BreatheCore

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Vitamin C

Efficacy of Vitamin C Supplementation on Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis¹

Background: In recent years, the pleiotropic roles of antioxidants have drawn extensive attention in various diseases. Vitamin C is a well-known antioxidant, and it has been used to treat patients with chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis aim to demonstrate the impact of vitamin C supplementation in patients with COPD.

Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, and China Science and Technology Journal Database (cqvip.com) for eligible randomized controlled trials (RCTs) from their respective inception to May 18th, 2021, by using the searching terms of COPD, vitamin C, and RCTs. A meta-analysis was performed to evaluate the effects of vitamin C on lung function, antioxidant levels, and nutritional conditions in COPD patients by using Review Manager (Version 5.4).

Results: Ten RCTs including 487 participants were eligible for our study. Meta-analysis results showed that vitamin C supplementation (≥400 mg/day) can significantly improve the forced expiratory volume in one second as a percentage (FEV1%) in COPD (SMD:1.08, 95% CI:0.03, 2.12, P=0.04). Moreover, vitamin C supplementation significantly improved the ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) (WMD:0.66, 95% CI: 0.26, 1.06, P=0.001), vitamin C level in serum (SMD:0.63, 95% CI: 0.02, 1.24, P=0.04) and glutathione (GSH) level in serum (SMD:2.47, 95% CI: 1.06, 3.89, P=0.0006). While no statistically significant difference was observed in body mass index (BMI), fat-free mass index (FFMI), vitamin E level and superoxide dismutase (SOD) level in serum.

Conclusion: Vitamin C supplementation could increase the levels of antioxidation in serum (vitamin C and GSH) and improve lung function (FEV1% and FEV1/FVC), especially in patients treated with vitamin C supplementation greater than 400 mg/day. However, further prospective studies are needed to explore the role of vitamin C in improving nutritional status.

Source: Lei T., Lu T., Yu H., Su X., Zhang C., Zhu L., Yang K., Liu J. Efficacy of Vitamin C Supplementation on Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis. 2022 Sep 10. PMID: 36118282, PMCID: PMC9473551, DOI: 10.2147/COPD.S368645

Improved lung function in children born to vitamin C—treated pregnant smokers²

Question: Among offspring, what is the therapeutic efficacy of vitamin C-treated pregnant smokers, compared with placebo, on airway function and wheezing?

Design: Follow-up observational study to a randomized controlled trial: Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP).

Setting: Oregon, Washington, and Indiana.

Participants: 5-year-old children born to mothers in the study (above).

Intervention: Vitamin C (500 mg/d) or placebo.

Outcomes: Offspring’s (5-year-olds) forced expiratory flow measurements.

Main Results: 192 (90.1%) had successful forced expiratory flow (FEF) measurements at age 5 years; 212 (99.5%) were included in the analysis of wheezing. Offspring of the vitamin C group compared with placebo had 17.2% significantly higher mean (SE) measurements of FEF25-75 at age 5 years, 1.45 (0.04) vs 1.24 (0.04) L/s; adjusted mean difference, 0.21 (95% CI, 0.13-0.30, P < .001). Improved FEF50, FEF75, and FEV1 were also statistically significant. These same children demonstrated decreased wheeze, 28.3% vs 47.2%; estimated odds ratio, 0.41 (95% CI, 0.23-0.74).

Conclusions: Offspring of Vitamin C–treated pregnant smokers demonstrated better lung function and decreased wheezing compared with offspring of placebo–treated pregnant smokers.

Commentary: The adverse effects of maternal prenatal cigarette smoking on infant development have been known since late in the last century. Avoiding cigarette smoke exposure (both personal and secondhand smoke) is ideal. However, for women who are pregnant and have been unable to stop smoking, vitamin C supplementation may afford protective effects on children’s lung function, as reported in this VCSIP follow-up study, a follow-up observational study of an original well-designed clinical trial. Caregiver postnatal cigarette smoking was similar in both groups. Thus, it appears that prenatal vitamin C supplementation in smokers has long-term salutary effects on lung function growth in the children. These findings are consistent with the Developmental Origins of Health and Disease paradigm, which posits that environmental influences during early development affect the risk of later pathophysiologic processes associated with disease. 1) Identifying factors that alleviate these exposures is critical. Prenatal vitamin C supplementation in smokers who are unable to quit joins the list of potential nutritional interventions, including vitamin D, 2) and fish oil, 3) that may provide resilience against environmental exposures. Future research will need to consider these interventions and uncover others that may mitigate or obviate the effects of these adverse exposures on child development.

