Group Natural Group
Subject Weight (g) Plasma Area Subject Weight (g) Plasma Area
530 426 540 627
552 463 545 541
554 419 550 726
570 449 560 647
570 452 560 729
Mean ± S.D.
555 ± 16 442 ± 18 551 ± 9 654 ±78**
** p < 0.001, Natural vs. Synthetic.
Previous guinea pig studies have been long term feeding experiments which have
compared the effects of synthetic ascorbic acid alone or mixed with bioflavonoids.
Parrot [5] in 1948 found that catechin, a bioflavonoid, when given with ascorbic acid
increased the ascorbate levels in the liver, spleen, kidney and adrenals of guinea pigs
and also prevented scourbutic lesion which were present when ascorbic acid was
given alone at a low dose. Blanc and von der Mühll [7] also found a synergistic
action between ascorbic acid and bioflavonoids with respect to the concentration of
ascorbate in the internal organs.
The best quantitative study was by Crampton and Lloyd [6] in 1950 who fed guinea
pigs daily sub-optimal doses of vitamin C (0.5-2.0 mg) in the form of synthetic
ascorbate or orange-grapefruit juice. This vitamin C was given alone or with 100 mg
of rutin, a bioflavonoid. After 42 days, the biological potencies were determined by
measuring the height of the odontoblast cells of the incisor teeth. There was no
difference between the biopotency of natural or synthetic vitamin C. However, rutin
increased the biopotency by an average of 56% and was most effective at low doses
of Vitamin C. However, the large excess of rutin/ascorbic acid of 200/1 to 50/1 is not
realistic for animal of human supplementation because isolated bioflavonoids are
much more expensive than ascorbic acid.
A biological action of bioflavonoids in animals and man was first suggested in 1936
by Szent-Gyorgi [14] who reported that these compounds prevent capillary fragility
and bleeding in scorbutic animals. A dietary role for bioflavonoids is suggested by
evidence of a widespread low-level blood cell aggregation in apparently healthy
human subjects which is inhibited in vitro by bioflavonoids [15].
Somogyi [16] first presented a mechanism for the effect of bioflavonoids on vitamin
C in physiological fluids. He hypothesised that flavonoids act as sparing factors in
slowing down the oxidation of Vitamin C. This antioxidant effect was shown by in
vitro studies with oxidants such as ascorbic acid oxidase, copper and peroxidase.
In the present study, a natural vitamin C product containing bioflavonoids was found
to be more readily absorbed by Guinea pigs than synthetic ascorbate. These results
indicate that human supplementation with natural vitamin C might prove efficacious.
1. Alfano, M.C., Drummond, J.F. and Muller, S.A. Effect of Ascorbic acid on
the Biosynthesis of Basement Membrane Collagen. J. Dent. Res., 54, L107,
2. Vallance, S. Relationship between Ascorbic Acid and Serum Proteins of the
Immune system. Brit. Med. J., 2, 437, 1977.
3. Pauling, L. Vitamin C and the Common Cold. Freeman Publishing Company,
San Francisco, 1970.
4. Cameron, E. and Pauling, L. Cancer and Vitamin C. Warner Books, Inc., New
York, 1979.
5. Cotereau, E.W., Gabe, M., Gero, E. and Parrot, J-L. Influence of Vitamin C
upon the amount of Ascorbic Acid in the organs of the Guinea Pig. Nature,
161, 557, 1948.
6. Crampton, E.W. and Lloyd, L.E. A Quantitative Estimation of the effect of
rutin on the biological potency of Vitamin. J. Nutr., 41, 487, 1950.
7. Blanc, B. and von der Mühll, M. Interaction of a Flavonoid and Vitamin C:
Its influence on the weight of the guinea pig and the vitamin C content of its
organs. Int. Z. Vitaminforsch, 37, 156, 1967.
8. Elmby, A. and Warburg, E. The inadequacy of synthetic ascorbic acid as an
antiscorbutic agent. Lancet, 11, 1363, 1937.
