Main Research Findings

1) Supplementation with vitamin A reduces rates of morbidity and mortality in children with severe measles.

2) Daily administration of vitamin A resulted in positive clinical and endoscopic effects, as well as a decrease in disease index in patients with ulcerative colitis.

 

Selected Data

1) The study conducted by the research team of Hussey et al evaluated the effect of oral vitamin A on morbidity and mortality in children hospitalized with acute measles. The study followed a randomized, double-blind, placebo-controlled design. Ethical approval for the trial was granted by the Medical Faculty’s ethics and research committee, and the study was capped at a maximum enrollment of 200 children due to predefined criteria, including a fixed end date.

Children under the age of 13 who were admitted to the hospital for measles-related complications were considered eligible for inclusion in the study. However, several exclusion criteria were applied. Children were excluded if they had received vitamin A treatment before hospital admission, exhibited signs of xerophthalmia, a condition caused by vitamin A deficiency, either at the time of admission or during the hospital stay, had a measles rash for more than four days, or if their parents did not consent to participation [1].

Eligible children were randomly assigned to one of two groups: one received oral vitamin A and the other a placebo. The vitamin A group was given a total dose of 400,000 IU of water-miscible vitamin A in the form of retinyl palmitate administered in two equal doses. The first dose was given at the time of admission and the second on the following day. These were delivered either orally or via a nasogastric tube, depending on the child’s condition. The syringes used for administration were coded according to a random-number table to maintain the double-blind aspect of the study. Only after the study was completed were the treatment codes revealed. Routine care continued under regular ward staff, including the administration of oxygen, intravenous fluids, and antibiotics where appropriate. No additional vitamin supplements were given [1].

One of the study investigators conducted daily assessments of the participants. Initial evaluations included recording each child’s weight and height, drawing venous blood samples, and performing relevant lab tests. Anthropometric data were compared against standards set by the U.S. National Center for Health Statistics, while blood tests measured hemoglobin levels, white cell counts, and differential counts. In addition, serum samples were collected and stored at -70°C for further analysis. Total serum protein and albumin were measured through automated biochemical analysis. Serum levels of vitamin A were measured using high-performance liquid chromatography, and vitamin E levels were also incidentally recorded. A programmable integrator was used to quantify these chromatographic results. Retinol-binding protein levels were determined using radial immunodiffusion with a commercially available kit. Chest X-rays and other diagnostic investigations were performed as needed based on the child’s clinical presentation [1].

The primary outcomes of the study were evaluated using clinical criteria alone, without reliance on laboratory or imaging results unless indicated. The main outcome measures included death and severity of illness. Severity was assessed using several indicators: the length of hospital stay, the duration of pneumonia or diarrhea, the occurrence of post-measles complications such as croup or herpes stomatitis, and whether the child required transfer to a higher-level care facility for intensive treatment.

Specific clinical definitions were established for consistent assessment. Pneumonia was defined as a respiratory rate exceeding 40 breaths per minute accompanied by signs such as chest retractions, crackles, or wheezing. Diarrhea was defined as the passage of at least four liquid stools in one day. Measles-associated croup was diagnosed if it presented on the day of admission or the following day, whereas any occurrence of croup afterward was considered post-measles croup [1].

2) The research team of Masnadi et al conducted a double-blind, randomized controlled clinical trial designed to evaluate the therapeutic effects of vitamin A supplementation in patients with moderate ulcerative colitis. A total of 150 symptomatic patients aged 20 to 45 years, with Mayo scores ranging from 6 to 12, were selected to participate. These individuals had persistent symptoms despite being treated with both oral and topical 5-aminosalicylic acid, which is the standard therapy for ulcerative colitis.

Participants were excluded from the study if they were pregnant or planning pregnancy, breastfeeding, had other autoimmune or chronic infectious diseases, were regular users of vitamin A supplements, or were smokers. This ensured that the study population was relatively homogenous and free from confounding variables that could interfere with the outcomes of vitamin A supplementation [2].
Participants were randomly assigned into two groups: an intervention group and a placebo group. Randomization was carried out using computer-generated charts to minimize selection bias. Both patients and investigators were blinded to the treatment allocations, preserving the integrity of the double-blind design. The calculated sample size was based on detecting a 30% expected decrease in Mayo score. This calculation resulted in 70 subjects per group being necessary, but 75 were enrolled in each group to account for potential dropouts or protocol deviations [2].

The trial used a two-arm, parallel-group design. In both arms, the conventional treatment with 5-aminosalicylic acid remained stable for at least one month before the study began and continued throughout the trial duration. This helped isolate the effects of vitamin A as the independent variable. The intervention group received 25,000 IU of vitamin A daily in the form of retinyl palmitate, while the placebo group received identical-appearing soft gels containing no active vitamin. The supplementation period lasted for two months. Baseline anthropometric measurements were collected for all participants. Weight was measured to the nearest 0.1 kilogram, and height to the nearest 0.1 centimeter. From these measurements, body mass index was calculated using the standard formula.