Source: Litonjua A., MD, MPH. Improved lung function in children born to vitamin C—treated pregnant smokers. October 2023. The Journal of Pediatrics. DOI: 10.1016/j.jpeds.2023.02.032

Vitamin C Supplementation and Respiratory Infections: a Systematic Review³

Abstract

In this review, the vitamin C trials with military personnel and with other subjects living under conditions comparable to those of military recruits are analyzed to find out whether vitamin C supplementation affects respiratory infections. For this systematic review, we identified seven trials with military personnel, three trials with students in crowded lodgings, and two trials with marathon runners. Eight of these trials were double blind and placebo controlled and seven were randomized. Five small trials found a statistically significant 45 to 91% reduction in common cold incidence in the vitamin C group. These trials were short and the participants were under heavy exertion during the trial. Furthermore, three other trials found a statistically significant 80 to 100% reduction in the incidence of pneumonia in the vitamin C group. The large number of positive findings seems to warrant further consideration of the role of vitamin C in respiratory infections, particularly in military recruits.

Source: Hemilä H., MD, PhD. Vitamin C Supplementation and Respiratory Infections: a Systematic Review. Military Medicine, Volume 169, Issue 11, November 2004, Pages 920–925, DOI: 10.7205/MILMED.169.11.920

Vitamin C, E

Effect of vitamin supplementation on lung injury and running performance in a hot, humid, and ozone-polluted environment⁴

Abstract

In this study, the effect of vitamin C and E supplementation on lung injury and performance of runners were analyzed. Using a randomized, double-blinded, crossover design, nine runners participated in two experimental trials: a 2-week Vitamin trial (vitamin C = 500 mg/day + vitamin E = 100 IU/day) and a 2-week Placebo trial. At the end of each supplementation period the runners performed an 8-km time-trial run in a hot (31°C), humid (70% rh), and ozone-polluted (0.10 ppm O3) environmental chamber. Nasal lavage and blood samples were collected pre-, post-, and 6-h post-exercise to assess antioxidant status and CC16 as lung injury marker. Higher plasma (pre- and post-exercise) and nasal lavage (post-exercise) antioxidant concentration were found for the Vitamin trial. Nevertheless, this did not result in performance differences (Vitamin trial: 31:05 min; Placebo trial: 31:54 min; P = 0.075) even though significant positive correlations were found between antioxidant concentration and improvement in time to complete the run. CC16 was higher post-exercise in the Placebo trial (P < 0.01) in both plasma and nasal lavage. These findings suggest that antioxidant supplementation might help to decrease the lung injury response of runners when exercising in adverse conditions, but has little effect on performance.

Source: Gomes E., Allgrove J., Florida-James G., Stone V. Effect of vitamin supplementation on lung injury and running performance in a hot, humid, and ozone-polluted environment.  Edinburgh Napier University. 18 August 2011. DOI: 10.1111/j.1600-0838.2011.01366.x

Vitamin C, E, D

Nutrition as a modifiable factor in the onset and progression of pulmonary function impairment in COPD: a systematic review⁵

Context: Chronic obstructive lung disease (COPD) is a progressive lung disease characterized by persistent airflow limitation. An increasing amount of evidence suggests an effect of dietary quality on the risk of COPD in the general population and pulmonary function decline in patients with COPD.

Objective: The association of dietary intake and nutrient status with COPD risk and onset, as well as pulmonary function decline (change in forced expiratory volume in 1 second, forced vital capacity, or the ratio of the former to the latter) in patients with COPD was investigated in this systematic review.

Data sources: The PubMed database was searched by combining terms of pulmonary function or COPD with diet, nutrient status, or nutritional supplementation.

Data extraction: Original studies and systematic reviews and meta-analyses were included. Articles obtained were independently screened for relevance on the bases of title and abstract by 2 researchers. Eventually, 89 articles were included in the analysis.

Results: The unhealthy Western-style diet is associated with an increased risk of COPD and an accelerated decline of pulmonary function. Intake of fruit, vegetables, dietary fibers, vitamins C and E, polyphenols, and β-carotene were individually associated with lower COPD risk, whereas consumption of processed meat was associated with higher COPD risk. Data on the effect of dietary quality on pulmonary function decline in patients with COPD are limited and inconsistent. Strong evidence for beneficial effects on pulmonary function decline was found only for vitamin D supplementation.