9. Todhunter, E.N. and Fatzes, A.S. The comparison of the utilisation by
college women of equivalent amounts of ascorbic acid in red raspberries and
in crystalline form. J. Nutr., 19, 113, 1940.
10. Pelletier, O. and Keith, M. Bioavailability of synthetic and natural ascorbic
acid. J. Am. Dietet. Assoc., 64, 271, 1974.
11. Nelson, E.W., Streiff, R.R. and Cerda, J.J. Comparative bioavailability of
Folate and Vitamin C from a Synthetic and a Natural source. Am. J. Clin.
Nutr., 28, 1014, 1975.
12. Stevenson, N. and Brush, M.K. The existence and characterisation of Na
Dependent active transport of Ascorbic Acid in the Guinea pig. Am. J. Clin.
Nutr., 22, 318, 1969.
13. Hubman, B., Monnier, D. and Roth, M. Rapid, accurate determination of
Ascorbic Acid in blood plasma. Clin. Chim. Acta., 25, 161, 1969.
14. Bentsath, A., Rusznyak, I. and Szent-Gyorgi, A. Vitamin P: Flavonoids as
vitamins. Nature, 138, 798, 1936.
15. Robbin, R.C. Effect of methoxylated flavones on Erythrocyte aggregation and
sedimentation in blood of normal subjects: Evidence of a dietary role for
flavonoids. Int. J. Vit. Nutr. Res., 43, 494, 1973.
16. Somogyi, J.C. An investigation of substances which inhibit vitamin C
degradation. Z. Vitaminforsch, 16, 134, 1945.
... Studies carried out in guinea pigs showed enhanced uptake of vitamin C into specific organs (e.g., adrenals and spleen) in the presence of flavonoid-rich juices/extracts or purified plant flavonoids (e.g., hesperidin, rutin, and catechin) [42, [61][62][63][64]. Vinson and Bose [65] carried out a pharmacokinetic study in guinea pigs and found a 148% increase in the area under the plasma ascorbate concentration-time curve when administered as citrus fruit media. They also noted that the citrus fruit group demonstrated delayed plasma vitamin C uptake compared with the synthetic vitamin C group [65]. ...
... Vinson and Bose [65] carried out a pharmacokinetic study in guinea pigs and found a 148% increase in the area under the plasma ascorbate concentration-time curve when administered as citrus fruit media. They also noted that the citrus fruit group demonstrated delayed plasma vitamin C uptake compared with the synthetic vitamin C group [65]. Cotereau et al. [42] reported that animals given both vitmain C and catechin not only had four to eight-fold more vitamin C in the organs measured, but they were also the only group without scorbutic-type lesions. ...
... Supplemental vitamin C typically takes about two hours to reach maximal plasma levels following ingestion. An early animal study found that vitamin C provided in citrus fruit media took longer to reach peak plasma concentrations compared with a synthetic vitamin C solution and also provided a larger area under the plasma vitamin C concentration-time curve [65]. These same investigators observed a comparable trend in human subjects supplemented with 500 mg vitamin C in the presence or absence of a citrus fruit extract [81]. ...
Full-text available
Vitamin C (ascorbate) is an essential water-soluble micronutrient in humans and is obtained through the diet, primarily from fruits and vegetables. In vivo, vitamin C acts as a cofactor for numerous biosynthetic enzymes required for the synthesis of amino acid-derived macromolecules, neurotransmitters, and neuropeptide hormones, and is also a cofactor for various hydroxylases involved in the regulation of gene transcription and epigenetics. Vitamin C was first chemically synthesized in the early 1930s and since then researchers have been investigating the comparative bioavailability of synthetic versus natural, food-derived vitamin C. Although synthetic and food-derived vitamin C is chemically identical, fruit and vegetables are rich in numerous nutrients and phytochemicals which may influence its bioavailability. The physiological interactions of vitamin C with various bioflavonoids have been the most intensively studied to date. Here, we review animal and human studies, comprising both pharmacokinetic and steady-state designs, which have been carried out to investigate the comparative bioavailability of synthetic and food-derived vitamin C, or vitamin C in the presence of isolated bioflavonoids. Overall, a majority of animal studies have shown differences in the comparative bioavailability of synthetic versus natural vitamin C, although the results varied depending on the animal model, study design and body compartments measured. In contrast, all steady state comparative bioavailability studies in humans have shown no differences between synthetic and natural vitamin C, regardless of the subject population, study design or intervention used. Some pharmacokinetic studies in humans have shown transient and small comparative differences between synthetic and natural vitamin C, although these differences are likely to have minimal physiological impact. Study design issues and future research directions are discussed.
