Macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2: A narrative review.

BACKGROUND: COVID-19 can lead to critical illness and induce hypermetabolism, protein catabolism, and inflammation. These pathological processes may alter energy and protein requirements, and certain micronutrients may attenuate the associated detriments. This narrative review summarizes the macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2. METHODS: We searched four databases for randomized controlled trials (RCTs) and studies that measured macronutrient and micronutrient requirements, published from February 2020 to September 2022. RESULTS: Ten articles reported on energy and protein requirements, and five articles reported the therapeutic effects of ω-3 (n = 1), group B vitamins (n = 1), and vitamin C (n = 3). Patients' resting energy expenditure gradually increased with time, measuring approximately 20 kcal/kg body weight (BW), 25 kcal/kg BW, and 30 kcal/kg BW for the first, second, and third week onwards, respectively. Patients remained in negative nitrogen balances in the first week, and a protein intake of ≥1.5 g/kg BW may be necessary to achieve nitrogen equilibrium. Preliminary evidence suggests that ω-3 fatty acids may protect against renal and respiratory impairments. The therapeutic effects of group B vitamins and vitamin C cannot be ascertained, although intravenous vitamin C appears promising in reducing mortality and inflammation. CONCLUSION: There are no RCTs to guide the optimal dose of energy and protein in critically ill patients with SARS-CoV-2. Additional larger-scale, well-designed RCTs are needed to elucidate the therapeutic effects of ω-3, group B vitamins, and vitamin C.

Determination of B Vitamins by Double-Vortex-Ultrasonic Assisted Dispersive Liquid-Liquid Microextraction and Evaluation of their Possible Roles in Susceptibility to COVID-19 Infection: Hybrid Box-Behnken Design and Genetic Algorithm.

OBJECTIVES: In this study, double-vortex-ultrasonic assisted dispersive liquid-liquid microextraction (DVUDLLME) was applied to determine the concentration of vitamin B9, 5-methyl tetrahydrofolate (5-MeTHF) and vitamin B12 in human serum samples. METHODS: High-performance liquid chromatography (HPLC) coupled with DVUDLLME was applied to analyze vitamins B in patients with Coronavirus disease (COVID-19). Then, significant variables were chosen and optimized using the hybrid Box-Behnken design and genetic algorithm. RESULTS: The detection limits of DVUDLLME-HPLC were 0.21 ng mL-1, 0.18 ng mL-1 and 55 pgmL-1 for vitamin B9, 5-MeTHF and vitamin B12, respectively. Subsequently, DVUDLLME-HPLC was applied to measure B vitamins and investigated their possible roles in susceptibility to COVID-19 infection. Fifty-seven percent of the patients without an underlying disease have significantly lower serum vitamin B12 levels in comparison to controls. CONCLUSIONS: The advantages of this method are low detection limit, simple preparation, low retention time and the use of a cheaper technique instead of expensive mass detectors. The results suggest that vitamin B12 deficiency may decrease the immune system defenses against COVID-19 patients without an underlying disease and cause the disease to become severe. However, these works need a large population and further research, such as a randomized trial and a cohort study.

