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Vitamin C Dietary Supplements: An Objective Review of the Clinical Evidence. Part II
Abstract
Arguably, vitamin C has received more attention clinically and commercially compared to any other dietary supplement. The strongest data for vitamin C appears to be as a nutrient that potentially enhances a combination product, and this has been observed in the areas of prenatal care, eye disease, general health maintenance, and immune enhancement. However, the possibility also exists that vitamin C by itself may favorably impact these conditions. Additionally, vitamin C containing metabolites (Ester-C) already has several clinical studies that suggest it may provide better tolerance, immune enhancement of greater duration, and a lower risk of side effects compared to ascorbic acid (vitamin C) alone. Our group is currently comparing vitamin C by itself to Ester-C in various clinical studies, which should determine the impact of this nutrient on a variety of important immune measurements, as well as markers of stress-induced immune changes.
... It is biosynthesized by almost all organisms except humans. It is widely known as the vitamin whose deficiency causes scurvy in humans (Li, Byers, and Walvekan 2008; Velandia et al. 2008; Moyad and Combs 2007). Biotin, also known as vitamin H or B 7 (coenzyme R, Biopeiderm; Fig. 1 ...
Fourier transform-infrared (FT-IR) spectrometry was used for the rapid, direct measurement of ascorbic acid (vitamin C) and biotin (vitamin H) in different pharmaceutical products. Conventional KBr spectra were compared for the best determination of active substances in drug preparations. The Beer-Lambert law and chemometric approaches were applied in data processing.
Arguably, vitamin C has received more attention clinically and commercially compared with any other dietary supplement. First recognized as a way to eliminate scurvy and infections related to scurvy, recent studies utilizing this compound in a range of formulations and by itself show that it potentially may impact the risk of cancer, heart disease, and other diverse conditions. However, what is the actual current clinical evidence for this vitamin or another formulation of this vitamin? The strongest data for vitamin C appear to be as a nutrient that potentially enhances a combination product and this has been observed in the areas of prenatal care, eye disease, and general health maintenance. However, the possibility also exists that vitamin C by itself may favorably impact these conditions. For example, the potential for immune enhancement for users of vitamin C supplements alone is of interest. A recent meta-analysis of randomized trials published over the past several decades concluded that the evidence was preliminary but solid enough to consider recommending vitamin C supplementation to prevent and help treat pneumonia along with conventional medicine in some cases. The Physicians' Health Study II, which is randomizing 15,000 doctors to several types of supplements, including 500 mg of vitamin C daily or placebo, will be one of the most interesting clinical studies to date with this nutrient in terms of preventing a variety of chronic diseases. Additionally, Vitamin C containing metabolites (Ester-C) already has several clinical studies that suggest it may provide better tolerance, immune enhancement of greater duration, and a lower risk of side effects compared with ascorbic acid (vitamin C) alone. Our group is currently designing and recruiting one of the largest clinical studies of vitamin C by itself compared with Ester-C. These clinical studies should determine the impact of this nutrient on a variety of important immune measurements, as well as whether it has the potential to reduce mental and physical markers of stress-induced immune changes. Regardless, vitamin C is establishing a clinical track record, which is allowing researchers to begin to understand its overall impact in medicine apart from its antiquated role as a solution for scurvy.
The objective of this study was to test the effects of acute doses of vitamin C alone, calcium ascorbate with vitamin C metabolites, and placebo, on total plasma and leukocyte vitamin C concentrations over 24 hours.
A double-blind, placebo-controlled, four-way crossover study was performed consisting of four separate phases lasting 24 hours each and utilizing one of four oral 1000-mg preparations within each phase (one of vitamin C alone, two separate vitamin C formulations of calcium ascorbate with vitamin C metabolites, and placebo). There was a 7-day washout between phases, and blood draws at seven time points within each phase of the study for a total of 28 serologic measurements per subject and 420 total measurements for the entire clinical trial. Vitamin C concentration in plasma and leukocytes were measured by high-performance liquid chromatography at baseline and at six sequential time periods over 24 hours.