... In our laboratory, we have demonstrated that ascorbic acid in the presence of a natural citrus extract containing bioflavonoids was more absorbed than ascorbate alone in two studies; a long term guinea pig supplementation study [12] and a single 500 mg ascorbate dose in human subjects [13]. Therefore, we investigated the effectiveness of ascorbic acid and a citrus extract using the galactose-induced cataract model. ...
... Although not significant, there appears to be a greater lens ascorbate concentration in the CE groups compared to the corresponding AA groups. In a previous long-term ascorbate supplementation study with guinea pigs, CE produced a significantly greater liver and plasma ascorbate concentration than did AA [12]. ...
... However, from previous work, it is hypothesised that bioflavonoids stabilise the ascorbate preventing its oxidation to dehydroascorbate [23]. In addition, we have shown that bioflavonoids increase absorption of ascorbate in both guinea pigs and man [12,13]. Quercetin, a bioflavonoid, has been shown to inhibit the formation of sorbitol from glucose in intact rabbit lenses [24]. ...
A preliminary in vitro study demonstrated the significantly greater effectiveness of ascorbic acid in a citrus extract compared to ascorbic acid alone in diminishing the production of galacticol in rat lenses incubated in a high galactose media. Weanling rats were then given 10% galactose in their drinking water to induce cataracts. Ascorbic acid with or without citrus extract was also added to the drinking water of the experimental groups at 2 different concentrations. Ascorbic acid alone or in a citrus extract slowed the development, of cataracts in a dose-dependent fashion. The presence of citrus extract improved the efficacy of ascorbic acid especially at the lower dose. The greatest lens concentration of ascorbate was found in the groups given ascorbate and citrus extract. The combination of ascorbic acid and citrus extract are more effective than ascorbic acid alone as a supplement to increase lens ascorbate and slow down the progression of galactose cataracts.
... Vinson and Bose are the only investigators to have shown increased uptake of vitamin C, in the presence of citrus fruit extract, using a pharmacokinetic study design [27,28]. Their initial study, carried out in guinea pigs, indicated that vitamin C provided in a citrus fruit medium took longer to reach peak plasma concentrations compared with a synthetic vitamin C solution and also provided a larger area under the plasma ascorbate concentration-time curve [27]. ...
... Vinson and Bose are the only investigators to have shown increased uptake of vitamin C, in the presence of citrus fruit extract, using a pharmacokinetic study design [27,28]. Their initial study, carried out in guinea pigs, indicated that vitamin C provided in a citrus fruit medium took longer to reach peak plasma concentrations compared with a synthetic vitamin C solution and also provided a larger area under the plasma ascorbate concentration-time curve [27]. These investigators also observed a comparable trend in human subjects supplemented with 500 mg vitamin C in the presence or absence of a citrus fruit extract [28]. ...
Full-text available
Kiwifruit are a rich source of vitamin C and also contain numerous phytochemicals, such as flavonoids, which may influence the bioavailability of kiwifruit-derived vitamin C. The aim of this study was to compare the relative bioavailability of synthetic versus kiwifruit-derived vitamin C using a randomised cross-over pharmacokinetic study design. Nine non-smoking males (aged 18-35 years) received either a chewable tablet (200 mg vitamin C) or the equivalent dose from gold kiwifruit (Actinidia chinensis var. Sungold). Fasting blood and urine were collected half hourly to hourly over the eight hours following intervention. The ascorbate content of the plasma and urine was determined using HPLC with electrochemical detection. Plasma ascorbate levels increased from 0.5 h after the intervention (P = 0.008). No significant differences in the plasma time-concentration curves were observed between the two interventions (P = 0.645). An estimate of the total increase in plasma ascorbate indicated complete uptake of the ingested vitamin C tablet and kiwifruit-derived vitamin C. There was an increase in urinary ascorbate excretion, relative to urinary creatinine, from two hours post intervention (P < 0.001). There was also a significant difference between the two interventions, with enhanced ascorbate excretion observed in the kiwifruit group (P = 0.016). Urinary excretion was calculated as ~40% and ~50% of the ingested dose from the vitamin C tablet and kiwifruit arms, respectively. Overall, our pharmacokinetic study has shown comparable relative bioavailability of kiwifruit-derived vitamin C and synthetic vitamin C.