The primary tool for assessing disease activity and treatment efficacy was the Mayo Clinic Score. This score is widely recognized for evaluating the severity and progression of ulcerative colitis. It includes four components: stool frequency, rectal bleeding, mucosal appearance based on endoscopic findings, and the physician’s global assessment of disease activity. For rectal bleeding and stool frequency, the worst score over the three days prior to each study visit was used to ensure accurate representation of the patient’s condition. The physician’s assessment included the patient’s own records of abdominal discomfort, general well-being, and physical examination findings, as well as performance status [2].

Mucosal inflammation, an important marker of disease activity, was assessed by an experienced gastroenterologist-endoscopist who specialized in inflammatory bowel disease. Each of the four Mayo score components was rated from 0 to 3, and the total score ranged from 0 to 12. A higher score indicated more severe disease.

Patient compliance with the treatment regimen was monitored by counting the number of unused soft gels. If patients consumed less than 80% of their prescribed capsules or altered their conventional medications during the trial, they were excluded from the final analysis to maintain study validity. The primary measure of treatment efficacy was the clinical response rate. A clinical response was defined as a decrease in the total Mayo score by at least three points or 30%, in addition to a decrease in the rectal bleeding subscore by at least one point or a final subscore of one or less. This definition ensured that both general symptom relief and specific improvements in bleeding were captured as meaningful outcomes [2].

Secondary efficacy outcomes included the proportion of patients achieving mucosal healing. Mucosal healing was defined as an endoscopic subscore of less than one, indicating minimal or no visible inflammation. This endpoint is important because it reflects not just symptomatic improvement but also resolution of the underlying disease process. The researchers also calculated the number needed to treat for both clinical response and mucosal healing. The number needed to treat provides a practical measure of treatment benefit, indicating how many patients would need to receive the intervention for one patient to benefit meaningfully [2].

 

Discussion

1) The clinical trial conducted by Hassey et al assessed the effect of high-dose oral vitamin A on children hospitalized with measles. The results reported that out of 224 children under 13 years of age admitted with measles during the study period, 35 were excluded based on preset criteria. Twelve had experienced the rash for five or more days, two had already received vitamin A treatment, eighteen were unaccompanied by a parent and consent could not be obtained, and three had parents who declined consent. This left a total of 189 children eligible and enrolled in the study. Importantly, no children were excluded for having xerophthalmia, and none withdrew from the study after entry [1].

The baseline characteristics of the two study groups, those who received vitamin A and those who received a placebo, were largely similar, although there were minor differences. Children in the vitamin A group had been admitted slightly earlier relative to the onset of their rash and had lower serum protein and albumin levels at baseline. Two-thirds of the study population were infants 12 months old or younger, with the median age being 10 months and boys making up 58% of the group.

Nutritional data revealed a high prevalence of malnutrition indicators among the participants. While 29% of the children had height-for-age measurements below the fifth percentile, weight-for-age and weight-for-height metrics were more frequently below the fifth percentile, at 50% and 39% respectively. This likely reflected recent weight loss due to measles rather than chronic malnutrition, which is relatively uncommon in the area. The most common reason for hospitalization was the combination of pneumonia and diarrhea in 64% of patients. Other primary diagnoses included diarrhea alone in 16% of patients, pneumonia alone in 13% of patients, and measles-associated croup in 7% of patients [1].

Laboratory evaluations showed widespread nutritional deficiencies, particularly in serum protein markers and vitamin A levels. The average serum concentrations for total protein, albumin, and retinol-binding protein were low. Most notably, serum retinol levels were significantly below the normal range in the majority of patients. Specifically, 92% of the children had serum retinol levels below 0.7 μmol/L, and 46% had levels below 0.35 μmol/L, putting them at high risk for xerophthalmia, though none of the children actually developed this condition during the study.

The outcome of the study strongly favored the use of vitamin A. In terms of morbidity, vitamin A significantly reduced the duration of key measles complications. Pneumonia lasted nearly twice as long in the placebo group compared to the vitamin A group, and chronic pneumonia cases were 66% more prevalent in the placebo group. Similarly, diarrhea was more prolonged in the placebo group, and the majority of chronic diarrhea cases (72%) also occurred in that group. Complications such as post-measles croup and herpes stomatitis were also more common in the placebo group, though the association with herpes stomatitis approached but did not reach statistical significance [1].