Fifteen healthy males were enrolled, aged 18-39 years; nine were had never smoked and six were chronic smokers. No significant difference in plasma vitamin C levels was observed when comparing the different preparations. However, at 24 hours, calcium ascorbate with metabolites resulted in significantly higher concentrations of vitamin C in leukocytes (P<0.0001) compared with vitamin C alone. These results were similar for both metabolite formulations, and independent of smoking status.
Regardless of smoking status, vitamin C metabolites may enhance leukocyte utilization of vitamin C itself, despite no consistent difference in plasma levels among the different preparations. A larger clinical investigation is warranted to confirm these preliminary findings, and to determine the clinical relevance of this impact on overall immune function.
Background:
Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss.
Objective:
To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.
Design:
The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo.
Main outcome measures:
(1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (> or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.
Results:
Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations.
Conclusions:
Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.
A prospective, randomized, double-blind study was carried out to determine whether vitamin C prophylaxis, 2.0 g/day, vs placebo prophylaxis would reduce the incidence or morbidity of the common cold and other respiratory illnesses in 674 marine recruits during an eight-week period. Whole-blood ascorbic acid levels measured six weeks after initiation of the study were significantly higher in the vitamin C group. There was no difference between the two groups in the incidence or duration of colds. The vitamin C group rated their colds as being less severe, but this was not reflected in different symptom complexes or in fewer sick-call visits or training days lost. This study and the literature do not support the prophylactic use of vitamin C to prevent the common cold.
Recommendations for vitamin C intake are under revision by the Food and Nutrition Board of the National Academy of Sciences. Since 1989 when the last recommended dietary allowance (RDA) of 60 mg was published, extensive biochemical, molecular, epidemiologic, and clinical data have become available. New recommendations can be based on the following 9 criteria: dietary availability, steady-state concentrations in plasma in relationship to dose, steady-state concentrations in tissues in relationship to dose, bioavailability, urine excretion, adverse effects, biochemical and molecular function in relationship to vitamin concentration, direct beneficial effects and epidemiologic observations in relationship to dose, and prevention of deficiency. We applied these criteria to the Food and Nutrition Board's new guidelines, the Dietary Reference Intakes, which include 4 reference values. The estimated average requirement (EAR) is the amount of nutrient estimated to meet the requirement of half the healthy individuals in a life-stage and gender group. Based on an EAR of 100 mg/d of vitamin C, the RDA is proposed to be 120 mg/d. If the EAR cannot be determined, an adequate intake (AI) amount is recommended instead of an RDA. The AI was estimated to be either 200 mg/d from 5 servings of fruits and vegetables or 100 mg/d of vitamin C to prevent deficiency with a margin of safety. The final classification, the tolerable upper intake level, is the highest daily level of nutrient intake that does not pose risk or adverse health effects to almost all individuals in the population. This amount is proposed to be less than 1 g of vitamin C daily. Physicians can tell patients that 5 servings of fruits and vegetables per day may be beneficial in preventing cancer and providing sufficient vitamin C intake for healthy people, and that 1 g or more of vitamin C may have adverse consequences in some people.
One hundred sixty-eight volunteers were randomized to receive a placebo or a vitamin C supplement, two tablets daily, over a 60-day period between November and February. They used a five-point scale to assess their health and recorded any common cold infections and symptoms in a daily diary. Compared with the placebo group, the active-treatment group had significantly fewer colds (37 vs 50, P<.05), fewer days challenged virally (85 vs 178), and a significantly shorter duration of severe symptoms (1.8 vs 3.1 days, P<.03). Consequently, volunteers in the active group were less likely to get a cold and recovered faster if infected. Few side effects occurred with the active treatment, and volunteers reported greatly increased satisfaction with the study supplement compared with any previous form of vitamin C. This well-tolerated vitamin C supplement may prevent the common cold and shorten the duration of symptoms. Volunteers were generally impressed by the protection afforded them during the winter months and the general acceptability of the study medication.
For more than 50 years, the Food and Nutrition Board of the National Academy of Sciences has been reviewing nutrition research and defining nutrient requirements for healthy people, referred to as the Recommended Dietary Allowances (RDA). As new nutrition research is published, the importance of vitamins as vital nutrients is underscored, and new physiologic roles and applications to human health are examined and considered with regard to updating the RDA. Each year a substantial amount of new research is published on vitamins. This review examines recent research published on the importance of vitamin C with regard to general health.