... Similar results obtained in studies on the individual ingredients of the Phytocee ™ are previously reported. [34][35][36] Interestingly Phytocee ™ could ameliorate LPO and increase the antioxidant enzymes comparable and much better than synthetic Vitamin C. Which may be attributed to the increased bioavailability of natural versus synthetic Vitamin C. [37,38] In addition to the studies on the antioxidant activities of individual ingredients of Phytocee ™ , the polyherbal formulation is also effi cacious against 2,2'-azobis [2-methyl propionamidine] dihydrochloride induced oxidative stress using HepG2 cells in vitro in cellular antioxidant assay. [12] Thus, our in vivo and in vitro study fi ndings on Phytocee ™ are correlated. ...
Full-text available
This study evaluated the antioxidant potential of a polyherbal formulation (Phytocee(™)) in the rodent model. Four groups of rats (n = 6) were pretreated with Vitamin C (20 mg/kg) or Phytocee(™) (20, 100, and 200 mg/kg), respectively for 10 days. Oxidative stress in rat liver was induced by administration of carbon tetrachloride (CCl4) at 2 ml/kg as a single dose orally to all groups except the vehicle control group. After 24 h of administration of CCl4, hepatic levels of malondialdehyde (MDA), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) levels were evaluated. Phytocee(™) administered groups at all the dose levels significantly reduced the hepatic MDA, serum ALT and AST levels with a marked increase in hepatic SOD and catalase as compared with CCl4 treated group. The findings suggest that Phytocee(™) markedly reversed the effects of CCl4 induced oxidative stress and can be used as an antioxidant feed supplement.
... These aforementioned mechanisms might plausibly be responsible for antioxidant activity of Phytocee™ Cool. Since, it is already established that ascorbic acid from natural sources is more potent antioxidant compared to synthetic vitamin C,[5758] Phytocee™ Cool can be used as a better substitute for synthetic vitamin C. Overall, Phytocee™ Cool is a unique combination of herbs and electrolytes that may contribute to alleviate the heat stress in birds; although the effect of electrolytes on the heat induced stress is yet to be explored. Thus, Phytocee™ Cool revealed its antioxidant effects by ameliorating oxidative stress induced changes and by modulating the activities of antioxidant defense systems. ...
Background: Antioxidants from natural sources have a major role in reversing the effects of oxidative stress and promoting health, growth and productivity in animals. Objective: This study was undertaken to investigate the possible antioxidant activity and hepatoprotective effects of Phytocee™ Cool on carbon tetrachloride (CCl4) induced oxidative stress and liver damage in rats. Materials and methods: Animals were pretreated with Phytocee™ Cool for 10 days and were challenged with CCl4 (1:1 v/v) in olive oil on the 10(th) day. After 24 h of CCl4 administration blood was collected and markers of hepatocellular damage aspartate aminotransferase (AST), alanine aminotransferase (ALT) were evaluated. Rats were sacrificed and oxidative stress in liver was estimated using malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase. Results: CCl4 caused a significant increase in serum AST, ALT, hepatic MDA and GSH levels, whereas the SOD and catalase activities were decreased. Phytocee™ Cool pretreatment attenuated the MDA, AST ALT levels and increased the activities of SOD and catalase. Conclusion: Phytocee™ Cool demonstrated antioxidant potential and hepatoprotective effects and plausibly be used in the amelioration of oxidative stress.
