Study: L-arginine and vitamin C reduced the Long-Covid symptoms in one month

Tosato M, Calvani R, Picca A. Effects of an L-arginine-plus vitamin-C-supplementation on physical performance, endothelial function and continuing fatigue in adults with a long covid: a simply blind, randomized, controlled study. nutrients . 2022; 14 (23): 4984.

Study goal

Determination of the effects of a nutritional supplement with oral L-arginine and vitamin C on physical performance, measured by a 6-minute heme test, for subjects with long covid disease (in accordance with the criteria of the World Health Organization (WHO)). The secondary results included the assessment of muscle strength, the endothelial function and the tiredness in connection with the nutritional supplement with these two nutrients.

Key to take

An oral nutritional supplement with 3.2 g L-arginine and 1 g of liposomal vitamin C over 28 days improved physical performance, muscle strength, endothelial function and fatigue in adults with long covid.

Design

single center, simple blind, placebo-controlled, randomized clinical study

participant

The study was carried out in an outpatient clinic in Rome, Italy. The participants were adults with an earlier SARS-COV-2 infection (severe acute respiratory syndrome coronavirus 2), confirmed by PCR tests (polymerase chain reaction), a negative exploitation test for at least 4 weeks before enrolling and with long-covid symptoms (according to the WHO criteria). for long covid).

The average age of the participants was 50.5 years (20–60 years), and 65.2 % were women. The meantime of the Covid 19 diagnosis until the start of the course was 254 days. About half of the participants were hospitalized with active covid, 8.7 % were in the intensive care unit.

The researchers included 50 patients into the study and distributed them to the intervention and placebo arm in equal parts. Two participants withdrew from every arm before the intervention began. At the beginning of the course, the intervention and placebo group were similar in terms of anthropometric, clinical and functional features.

Interventions

The intervention consisted of 1.66 g L-arginine and 500 mg of liposomal vitamin C, which were taken orally twice a day (bioarginina). ^{® c, Farmaceutici Damor, Naples, Italy). The same manufacturer made the placebo. The shape of the nutritional supplement and placebo was unclear (e.g. potency, capsule, other).}

studied study parameters

In order to assess the primary result of physical resilience, the researchers measured the distance covered in a 6-minute heme test. They carried out this test at the beginning of the study and on the 28th day on a marked inner corridor.

In order to assess the secondary result of muscle strength, the researchers used a hydraulic, hand -held dynamometer to measure the capacity.

In order to assess the secondary measure of the endothelial function, they carried out a river-mediated dilation test, in which the change in the arteria brachialis dilation was essentially measured after 5 minutes of forearmishemia, which was generated by a blood pressure cuff.

The researchers measured the secondary end result of the person of exhaustion with the question: "I had the feeling that everything I did was an effort." The answer "mostly or constantly" indicated a persistent fatigue. This is point 7 of the depression scala of the Center for Epidemiological Studies 1 and serves to measure physical frailty 2 because it is more related to fatigue than with depression.

primary result

The primary result of this intervention study was to determine the effect of an oral addition of L-arginine with liposomal vitamin C on the distant distance during the 6-minute heme test as a measure of physical performance.

most important findings

This study was 80 % equipped with performance to determine a difference of at least 35 meters at the 6-minute heme test. This difference corresponds to a minimally clinically significant difference.

The effects of the intervention were measured on the 28th day. The mean serum-l arginine concentration rose in the intervention group compared to placebo (+60.2 μm vs. +11.0 μm; p = 0.02).

The primary endpoint, the middle distance at the 6-minute heme test, increased by 30 meters in the intervention group, while there was no change in the placebo group ( p = 0.001). The average difference between the groups was 50 meters (95 %AI: 20.0–80.0 m; effect size = 0.56).

There were also statistically significant differences in the secondary endpoints.

The handle force increased by 3.4 kg compared to an increase of 1.0 kg in placebo ( p = 0.03). The average difference was 3.4 kg (95 %ki: 0.5–9.4 kg; effect size = 0.37). The dilation conveyed by the river rose by 14.3 % in the intervention group compared to 9.4 % in the placebo group ( p = 0.03). The average difference was 3.4 % (95 % KI: 0.4–6.5; effect size = 0.66).

On the 28th day, 8.7 % of the intervention group reported tiredness compared to 80.1 % of the placebo group ( p≤ 0.0001). There was a high degree of correlation between the primary end point and all secondary endpoints.

Transparency

The authors received no external financing for this study and the authors did not state any conflicts of interest. The addition was donated by the manufacturer, which did not play a role in the design or interpretation of the study.

Effects and restrictions for practice

According to the Centers for Disease Control and Prevention, every fifth American adult develops Long Covid. ^{4 The consequences of a long covid disease are considerable with regard to a reduced quality of life and an increased risk of chronic diseases.}

Although the pathophysiology of long-covid is not fully clarified, there are several insights that support the hypothesis that changes in L-arginine metabolism are based on some long-covid symptoms. L-arginine is metabolized by both nitrogen oxide synthase and arginase. The metabolism of nitrogen monoxide synthase generates nitrogen monoxide (NO). No is an essential part of the endothelial function, the functional disorder of which affects the vascular tone, increases thrombosis and leads to inflammation. ^{5 If L-arginine is preferred by arginase, less is available for the formation of NO. As a result, the endothelial function, an increase in thrombosis and inflammation is impaired. Previous studies have shown that a Covid 19 infection leads to a reduced L-arginine with highly regulated arginase activity. 6.7 Based on these findings, the idea of ​​supplementing L-arginine is logical. In addition, the addition with vitamin C increases the intracellular tetrahydrobiopter, which in turn is needed by nitrogen oxide synthase to form NO. 8}

In accordance with this underlying hypothesis, this study showed that oral nutritional supplements with L-arginine and liposomal vitamin C improved the endothelial function. It is not surprising that the researchers in adults with long covid improvements in the associated clinical results of improved physical performance (6-minute walking distance), increased muscle strength and lower tiredness. It is particularly encouraging that these clinically significant results were achieved in a relatively short time, namely only one month, and with moderate cans. The researchers find that other studies showed that L-arginine supplementation improves the aerobic and anaerobic fitness, especially in untrained people. ^{9 This clearly describes the population group of people with long-covid.}

In view of the cheap security profile for both L-arginine and for vitamin C and against the background of considerable morbidity in connection with long-covid, this relatively simple supplement strategy deserves a clinical test. This study is limited by the relatively small number of participants and the fact that the study was carried out at a single center. Even if these results should be considered temporary, these results offer a clinically realizable strategy for a group of patients for whom only a few validated options exist.