Vitamin deficiencies are frequent in children suffering from malaria. The effects of maternal multivitamin supplementation on the risk of malaria in children are unknown. We examined the impact of providing multivitamins or vitamin A/beta-carotene supplements during pregnancy and lactation to HIV-infected women on their children's risk of malaria up to 2 years of age, in a randomized, placebo-controlled trial. Tanzanian women (N = 829) received one of four daily oral regimens during pregnancy and after delivery: 1) vitamins B, C, and E (multivitamins); 2) vitamin A and beta-carotene (VA/BC); 3) multivitamins including VA/BC; or 4) placebo. After 6 months of age, all children received 6-monthly oral vitamin A supplements irrespective of treatment arm. The incidence of childhood malaria was assessed through three-monthly blood smears and at monthly and interim clinic visits from birth to 24 months of age. Compared with placebo, multivitamins excluding VA/BC reduced the incidence of clinical malaria by 71% (95% CI = 11-91%; P = 0.02), whereas VA/BC alone resulted in a nonsignificant 63% reduction (95% CI = -4% to 87%; P = 0.06). Multivitamins including VA/BC significantly reduced the incidence of high parasitemia by 43% (95% CI = 2-67%; P = 0.04). The effects did not vary according to the children's HIV status. Supplementation of pregnant and lactating HIV-infected women with vitamins B, C, and E might be a useful, inexpensive intervention to decrease the burden of malaria in children born to HIV-infected women in sub-Saharan Africa.
Vitamin C is required for collagen synthesis and biosynthesis of certain hormones and recommended dietary intake levels are largely based these requirements. However, to function effectively as an antioxidant (or a pro-oxidant), relatively high levels of this vitamin must be maintained in the body. The instability of vitamin C combined with its relatively poor intestinal absorption and ready excretion from the body reduce physiological availability of this vitamin. This inability to maintain high serum levels of vitamin C may have serious health implications and is particularly relevant in the onset and progression of degenerative disease, such as cancer and cardiovascular disease (CVD), which have a strong contributing oxidative damage factor. In this review, we examine recent studies on the regulation of transport mechanisms for vitamin C, related clinical ramifications, and potential implications in high-dose vitamin C therapy. We also evaluate recent clinical and scientific evidence on the effects of this vitamin on cancer and CVD, with focus on the key mechanisms of action that may contribute to the therapeutic potential of this vitamin in these diseases. Several animal models that could be utilized to address unresolved questions regarding the feasibility of vitamin C therapy are also discussed.
The Osteogenic Disorder Shionogi (ODS) rat, Clea Inc., Tokyo, Japan lacks the ability to synthesize L-ascorbic acid (AA). As with man, monkey and the guinea pig, this rat lacks L-gulonolactone oxidase necessary for the synthesis of AA from glucose. This study shows this animal to be an alternative to the guinea pig in AA studies. The anti-scorbutic potency of Ester C (EC), a calcium ascorbate and calcium threonate mixture, was compared with an AA dose of equal ascorbate activity equivalents (AAE) for anti-scorbutic activity in the ODS rat. The minimal anti-scorbutic dose of EC was determined to be 0.44 mg/kg/day (AAE), while an AA dose of 0.51 mg/kg/day (AAE) was not anti-scorbutic in a 24 day study. At 24 days EC rats gained 125% of initial body weight (BW) and the AA rats only 45% BW. Scorbutic signs at 24 days were scored on a 0 (min) to 3 (max) scale. The EC/AA ratio scores were: hemorrhage 0/1.4, behavior change 0/2.0, piloerection 0/2.2, mobility 0.4/2.2, dysbasia 0.6/2.8 and ataxia 0.4/1.0. Pearson's correlation coefficient for BW versus AAE was r = .34 for the AA group and r = .90 for the EC group. The morbidity index for EC was 0/5 and for the AA group 2/5. The AAE dose of AA which was 16% higher/day than the EC AAE dose was not anti-scorbutic, while the EC dose was anti-scorbutic. EC rats had 3.5X greater weight gain, a sensitive indicator of scurvy, than the AA rats. EC rats had 3-4 times less, if any, scorbutic signs than AA rats. The results clearly show that, based on ascorbate activity equivalents, EC has more available ascorbate activity/potency than AA. The mechanism of this increased potency is believed to be due to the facilitated transport of AAE into the cell by the threonate (a normal in vivo metabolite of AA) present in the EC product. In addition, previous studies have shown EC (AAE) to be higher in plasma and excreted less rapidly than the AAE derived from AA administered orally.