... The in vitro cytotoxic effects of synthetic 6-bromoisatin in this study could also be due to lower bioavailability of the pure compound to the cells when compared to the natural extract, which contains trace lipids that may help dissolve this lipophylic compound and/or facilitate interactions with cell membrane lipids. Previous studies have reported lower bioavailability of some synthetic compounds, in comparison with the naturally purified compounds [28,29]. For example, the bioavailability ratio of natural Vitamin E versus synthetic Vitamin E was shown to be close to 2:1 [29], which is similar to our study. ...
Full-text available
Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.
... The hypolipemic and antiaggregating effects of flavonoids have also been reviewed (Stavric and Matula, 1992). CE+AA has a high concentration of flavonoids (9.9%) and has been shown to increase the absorption of ascorbate in guinea pigs following long-term supplementation (Vinson and Bose, 1983). CE+AA and ascorbate, when given to normal subjects and smokers, significantly decreased plasma TBARS (Vinson and Hsu, 1992;. ...
Full-text available
A citrus extract containing flavonoids and ascorbic acid was used as a supplement to investigate its effect on lipids in hypercholesterolemic hamsters. Ascorbic acid or the flavonoids were without effect except that ascorbate did significantly raise HDL. After 1 month of feeding, the citrus extract plus ascorbic acid synergistically caused a significant reduction of 77%, 66%, and 40% in plasma total cholesterol, LDL + VLDL, and triglycerides, respectively, in comparison to the control group. The extract was also a synergistic inhibitor of in vitro cupric ion LDL + VLDL oxidation compared with ascorbic acid or the flavonoids alone. In a second 10-week hamster study, citrus extract plus ascorbate also significantly lowered plasma lipids, lipid peroxides, and ex vivo LDL + VLDL oxidizability vs a control group. Citrus extract plus ascorbate strongly inhibited atherosclerosis, and there was a significant correlation between several indices of oxidative susceptibility and atherosclerosis. Keywords: Lipids; atherosclerosis; flavonoids; lipid peroxidation; hamster
The experiment was conducted to determine the effect of dietary ascorbic acid supplementation on the accumulation of vitamin C in fish tissues. Total and dehydroascorbic acid were determined in larval and juvenile coregonids fed live Artemia salina nauplii and various commercial and laboratory-prepared compound foods. Total ascorbic acid decreased in the whole body of coregonids from approximately 122.8 μg g−1 wet weight before first feeding to 59.6 μg g−1 in 82 mg juveniles offered exclusively live food. In fish fed a diet deficient in vitamin C, the body ascorbate level decreased gradually to 12.5 μg g−1 within 1 month. In fish offered a diet containing 1483 μg ascorbate g−1 dry matter, the ascorbate level in the body decreased initially as fish weight increased up to 17 mg, but then rose again to 76 μg g−1 in fish of a mean body weight of 113 mg. It is concluded that after a few days of feeding, larval fish respond to ascorbic acid deficiency in the diet and thus the availability of ascorbate in their diet should be a matter of concern. It is suggested that the optimal dietary concentration of vitamin C is equivalent to that allowing the maintenance of “steady-state” tissue concentration in larval and juvenile fish.
Full-text available
Accurate methods for quantitatively measuring ascorbic acid and its derivatives are indispensable for probing the known and for discovering new functions of this vitamin. The most commonly used assays are summarized and their limitations characterized as they relate to biological samples in fish nutrition. Because ascorbic acid (AA) is extremely sensitive to degradation during processing and storage in fish diets, AA derivatives with sulfate (AS), phosphate (AP) or glucose (AG) at the C-2 position in the lactone ring have been used to increase its resistance to oxidation. We report data on the vitamin C availability in some of the derivatives based on in vitro hydrolysis experiments with fish enzymes. Enzyme-substrate affinity for enzymatic hydrolysis of ascorbyl mono-, tri- and poly-phosphates was different based on Km (mM) values of 1.18, 4.12 and 3.72, respectively. The experiments on in vivo absorption of AA and its derivatives revealed differences relating to the type of diet used (casein-gelatin or fishmeal based). In addition, they showed that AS apparent absorption was not significantly different from that of AA and AP in a practical diet for rainbow trout. We found that AS supplementation resulted in significantly lower concentrations of ascorbate in liver, kidney and intestine of rainbow trout and common carp than when AA was given. In experiments with rainbow trout broodstock, we found that the total ascorbate concentration in eggs from females fed an AA-free diet was significantly lower (82±32 μg·g−1) than in females fed an AP diet (316±43 μg·g−1). We concluded that there was no important storage form (AS or AP) in rainbow trout eggs independent of the dietary ascorbate source. Although suggestions have been made regarding AS function in fish as storage form, many are questionable because of the assay method used or because of speculative assumptions that AP may be converted to AS in fish tissues. In the final set of experiments with rainbow trout fry fed diets supplemented with AP, we demonstrated that tissue ascorbate concentration was maintained at a higher level even during depletion than in fish fed AA diets. In conjunction, the former had a much better chance of survival when exposed to a scorbutic diet devoid of vitamin C as a result of processing and/or storage.