The effect of vitamin D and magnesium supplementation on clinical symptoms and serum inflammatory and oxidative stress markers in patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study aims to evaluate the effect of vitamin D and magnesium supplementation on clinical symptoms and serum inflammatory and oxidative stress markers in patients with COVID-19. TRIAL DESIGN: This study is a 4-arm randomized, double-blind, placebo-controlled clinical trial with a factorial design and the intervention period is 3 weeks. PARTICIPANTS: This study is conducted on COVID-19 patients admitted to the Shahid Mohammadi hospital in Bandar Abbas, Iran, who are eligible for inclusion in the study. Patients are included only if they meet all of the following criteria: (1) aged from 18 to 65 years old; (2) confirmation of COVID-19 by RT-PCR test; (3) completing informed consent; (4) passing less than 48 h since the patient's hospitalization; (5) no skin or gastrointestinal allergies due to taking multivitamin supplements, vitamin D, and magnesium; and (6) having more than 30 breaths per minute and less than 93% oxygen saturation in room air and sea level. Patients are excluded if they have any of the following conditions: (1) pregnancy or lactation; (2) taking a daily multivitamin or take a vitamin D or magnesium supplement in the last month; (3) participating in other clinical trials; (4) renal failure or dialysis, severe liver disease or cirrhosis; (5) known diagnosis of hypercalcemia; (6) discharging from the hospital less than 24 h after the start of the intervention; (7) history of kidney stones in the last year; (8) transfer the patient to the ICU; (9) baseline vitamin D levels above 80 ng/ml; (10) baseline magnesium levels above 2.6 mg/dl; and (11) unwillingness of the patient to continue the study. INTERVENTION AND COMPARATOR: Participants will be randomly allocated to one of the four following groups: (A) vitamin D (two 50,000 IU capsules at the beginning of the study, two 50,000 IU capsules on the 4th day, one 50,000 IU capsule on the 11th day, and one 50,000 IU capsule on the 17th day) and magnesium supplement (300 mg/day); (B) vitamin D capsule and magnesium placebo; (C) magnesium supplement and vitamin D placebo; and (D) vitamin D placebo and magnesium placebo. MAIN OUTCOMES: The resolution of clinical symptoms (fever, dry cough, shortness of breath, headache, myalgia, oxygen saturation, and mortality rate) and interpretation of laboratory assays (CRP, MDA, TAC, WBC, neutrophils count, lymphocytes count, ratio of neutrophils to lymphocytes, levels of 25 hydroxyvitamin D and magnesium) will be assessed in the study groups. RANDOMIZATION: A computer-generated block randomization list is used for randomization. BLINDING (MASKING): Investigators and patients are blinded to group allocation and treatment. A double-blind design is achieved using matched placebos. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 104 eligible patients are randomized into four groups of 26 subjects (1:1:1:1 allocation ratio). DISCUSSION: With the rapid prevalence of COVID-19 in recent years, more attention has been paid to effective dietary supplementation to improve clinical symptoms and biochemical parameters in these patients. To our knowledge, this is the first study to evaluate the effects of vitamin D supplementation in combination with magnesium or alone with respect to this infectious disease. The findings of the current RCT will provide evidence regarding the effectiveness of dietary supplementation strategies to improve COVID-19 outcomes. TRIAL STATUS: Ethical approval of the first version of the study protocol was obtained from the medical ethics committee of Hormozgan University of Medical Sciences, Bandar Abbas, Iran on May 30, 2021 (IR.HUMS.REC.1400.085). Currently, the recruitment phase is ongoing since August 23, 2021, and is anticipated to be complete by the end of August 2022. TRIAL REGISTRATION: The study protocol was registered in the Iranian Registry of Clinical Trials ( https://www.irct.ir ; IRCT20210702051763N1) on August 14, 2021. https://www.irct.ir/trial/57413 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Associations of depression and intake of antioxidants and vitamin B complex: Results of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Optimum functioning of the central nervous system is dependent on a wide range of nutrients, so mental illness can be impacted by diet via several mechanisms. We aimed to investigate the associations of antioxidants (vitamin A, C and E, and selenium and zinc) and vitamin B complex (B6, folate and B12) intake with depression in 14,737 subjects of the Brazilian Longitudinal Study of Adult Health. METHODS: Baseline cross-sectional data was analyzed. Micronutrients intake was measured using the Food Frequency Questionnaire, and depression was assessed using the Clinical Interview Schedule Revised. Logistic regression models were built using daily intake quintiles of micronutrients. RESULTS: A significant inverse relationship was observed between depression and higher intake of selenium, zinc, vitamins B6 and B12 for the total sample. Among women, a similar pattern of associations was observed, in addition to the higher intake of vitamins A and C. Among men, a significant inverse relationship between depression was observed only with the intake of vitamins B12 and B6. Higher total antioxidant intake was significantly associated with lower odds of depression and an inverse dose-response effect between total antioxidant intake and clinical severity of depression was observed among women, in adjusted models. LIMITATIONS: Recall bias in assessing diet. Misclassification bias regarding current depression. CONCLUSIONS: Depression is associated with lower intake of antioxidants and B vitamins. Higher intake of selected micronutrients may contribute to reduce depression occurrence and severity.