Conclusion: Considering the increasing burden of COPD, more attention should be given to dietary quality as a modifiable factor in disease development and progression in patients with COPD.

Source: Iersel L.E.J., Beijers R.J.H.C.G., Gosker H.R., Schols A.M.W.J. Nutrition as a modifiable factor in the onset and progression of pulmonary function impairment in COPD: a systematic review.  2022 May 9. PMID: 34537848, PMCID: PMC9086787, DOI: 10.1093/nutrit/nuab077

Ginseng

Prevention and Control of Acute Respiratory Viral Infections in Adult Population: A Systematic Review and Meta-Analysis on Ginseng-Based Clinical Trials⁶

Introduction: Acute respiratory infections are continuously emerging. Discovered in Wuhan city, China in 2019, COV-SARS-2 and most viral respiratory diseases presently do not have a definitive cure. This paper aims to evaluate the therapeutic effectiveness of ginseng for prevention and control of acute respiratory illness including SARS-COV-2 in adult population.

Method: We performed a systematic literature review using databases PubMed, Medline, Scopus, Google Scholar, Web of Science, and Cochrane library from 1st through the 27th of April 2020. All related articles that reported the use of Ginseng in COVID-19 patients were included in this analysis. Screening was done by 2-independent researchers. The meta-analysis was performed using comprehensive meta-analysis package.

Result: 596 articles were retrieved for the time frame. After screening, 5 articles with RCTs outcomes relevant to the review were selected. Ginseng was found to be effective in the reduction of risk by 38 % and 3-days shorter duration of acute respiratory illness (ARI) in all trials than placebo.

Conclusion: As the world continues to race to find a cure, it is important to consider the use of ginseng which has been proven over the years to be effective in the treatment of acute respiratory illnesses. Further studies should however be conducted to determine the right dosage to improve efficacy and prevent adverse events.

Source: Adusei-Mensah F., Agjei R.O., Awoniyi L.O., David L.K., Awoniyi F.B., Adeyemi O.S., Olawuni A., Adegbite A. Prevention and Control of Acute Respiratory Viral Infections in Adult Population: A Systematic Review and Meta-Analysis on Ginseng-Based Clinical Trials. July 25, 2021. DOI: 10.1101/2021.07.23.21260970

Oral ginseng formulae for stable chronic obstructive pulmonary disease: a systematic review⁷

Abstract

Ginseng alone or combined with other herbs has been increasingly used for chronic obstructive pulmonary disease (COPD). This review aims to evaluate the effectiveness and safety of oral Ginseng formulae for stable COPD. Four English databases and three Chinese databases were searched to identify randomized controlled trials. Methodological quality was assessed by Cochrane risk of bias and Jadad's scale. Data were analyzed using Review Manager 5.0. Twelve studies overall of low quality, involving 1560 participants were included. Results of three studies showed a mean difference (MD) of 0.30 (95%CI 0.02 to 0.58) for forced expiratory volume in 1 s (FEV(1)) improvement of Ginseng formulae versus placebo control. Findings of three studies revealed an MD of 9.43 (95%CI 3.64 to 15.21) of FEV(1) % predicted between Ginseng formulae and placebo control. Quality of life (Qol) measured by St. George's Respiratory Questionnaire was improved (MD -10.32, 95%CI -14.99 to -5.65) with Ginseng formulae plus pharmacotherapy versus pharmacotherapy alone in one study. There were no severe adverse events reported. Ginseng formulae for stable COPD patients show promising evidence of lung functions and Qol improvement. However, the degree of benefit is uncertain due to potential risk of bias of the included studies.

Source: An X., Zhang A.L., Yang A.W., Lin L., Wu D., Guo X., Shergis J.L., Thien F.C.K., Worsnop C.J., Xue C.C. Oral ginseng formulae for stable chronic obstructive pulmonary disease: a systematic review. 2011 Feb. PMID: 21146973, DOI: 10.1016/j.rmed.2010.11.007

St. John’s Wort

Role of Herbal Medication in Tobacco Cessation Treatment: A Systematic Review and Meta-analysis⁸

Background: Literature reports randomized trials have examined herbal drugs and other smoking cessation therapies such as aromatherapy acupuncture but no comprehensive overview of the overall results has been provided. The present systematic review and meta-analysis aimed to describe the overall effectiveness and safety of herbal medicines.