Full-text available
This study was performed to determine whether synthetic ascorbic acid (AA) alone or in a natural citrus extract containing bioflavonoids, proteins, and carbohydrates was more bioavailable to human subjects. The effect of a single 500-mg ascorbate dose of the two forms and a placebo citrus extract on plasma ascorbate was examined in eight fasting subjects. A comparison of the areas under the plasma concentration-time curves showed that the citrus extract was 35% more absorbed than AA (p less than 0.001) and was more slowly absorbed than AA (p less than 0.001). In six ascorbate-saturated male subjects the ascorbate in the citrus extract produced a greater ascorbate excretion than AA alone in 24-h post-dose urine (p less than 0.05). Citrus extract ascorbate was less excreted than AA (p less than 0.05) in 12 nonsaturated subjects. Ascorbate in the citrus extract was found to be more bioavailable than AA alone in human subjects.
Intraluminal perfusion of the human small intestine has not been used extensively to study comparative bioavailability of vitamins. In this study a triple lumen tube with a 30-cm study segment was used to measure absorption of water-soluble vitamins from the human proximal jejunum. Fifteen normal subjects served as their own controls to quantitate absorption of folic acid and vitamin C from an orange juice solution and from a solution of synthetic vitamins. Despite a predictably greater water absorption from the glucose containing orange juice solution, the absorption of the two water-soluble vitamins did not differ significantly from the two solutions. Natural and synthetic ascorbate and folate were avidly absorbed in the first 30 cm of jejunum and with the exception of synthetic folate correlated positively with water absorption. This method, previously applied to the absorption of sugars, amino acids, and electrolytes, can be reliably applied to the study of comparative bioavailability of nutrients from food sources. The advantages of triple lumen perfusion over previous methods are: 1) it overcomes the necessity for urine collections in metabolic studies, 2) it can be used to study sites and mechanism of absorption, and 3) it is a direct measurement of absorption capacity.
The effect of penta-, hexa- and heptamethoxyflavones from citrus fruits was determined on the ESR of 48 apparently healthy subjects selected at random. The ESR was reduced 78.8% by the pentamethoxyflavone (sinensetin), 70.8% by the hexamethoxyflavone (nobiletin) and 63.9% by the heptamethoxyflavone (heptamethoxyflavone) at a concentration of 48 μM/l of blood or 17.9, 19.3 and 20.8 mcg per ml of blood, respectively. The evidence indicates that flavonoids act to maintain suspension of the formed elements in plasma, thereby inhibiting the apparent spontaneous blood cell adhesion occurring in normal subjects and the increased blood cell clumping accompanying disease, trauma and stress. A dietary role for flavonoids is suggested by evidence of a widespread low level blood cell aggregation in apparently healthy subjects, which is inhibited by flavonoids that are normal components of certain foods. The significance of blood cell aggregation is that it interferes with the microcirculation causing a variety of adverse effects and promotes thrombosis and embolism of large vessels.
The efficacy of synthetic ascorbic acid has been questioned. In this paper the natural and synthetic forms are evaluated in men by measuring serum and leucocyte levels and urinary excretion before and after saturation.