The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization.

The COVID-19 pandemic has caused a global public health emergency. Nutritional status is suggested to be related to the severity of COVID-19 infection. Herein, we aimed to explore the impact of using vitamin and mineral supplements prior to COVID-19 infection on disease severity and hospitalization. In addition, the prior use of aspirin as an anticoagulant on the disease severity was investigated. A cross-sectional, self-administered survey was conducted between March and July 2021. Recovered COVID-19 individuals (age ≥ 18 years, n = 2148) were recruited in the study. A multivariate logistic regression was used to evaluate the associations of supplements and aspirin use with COVID-19 disease severity and hospitalization status. Among the participants, 12.1% reported symptoms consistent with severe COVID-19, and 10.2% were hospitalized due to COVID-19. After adjustment for confounding variables (age, gender, BMI, cigarette smoking status, and the number of comorbidities), the multivariate logistic regression model showed that the consumption of vitamin D supplements prior to COVID-19 infection was associated with a significant decrease in disease severity (OR = 0.68, 95% CI 0.50 - 0.92; P = 0.01), and a lower risk of hospitalization (OR = 0.64, 95% CI 0.45 - 0.89; P = 0.01). On the other hand, there were no significant differences in the frequencies of severe illness and hospitalizations with the consumption of vitamin A, folic acid, vitamin B12, vitamin B complex, vitamin C, zinc, iron, selenium, calcium, magnesium, omega 3, and aspirin before COVID-19 infection. Among the investigated nutrients, the use of vitamin D prior to COVID-19 infection was associated with reduced disease severity and hospitalization. However, more studies are required to confirm this finding.

Trends of folate, vitamin B12 , and homocysteine levels in different trimesters of pregnancy and pregnancy outcomes.

OBJECTIVE: To evaluate the effect of folate and vitamin B12 levels on pregnancy progression and outcomes. METHODS: The present study is a prospective follow up study of 100 pregnant women. Biochemical investigations (plasma homocysteine, folate, and vitamin B12 levels) were performed on all pregnant women in first, second, and third trimesters. Nonparametric tests were used to compare the differences in median levels and odds ratio analysis for the assessment of the risk between the selected biomarkers and adverse pregnancy progression and outcomes. RESULTS: The pregnant women at their first antenatal care visit were found to be predominantly folate replete (97%) and vitamin B12 deficient (60%). Hyperhomocysteinemia in first and second trimesters was found to pose more than 3-fold increased risk for adverse pregnancy outcomes (P = .006 and .0002, respectively). Low birth weight (LBW) was found to be the most common adverse pregnancy outcome (52%), and was significantly associated with vitamin B12 deficiency in the first and second trimesters (82%, P < .0001; 71.4%, P = .04, respectively). CONCLUSION: The vitamin B12 deficiency is more common among Indian pregnant women as compared to folate deficiency. Hyperhomocysteinemia is an independent risk factor for pregnancy complications. Vitamin B12 deficiency in first and second trimesters is associated with LBW babies.

Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19. TRIAL DESIGN: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial. PARTICIPANTS: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month. INTERVENTION AND COMPARATOR: Duration of intervention: 7 days from randomization Intervention in the treatment group: Vitamin A 25,000 IU daily Vitamin D 600,000 IU once during study Vitamin E 300 IU twice daily Vitamin C is taken four times per day B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 µg, folic acid 400 µg, and cyanocobalamin 5 µg] The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand). MAIN OUTCOMES: 1. Weight, height, and BMI 2. Severity of pulmonary involvement according to CT scan 3. Respiratory support (invasive or non-invasive) 4. Percentage of oxygen saturation (SpO2 level) 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α 6. The patient's body temperature 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys) 8. Duration of hospitalization 9. Mortality rate RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients. BLINDING (MASKING): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The researchers plan to include 60 patients in total, with 30 patients in each group. TRIAL STATUS: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials IRCT20200319046819N1 . Registered on April 4, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).