The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial of primary prevention designed to assess the effects of low-dose aspirin on cardiovascular disease and of beta-carotene on risks of cancer. A total of 22,071 U.S. male physicians 40 to 84 years of age were randomized to one of four treatment groups: active aspirin and active beta-carotene, active aspirin and beta-carotene placebo, aspirin placebo and active beta-carotene, or both placebos. Whereas the beta-carotene component of the trial is ongoing, the blinded aspirin component was terminated early primarily because of a statistically extreme benefit of aspirin on first myocardial infarction. We obtained data relating to a large number of variables, including demographics, personal medical history, family history, health habits, and diet before randomization and compared them among the four treatment groups. As expected in a randomized trial of this sample size, the distribution of baseline characteristics was virtually identical among the treatment groups. This comparison indicates certainly no confounding by the baseline variables that were collected and suggests that other unmeasured or unknown potential confounders are also likely to be distributed evenly between the treatment groups. Thus, any observed differences in outcome between these groups likely result from the effects of the treatments themselves.
The effects of preincubation of human T-lymphoma cells with increasing concentrations of calcium L-threonate on the uptake of L-[1-14C]ascorbic acid were examined. Calcium L-threonate (0-1,000 mg%) stimulated ascorbic acid (1.25 mg%) uptake in a dose-dependent manner. These results indicate that calcium threonate and possibly other ascorbic acid metabolites have biological activity and potential pharmacological applications.
A recent survey of foods that constitute the major sources of vitamin C in the American diet yielded information on the total content of this vitamin as well as the amount of its two forms, ascorbic acid and dehydroascorbic acid (DHAA) in these foods. Samples of individual foods showed a surprising large range of vitamin content even for foods collected from the same regions of the country and from the same source. The amount of DHAA in the different foods varied from approximately 10% to 20% of the total vitamin content. The large range of values for the vitamin content in a given food suggests further that in human-diet studies, when the major sources of vitamin C are from a few foods, daily analyses are required for the necessary precision.
This article has no abstract; the first 100 words appear below.
ASCORBIC acid, originally called vitamin C, is required for human health.¹ In human beings deprived of ascorbic acid, the deficiency disease scurvy develops and can be life threatening. Although a disease remarkably similar to scurvy was described by the ancient Egyptians,²,³ it was not until 1753 that a Scottish physician, James Lind, systematically described scurvy and its prevention by dietary means.⁴ Even then, the dietary requirements were controversial. For four decades the British navy refused to accept Lind's findings, and countless sailors continued to die unnecessarily from scurvy until lemon juice was finally included in sailors' rations. Research since Lind's . . .
I am indebted to David Blank for editorial assistance, to Gordon Cutler for encouragement, and to Shelley Sturman and Harvey Pollard in particular for helpful suggestions and consistent wholehearted support.
Source Information
From the Laboratory of Cell Biology and Genetics, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md. Address reprint requests to Dr. Levine at Bldg. 4, Rm. 312, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892.
Cytophotoelectrometric analysis and biochemical estimations of ascorbic acid were carried out in various mammalian tissues.1.2. Significant variations were found in the level of ascorbic acid in different tissues. The highest ascorbic acid content per cell was observed in the adrenal medulla and the least in the pancreatic islets.2.3. Cytophotoelectrometric determinations of ascorbic acid agreed closely with those obtained by biochemical estimations.3.4. On the basis of the results it is postulated that ascorbic acid functions as an electron donor in metabolic reactions of these tissues via the formation of its free radical.