Methods: This study was conducted from December 2020 to April 2021 by searching seven databases. Herbal drugs have been shown to help people quit smoking in randomized controlled studies. Two teams of researchers independently extracted the data.

Findings: A total of 12 trials with 762 smokers were included in this study. The heterogeneity I2 was 43.6% with P=0.03 (Cochrane Q test) and χ2=15.77. The overall odds ratio (OR) at 95% confidence interval (CI) was 0.91 (0.68- 1.20) which shows a protective factor of herbal preparations and very low heterogeneity. The herbal treatments such as Vernonia cinerea, St. John's Wort, and lavender essential oil were significantly related to a higher continuous abstinence rate (CAR) compared to the controls with risk ratio (RR): 2.13 (0.57-4.61) at week 8; RR: 2.72 (0.77-5.3) at week 12; and RR: 2.77 (0.37-1.13) at week 24. A 7-day point abstinence rate (PAR) at week 8 was RR: 1.24 (0.81-6.34) with 95% CI; RR: 2.09 (0.93-8.29) at week 12, and RR: 2.11 (0.3-3.08) at week 24. Black pepper and lime were better in craving reduction than the placebo group. This study found no significant difference between the treatment and control groups in adverse effects, despite some minor side effects with herbal drugs.

Conclusion: The results of this study showed herbal treatments have the potential to help smokers quit the habit. Further well-designed trials comparing standardized herbal medicines with conventional therapy and placebo are recommended to reinforce this data.

Source: Mitra R., Rai A., Kumar A., Mitra J.K. Role of Herbal Medication in Tobacco Cessation Treatment: A Systematic Review and Meta-analysis. 2023 Jan. PMID: 37560083, PMCID: PMC10408736, DOI: 10.34172/ahj.2023.1290

Ginkgo biloba

Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia⁹

Specific aim: Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia.

Methods: Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated.

Results: There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (p<0.05).

Conclusion: Ginkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia.

Source: Xu L., Hu Z., Shen J., McQuillan P.M. Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia. 2015 Apr. PMID: 25847559, DOI: 10.1016/j.ctim.2014.12.009

Effects of Six-Week Ginkgo biloba Supplementation on Aerobic Performance, Blood Pro/Antioxidant Balance, and Serum Brain-Derived Neurotrophic Factor in Physically Active Men¹⁰

Abstract

Extracts of Ginkgo biloba leaves, a natural source of flavonoids and polyphenolic compounds, are commonly used as therapeutic agents for the improvement of both cognitive and physiological performance. The present study was aimed to test the effects of a six-week supplementation with 160 mg/day of a standardized extract of Ginkgo biloba or a matching placebo on aerobic performance, blood antioxidant capacity, and brain-derived neurotrophic factor (BDNF) level in healthy, physically active young men, randomly allocated to two groups (n = 9 each). At baseline, as well as on the day following the treatment, the participants performed an incremental cycling test for the assessment of maximal oxygen uptake. Venous blood samples taken at rest, then immediately post-test and following 1 h of recovery, were analyzed for activities of antioxidant enzymes and plasma concentrations of non-enzymatic antioxidants, total phenolics, uric acid, lipid peroxidation products, ferric reducing ability of plasma (FRAP), and serum brain-derived neurotrophic factor (BDNF). Our results show that six weeks' supplementation with Ginkgo biloba extract in physically active young men may provide some marginal improvements in their endurance performance expressed as VO₂max and blood antioxidant capacity, as evidenced by specific biomarkers, and elicit somewhat better neuroprotection through increased exercise-induced production of BDNF.

Source: Sadowska-Krępa E., Kłapcińska B., Pokora I., Domaszewski P., Kempa K., Podgórski T. Effects of Six-Week Ginkgo biloba Supplementation on Aerobic Performance, Blood Pro/Antioxidant Balance, and Serum Brain-Derived Neurotrophic Factor in Physically Active Men. 2017 Jul 26. PMID: 28933745, PMCID: PMC5579597, DOI: 10.3390/nu9080803

Ginger

Efficacy of Ginger in Patients Uncontrolled on Standard Moderate Asthma Treatment¹¹

Background and purpose: The goal of asthma therapy is to achieve clinical control and near normal lung functions. Many patients with moderate persistent asthma fail to achieve this goal with a low dose of inhaled corticosteroid (ICS) plus long-acting β2 agonist (LABA). In the present study, we have checked whether another controller medication (in the form of ginger capsule) add on to ICSlow dose + LABA helps in achieving the asthma goal or not.