Children who received vitamin A also had a ⅓ less shorter hospital stay than those in the placebo group. In total, 77 children experienced at least one adverse outcome, with 52 of these occurring in the placebo group. The relative risk of experiencing an adverse outcome was approximately half in the vitamin A group compared to the placebo group. Additionally, younger children, under 2 years of age, were more vulnerable; only two children aged 2 years or older experienced adverse outcomes, highlighting age as a significant risk factor [1].

Finally, none of the children with normal serum retinol levels of ≥0.7 μmol/L died during the study, although this group was very small, making it difficult to draw firm conclusions. Nevertheless, the data strongly suggest that high-dose vitamin A supplementation significantly reduces both mortality and the severity of illness in children hospitalized with measles, particularly among those who are young and nutritionally compromised [1].

2) The research team of Masnadi et al presents the findings and conclusions of a randomized controlled clinical trial investigating the effects of vitamin A supplementation on patients with ulcerative colitis. Out of the original 150 participants, seven patients were withdrawn from the study: three from the vitamin A group and four from the placebo group. Consequently, data from 143 patients were included in the final analysis, with 72 in the vitamin A supplementation group and 71 in the placebo group.

Gastrointestinal side effects were relatively mild and more commonly reported in the vitamin A group. Ten participants in this group experienced nausea or a sense of abdominal fullness, compared to only three in the placebo group. These side effects were not severe enough in most cases to necessitate withdrawal from the study but are important to note when considering the tolerability of the intervention [2].

The mean age of the study participants was approximately 39.5 years, with a standard deviation of 12.7 years. The average body mass index was 26.8 kg/m², indicating that the population was generally overweight. At baseline, a statistically significant difference in anthropometric characteristics between the two groups was observed. Specifically, there was a higher prevalence of overweight and obese individuals in the intervention group compared to the placebo group. However, no significant differences were found between the groups in terms of age, duration of disease, serum vitamin A levels, or overall disease activity, suggesting that the groups were otherwise comparable at the start of the trial [2].

Following the intervention period, the vitamin A group exhibited significant improvements in several clinical parameters. There was a statistically significant decrease in the total Mayo score and its subscores, indicating reduced disease activity. Additionally, serum vitamin A levels increased significantly in this group, confirming the effectiveness of the supplementation. In contrast, the placebo group showed a significant decline in serum vitamin A levels, and there were no meaningful changes in their Mayo scores or subscores.

A one-way analysis of covariance was conducted to account for potential confounding factors, including age, sex, disease duration, BMI, and baseline values. After adjusting for these variables, significant differences between the two groups persisted in terms of serum vitamin A levels, total Mayo score, and its individual components. This further reinforces the effectiveness of vitamin A supplementation in improving clinical outcomes in ulcerative colitis patients [2].

In the vitamin A group, there was a noticeable shift toward milder disease. Specifically, the percentage of participants with mild or moderate inflammation increased, while the proportion of those with severe inflammation decreased. By the end of the study, 25% of the participants in the intervention group had achieved mild disease severity. Conversely, only 1.4% of participants in the placebo group experienced similar improvement, highlighting the superior anti-inflammatory effect of vitamin A.

In the vitamin A group, 34% of participants showed a clinical response, defined as a significant reduction in disease activity, while no clinical response was observed in the placebo group. Additionally, mucosal healing measured by endoscopic evaluation was achieved in 30.6% of the vitamin A group compared to only 8.5% in the placebo group. These differences were statistically significant demonstrating the clinical benefit of vitamin A supplementation in promoting mucosal repair and reducing inflammation [2].

The study also calculated the number needed to treat, which represents how many patients would need to be treated for one to benefit. For clinical response, the number needed to treat was three, meaning that treating three patients with vitamin A would result in one additional patient experiencing clinical improvement. For mucosal healing, the number needed to treat was five, suggesting that five patients would need to be treated for one to achieve healing of the intestinal lining. These values reflect strong therapeutic potential, especially for an accessible and affordable intervention like vitamin A [2].

In conclusion, this study provides evidence that daily supplementation with 25,000 IU of vitamin A for two months can lead to significant improvements in both clinical symptoms and mucosal healing in patients with ulcerative colitis. The intervention was generally well tolerated, with manageable side effects. Based on the number needed to treat values, the treatment appears effective, particularly for clinical response [2].

 

Disclaimer

**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).



Citations

[1] Hussey GD, Klein M. A randomized, controlled trial of vitamin A in children with severe measles. N Engl J Med. 1990;323(3):160-164. doi:10.1056/NEJM199007193230304

[2] Masnadi Shirazi K, Nikniaz Z, Masnadi Shirazi A, Rohani M. Vitamin A supplementation decreases disease activity index in patients with ulcerative colitis: A randomized controlled clinical trial. Complement Ther Med. 2018;41:215-219. doi:10.1016/j.ctim.2018.09.026

 

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