The concentration of ascorbic acid in leukocytes, adrenals, brain, spleen, and heart of growing male guinea pigs was investigated after the animals had received daily oral injections of l-ascorbic acid ranging from 0.2 to 10.0 mg/100 g body weight for 42 days while being maintained on an ascorbic acid-free semipurified diet. The concentration of ascorbic acid in leukocytes and organs increased most rapidly with increasing oral intake of the vitamin until the animals’ requirement was reached. The dose-response curves were similar in shape for ascorbic acid in leukocytes and the organs, a similarity which was confirmed by high correlation coefficients. The results indicated that leukocytes reflect tissue concentration and hence vitamin C status in growing guinea pigs.
A randomised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections (bronchitis and bronchopneumonia). Patients were assessed clinically and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day, or placebo. This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection. Using a clinical scoring system based on major symptoms of the respiratory condition, patients supplemented with the vitamin fared significantly better than those on placebo. This was particularly the case for those commencing the trial most severely ill, many of whom had very low plasma and white cell vitamin C concentrations on admission. Various mechanisms by which vitamin C could assist this type of patient are discussed.
1. Previously, we reported that calcium L-threonate caused a dose-related increase in uptake of ascorbic acid (AA) by human T-lymphoma cells. Preincubation of mouse fibroblasts with calcium L-threonate also resulted in a dose-related augmentation in uptake of AA as compared to non-treated controls. 2. Potassium L-lyxonate increased AA uptake by lymphoma cells, but did not significantly affect uptake by fibroblasts. Tartaric acid decreased uptake of AA by both cell lines. 3. Ouabain and dinitrophenol had no effect on AA uptake nor on the ability of threonate to augment AA uptake by fibroblasts. However, in T-lymphoma cells ouabain and dinitrophenol reduced AA uptake and prevented augmentation of AA uptake by calcium L-threonate.
2President of Lyda Associates, Inc., Palisades, NY and adjunct professor at Columbia University School of Public Health, New York, NY.
The clinical description of scurvy is well recorded in the history of medicine. Yet, because scurvy is relatively uncommon in industrially developed countries, it is often underdiagnosed, and unnecessary tests are performed. The result of a prolonged deficiency of ascorbic acid, scurvy is classically manifested by perifollicular hemorrhages, corkscrew hairs, large ecchymoses and hemorrhagic gingivitis. Although the disease is considered uncommon in the United States, two populations at greatest risk--the institutionalized elderly and alcoholics--are increasing.
It is of interest that, aside from starvation, the nutrition catastrophes of the past, including scurvy (vitamin C deficiency) resulting from lack of fresh vegetables and fruit and beriberi (vitamin B1 deficiency) from consumption of polished rice, are forgotten and only of interest as history. The problems of vitamins were largely considered settled by the 1950s. With the appearance on the market of multiple-vitamin-and-mineral tablets, the public was also satisfied and considered the problem of deficiencies solved. Now we are faced with unexpected nutrition problems primarily in the industrial West, which follow from the excess of dietary fats, the refining of grains to make white flour, and the alteration of other natural foods for general use. As we labor to understand and control these problems, new and unexpected "toxins," deficiencies, or excesses may develop. This article is a brief historical account of the past based largely on personal experiences and my concern for the future. The realization that the Western industrial world's high-fat diet was profoundly unhealthy has led to an attempt at correction by development of numerous low-fat foods. Unsaturated vegetable oils and saturated animal fats are being reduced or eliminated. In their place, other components and compounds are being substituted for their taste and consistency, without adequate concern for their nutritional value or freedom from toxicity. Before continuing this risk, the health of the world's population must be considered. Our past experiences with chemical and mechanical alteration of foods, and its effect on the nutrition of every man, woman, and child in the Western world, primarily in industrial North America, should not be forgotten.
The widespread prevalence of diet-related health problems, particularly in highly industrialized nations, suggests that many humans are not eating in a manner compatible with their biology. Anthropoids, including all great apes, take most of their diet from plants, and there is general consensus that humans come from a strongly herbivorous ancestry. Though gut proportions differ, overall gut anatomy and the pattern of digestive kinetics of extant apes and humans are very similar. Analysis of tropical forest leaves and fruits routinely consumed by wild primates shows that many of these foods are good sources of hexoses, cellulose, hemicellulose, pectic substances, vitamin C, minerals, essential fatty acids, and protein. In general, relative to body weight, the average wild monkey or ape appears to take in far higher levels of many essential nutrients each day than the average American and such nutrients (as well as other substances) are being consumed together in their natural chemical matrix. The recommendation that Americans consume more fresh fruits and vegetables in greater variety appears well supported by data on the diets of free-ranging monkeys and apes. Such data also suggest that greater attention to features of the diet and digestive physiology of non-human primates could direct attention to important areas for future research on features of human diet and health.
