Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, Washington, USA.
Nutr Rev. 2021 Aug 9;79(9):964-975. doi: 10.1093/nutrit/nuaa115.
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.
(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 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.
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).
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.
世界卫生组织（WHO）根据坏血病的预防来设定每日维生素 C 摄入量，即抗坏血酸（AA）的推荐量。双盲 AA 耗竭-补充研究表明，这一推荐剂量可能过低，无法预防微血管脆弱。
（1）系统综述和荟萃分析对照临床试验，以评估 AA 补充是否会降低牙龈出血倾向，这是微血管脆弱的表现；（2）将 AA 血浆水平与视网膜出血联系起来，视网膜出血也是微血管脆弱的另一种表现。
数据来自 6 个国家的 15 项试验，共有 1140 名主要健康参与者，通过测量牙龈出血倾向来评估微血管脆弱，以及来自美国国家健康和营养调查（NHANES）III 的 8210 名美国居民的数据，通过测量视网膜出血来评估微血管脆弱。
在临床试验中，当基线 AA 血浆水平<28μmol/L 时，AA 补充可降低牙龈出血倾向（标准化均数差 [SMD]，-0.83；95%CI，-1.16 至 -0.49；P<0.002）。当基线 AA 血浆水平>48μmol/L 或未知时，AA 补充并未明确降低牙龈出血倾向（分别的标准化均数差：-0.23，95%CI，-0.45 至 -0.01，P<0.05；-0.56；95%CI：-1.19 至 0.06，P<0.08）。在 NHANES III 中，当 AA 血浆水平处于预防坏血病的范围（11-28μmol/L）时，视网膜出血和牙龈出血倾向的患病率均增加（年龄和性别调整后的患病率比：1.47；95%CI，1.22-1.77；和 1.64；95%CI，1.32-2.03；两者均 P<0.001）。
对照临床试验的一致证据表明，根据坏血病的预防来设定人类 AA 需求，可能会导致 AA 血浆水平过低，无法预防牙龈出血倾向增加。牙龈出血倾向和视网膜出血与低 AA 血浆水平一致，因此可能反映了一种全身性微血管病理，这种病理可以通过增加每日 AA 摄入量来逆转。