Materials and methods: Thirty two adult asthmatics (17 male and 15 female) completed a 10 week trial consisting of a 1 week single blind run in period, during which placebo (250 mg capsule of lactose 3 times a day) was added to usual treatment (inhaled beclomethasone diproprionate 200 µg/twice daily plus salmeterol 50 µg/twice daily), a 4 week double blind active treatment period in which subjects received ginger (250 mg capsule of powdered ginger 3 times a day) or placebo capsule, a single blind 1 week washout period receiving placebo and a final 4 week double blind cross-over active treatment period. The primary efficacy variable was the forced expiratory volume at 1 second (FEV1); secondary efficacy variables were the peak expiratory flow (PEF) and the asthma control test (ACT) scores. These variables were measured at the completion of each phase, i.e. the end of weeks 1, 5, 6 and 10. Statistical comparisons of all variables were made by two-way analysis of variance (ANOVA) with patient, period, and treatment as fixed factors. P 0.05).

Conclusion: Powdered ginger rhizome capsule as an add on to inhaled corticosteroid and long- acting β2 agonist is effective in the improvement of FEV1, PEF, and ACT scores of the patients of a moderate type of persistent asthma uncontrolled on standard treatment.

Source: Davood F., Ali S., Nazanin M.S., Masud A., Siavash A. Efficacy of Ginger in Patients Uncontrolled on Standard Moderate Asthma Treatment. 15 March 2012. Journal of Mazandaran University of Medical Sciences.

Effect of enteral feeding with ginger extract in acute respiratory distress syndrome¹²

Purpose: The purpose of this study is to evaluate the effects of an enteral diet enriched with ginger extract on inflammatory factors, respiratory profile, and outcome of patients with acute respiratory distress syndrome (ARDS).

Materials and methods: Thirty-two patients with ARDS were randomized to receive a high-protein enteral diet enriched with ginger or placebo. Serum levels of interleukin (IL) 1, IL-6, tumor necrosis factor α, and leukotriene B4; red blood cell glutathione; oxygenation; and static compliance were measured on days 0, 5, and 10.

Results: Patients fed enteral diet enriched with ginger had significantly lower serum levels of IL-1, IL-6, and tumor necrosis factor α and higher level of RBC glutathione on days 5 and 10 compared with control group (P < .05). Significant improvement in oxygenation was observed on day 5 (P = .02) and 10 (P = .003) in ginger group compared with control group. Static compliance was increased on day 5 (P = .01) in ginger group compared with control group. A significant difference was found in duration of mechanical ventilation (P = .02) and length of intensive care unit stay (P = .04) in favor of ginger group. We did not find any difference in barotraumas, organ failure, and mortality between the study groups.

Conclusions: An enteral diet supplemented with ginger in patients with ARDS may be beneficial for gas exchange and could decrease duration of mechanical ventilation and length of stay in intensive care unit.

Source: Shariatpanahi Z.V., Mokhtari M., Taleban F.A., Alavi F., Surmaghi M.H.S., Mehrabi Y., Shahbazi S. Effect of enteral feeding with ginger extract in acute respiratory distress syndrome. 2013 April. PMID: 22884532, DOI: 10.1016/j.jcrc.2012.04.017

References:

1. https://pubmed.ncbi.nlm.nih.gov/36118282/
2. https://www.jpeds.com/article/S0022-3476(23)00186-5/fulltext
3. https://academic.oup.com/milmed/article-abstract/169/11/920/4283642?redirectedFrom=fulltext#google_vignette
4. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0838.2011.01366.x
5. https://pubmed.ncbi.nlm.nih.gov/34537848/
6. https://www.medrxiv.org/content/10.1101/2021.07.23.21260970v1.article-info
7. https://pubmed.ncbi.nlm.nih.gov/21146973/
8. https://pubmed.ncbi.nlm.nih.gov/37560083/
9. https://pubmed.ncbi.nlm.nih.gov/25847559/
10. https://pubmed.ncbi.nlm.nih.gov/28933745/
11. https://www.semanticscholar.org/paper/Efficacy-of-Ginger-in-Patients-Uncontrolled-on-Davood-Ali/72cbfdc65ad4ca281e67c71e86f0e0ea5abb2a31
12. https://pubmed.ncbi.nlm.nih.gov/22884532/