Vitamin C or ascorbate is important in wound healing due to its essential role in collagen synthesis. To study wound healing in the periodontium, cells adherent to expanded polytetrafluoroethylene (ePTFE) augmentation membranes, recovered from edentulous ridge augmentation procedures, have been established in culture in our laboratories. The objective of this study was to determine whether treatment of these cells with a calcium ascorbate, which contains vitamin C metabolites (metabolite-supplemented ascorbate), would increase the production of collagenous protein and mineralized tissue in vitro, as compared to unsupplemented calcium ascorbate (ascorbate).
Cells derived from ePTFE membranes were cultured with beta-glycerophosphate and the test agents for 2 to 5 weeks, and the surface areas of the cell cultures occupied by mineralized nodules were measured using computerized image analysis. One experiment tested the effects of calcium threonate, one of the vitamin C metabolites in metabolite-supplemented ascorbate. Incorporation of radioactive proline and glycine was used as a measure of total protein (radioactivity precipitated by trichloracetic acid) and collagenase-digestible protein (radioactivity released by collagenase digestion.) Co-localization of collagen and fibronectin was examined by immunofluorescence.
In vitro treatment of these cells with metabolite-supplemented ascorbate increased the area of the cell cultures occupied by mineralized nodules after 5 weeks. Cell cultures treated with metabolite-supplemented ascorbate also exhibited significant increases in total protein. The increase in collagenous proteins in these cultures accounted for 85% of the increase in total protein. The greatest difference between treatment groups was observed in the cell-associated fraction containing the extracellular matrix. The additional collagen exhibited normal co-distribution with fibronectin. In cultures treated with ascorbate spiked with calcium threonate, the area of mineralized tissue was significantly greater than in ascorbate-treated cultures, but was less than that observed in cultures treated with metabolite-supplemented ascorbate.
In vitro treatment with ascorbate containing vitamin C metabolites enhanced the formation of mineralized nodules and collagenous proteins. Calcium threonate may be one of the metabolites influencing the mineralization process. Identifying factors which facilitate the formation of mineralized tissue has significant clinical ramifications in terms of wound healing and bone regeneration.
The goal of this randomized, double-blind crossover clinical trial in 50 healthy volunteers sensitive to acidic foods was to evaluate whether Ester-C calcium ascorbate causes fewer epigastric adverse effects than are produced by regular ascorbic acid (AA). Volunteers were randomly separated into 2 groups of 25. The study comprised an observation period of 9 days (phase 1 medication for 3 consecutive days, washout phase for 3 consecutive days, phase 2 medication for 3 consecutive days). Participants took 1000 mg vitamin C as Ester-C during phase 1 of the study followed by 1000 mg of vitamin C as AA during phase 2, or vice versa. During the course of the study, 3 examinations for the evaluation of epigastric adverse effects were performed (on days 0, 3, and 9). Participants used a diary to record epigastric adverse effects on a daily basis. In total, 28 (56%) of 50 participants reported 88 epigastric adverse effects of mild to moderate intensity. Of these 88 adverse effects, 33 (37.5%) occurred after intake of Ester-C and 55 (62.5%) were noted after intake of AA. The tolerability of Ester-C was rated "very good" by 72% of participants, whereas AA was rated "very good" by only 54%. This difference is statistically significant (P<.05). Investigators concluded that Ester-C compared with AA caused significantly fewer epigastric adverse effects in participants sensitive to acidic foods and that Ester-C is much better tolerated.
Estrogens, apart from their classic role as steroid hormones, also possess significant antioxidant properties. The present study was undertaken to assess the antioxidant potential of the female during the various menstrual phases and to investigate the correlation between ascorbic acid, dehydroascorbic acid plasma levels, total antioxidant plasma status, and estradiol levels.
