Bleeding tendency and ascorbic acid requirements: systematic review and meta-analysis of clinical trials

Abstract

Context The World Health Organization set the recommended daily vitamin C intake, henceforth referred to as ascorbic acid (AA), on the basis of scurvy prevention. Double-blind AA depletion-repletion studies suggest that this recommended AA dose may be too low to prevent microvascular fragility. Objectives (1) To conduct a systematic review and meta-analysis of controlled clinical trials on whether AA supplementation leads to a reduced gingival bleeding tendency, a manifestation of microvascular fragility; and (2) to relate AA plasma levels to retinal hemorrhaging, another manifestation of microvascular fragility. Data sources Data were reviewed from 15 trials conducted in 6 countries with 1140 predominantly healthy participants with measures of gingival bleeding tendency, and from the National Health and Nutrition Examination Survey (NHANES) III of 8210 US residents with measures of retinal hemorrhaging. Results In clinical trials, AA supplementation reduced gingival bleeding tendency when estimated baseline AA plasma levels were < 28 μmol/L (standardized mean difference [SMD], −0.83; 95%CI, −1.16 to −0.49; P < 0.002). Supplementation with AA did not unequivocally reduce gingival bleeding tendency when baseline estimated AA plasma levels were >48 μmol/L or unknown (respective standardized mean differences: −0.23, 95%CI, −0.45 to −0.01, P < 0.05; and −0.56; 95%CI: −1.19 to 0.06, P < 0.08). In NHANES III, prevalence of both retinal hemorrhaging and gingival bleeding tendency increased when AA plasma levels were within the range that protects against scurvy (11–28 μmol/L; respective prevalence ratios adjusted for age and sex: 1.47; 95%CI: 1.22–1.77; and 1.64; 95%CI: 1.32–2.03; P < 0.001 for both). Conclusion Consistent evidence from controlled clinical trials indicates that setting human AA requirements based on scurvy prevention leads to AA plasma levels that may be too low to prevent an increased gingival bleeding tendency. Gingival bleeding tendency and retinal hemorrhaging coincide with low AA plasma levels and thus may be reflective of a systemic microvascular pathology that is reversible with an increased daily AA intake.

Vitamin C for sepsis intervention: from redox biochemistry to clinical medicine

“…The other enzymes for which vitamin C acts as a cofactor are involved in carnitine synthesis, catecholamine synthesis, peptide amidation, and tyrosine metabolism [28]. Due to its essential role in collagen biosynthesis, deficiency of vitamin C compromises the integrity of blood vessels, leading to scorbutic gums and pinpoint hemorrhage, characteristic manifestations of vitamin C deficiency [32].…”

How a Nutritional Deficiency Became Treated with Fluoride

“…The National Academy of Medicine described an increased gingival bleeding tendency as one of the most sensitive markers for a vitamin C deficiency in 2000 [95]. Clinical trials focusing on bleeding tendency confirmed these conclusions [96]. Nevertheless, the conventional wisdom is to largely ignore a vitamin C deficiency in the etiology of gingival bleeding.…”

On the Pathogenicity of the Oral Biofilm: A Critical Review from a Biological, Evolutionary, and Nutritional Point of View

“…This aim seems as unrealistic as uncausal, as proven by the discrepancy between the already high level of oral hygiene efforts of industrialized populations and the still remaining high prevalence of oral diseases. Furthermore, if the causes of these diseases may lie in other factors than plaque, plaque control would accordingly only be a symptomatic approach that would blur the symptoms but not the underlying causal factor [ 21 , 22 ]. This implies at least two harmful or detrimental consequences for personal and even public health care: the primary bodily “warning signal” in the form of gingivitis, e.g., as a consequence of excessive sugar consumption or micronutrient deficiency, would not lead to a cause-related therapy (sugar cessation or supply of micronutrients) but to a symptomatic plaque reduction [ 21 , 22 , 23 ].…”

“…Furthermore, if the causes of these diseases may lie in other factors than plaque, plaque control would accordingly only be a symptomatic approach that would blur the symptoms but not the underlying causal factor [ 21 , 22 ]. This implies at least two harmful or detrimental consequences for personal and even public health care: the primary bodily “warning signal” in the form of gingivitis, e.g., as a consequence of excessive sugar consumption or micronutrient deficiency, would not lead to a cause-related therapy (sugar cessation or supply of micronutrients) but to a symptomatic plaque reduction [ 21 , 22 , 23 ]. While the gingivitis would get better, the malnutrition would not and may lead to further diseases (e.g., overweight or retinal hemorrhaging).…”