Thirteen eumenorrhoic women were studied. Ascorbic acid and dehydroascorbic acid plasma levels, total antioxidant plasma status, estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone during time of menstruation, midfollicular phase, time of ovulation, and midluteal phase were determined. Ascorbic-dehydroascorbic acid ratio was also calculated.
A progressive significant rise in ascorbic acid plasma levels (p < 0.01), ascorbic-dehydroascorbic acid ratio (p < 0.001), and total antioxidant plasma status (p < 0.05) from menstruation to ovulation was observed. Moreover, a significant decrease in dehydroascorbic acid was found at the same phases (p < 0.05). Changes of estradiol levels during the menstrual cycle correlated positively with the changes of ascorbic acid levels and total antioxidant plasma status (p < 0.05). Furthermore, estradiol levels correlated positively with ascorbic acid levels (p < 0.05, r < 0.5), ascorbic-dehydroascorbic acid ratio (p < 0.05, r < 0.5), and total antioxidant plasma status (p < 0.05, r < 0.8) in all menstrual phases.
An elevated antioxidant protection during ovulation and the midluteal phase appears to be present in eumenorrhoic women. Moreover we observed a cyclic variation in the antioxidant parameters we assayed in the females in the present study, which could be due to cyclic changes in estradiol levels.
Although much decreased in prevalence, scurvy still exists in industrialized societies. Few recent large studies have examined its pathogenesis, signs, and symptoms.
After we diagnosed scurvy in a 77-year-old female patient in 2003, we conducted a retrospective records review to identify patients with scurvy treated between 1976 and 2002 at Mayo Clinic (Scottsdale, Arizona; Rochester, Minnesota; or Jacksonville, Florida). We also searched the English-language medical literature for published reports on scurvy.
In addition to our patient, seven of 11 patients whose records in the institutional database mentioned vitamin C deficiency were women. The age ranged from a neonate to 77 years (mean, 48 years). The most common associated causes were concomitant gastrointestinal disease, poor dentition, food faddism, and alcoholism. Vitamin or mineral deficiencies other than vitamin C deficiency were also found in our patients who had scurvy. The most common symptoms were bruising, arthralgias, or joint swelling. The most common signs were pedal edema, bruising, or mucosal changes. Four patients had vague symptoms of myalgias and fatigue without classic findings, and five had concomitant nutritional deficiencies. Follow-up available for six of 12 patients treated by vitamin C supplementation showed complete resolution of symptoms in five.
Patients with scurvy may present with classic symptoms and signs or with nonspecific clinical symptoms and an absence of diagnostically suggestive physical findings. Concomitant deficiency states occur not uncommonly. Taking a thorough dietary history and measuring serum ascorbic acid levels should be considered for patients with classic signs and symptoms, nonspecific musculoskeletal complaints, or other vitamin or mineral deficiencies.
Complex regional pain syndrome type I is treated symptomatically. A protective effect of vitamin C (ascorbic acid) has been reported previously. A dose-response study was designed to evaluate its effect in patients with wrist fractures.
In a double-blind, prospective, multicenter trial, 416 patients with 427 wrist fractures were randomly allocated to treatment with placebo or treatment with 200, 500, or 1500 mg of vitamin C daily for fifty days. The effect of gender, age, fracture type, and cast-related complaints on the occurrence of complex regional pain syndrome was analyzed.
Three hundred and seventeen patients with 328 fractures were randomized to receive vitamin C, and ninety-nine patients with ninety-nine fractures were randomized to receive a placebo. The prevalence of complex regional pain syndrome was 2.4% (eight of 328) in the vitamin C group and 10.1% (ten of ninety-nine) in the placebo group (p=0.002); all of the affected patients were elderly women. Analysis of the different doses of vitamin C showed that the prevalence of complex regional pain syndrome was 4.2% (four of ninety-six) in the 200-mg group (relative risk, 0.41; 95% confidence interval, 0.13 to 1.27), 1.8% (two of 114) in the 500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.77), and 1.7% (two of 118) in the 1500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.75). Early cast-related complaints predicted the development of complex regional pain syndrome (relative risk, 5.35; 95% confidence interval, 2.13 to 13.42).
Vitamin C reduces the prevalence of complex regional pain syndrome after wrist fractures. A daily dose of 500 mg for fifty days is recommended.
Vitamin C content of foods
- Vanderslice