Clinical Quickies (Jan-Feb 2023)

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  1. Ingesting Whey Protein after Overnight Fast May Significantly Lower Systolic BP in Some Older Men, Potentially Causing Hypotension
  2. Strict Salt Restriction Is Associated with Worse Outcome in Younger Non-White Patients with HFpEF
  3. L-Carnitine Supplementation Does Not Increase Carotid Total Plaque Volume, but Increases Carotid Atherosclerotic Stenosis in People with Metabolic Syndrome
  4. Daily Supplementation of Vit D Improves Heart Failure Symptoms in Patients with Low Serum Vit D Status
  5. High-Dose Vit D Supplementation Potentially Prolongs the Honeymoon Phase in Kids with New-Onset Type 1 Diabetes
  6. Ashwagandha Extract Improves General Well-Being and Sexual Performance in Adult Males
  7. Berberine and Fenugreek Combo Improves Metabolic Parameters in Type 2 Diabetes Patients
  8. Vitamin B12 Ointment May Improves Radiodermatitis
  9. Six-Month Krill Oil Supplementation Improves Pain, Stiffness and Function in Patients with Osteoarthritis
  10. Hydrogen Inhalation and Hydrogen Water May Reduce Breath Alcohol Concentration and Hangover Symptoms
  11. Vitamin C Supplementation for Pregnant Smokers May Minimize the Negative Impacts of Smoking on Offspring’s Respiratory Health

1. Ingesting Whey Protein after Overnight Fast May Significantly Lower Systolic BP in Some Older Men, Potentially Causing Hypotension

ABSTRACT: Postprandial hypotension (PPH) occurs frequently in older people 65 years old. Protein-rich supplements, particularly whey protein (WP), are increasingly used by older people for various health benefits. We have reported that 70 g WP drinks cause significant, and in some cases marked, falls in blood pressure (BP) in older men. The effects of lower, more widely used, doses (~30 g) on systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) are not known. In a randomized order, eight older men (age: 72 ± 1 years; body mass index (BMI): 25 ± 1 kg/m2) after overnight fast ingested a drink containing (i) a non-caloric control (~2 kcal), (ii) 30 g of whey protein (120 kcal; ‘WP30’), or (iii) 70 g of whey protein (280 kcal; ‘WP70’).

The BP and HR were measured in this pilot study with an automated device before and at 3-min intervals for 180 min following drink ingestion. Drink condition effects were determined by repeated-measures ANOVA. The SBP decreased after both WP drinks compared to the control (p = 0.016), particularly between 120 and 180 min, with no difference in the effects of WP30 and WP70. The SBP decreased by ≥20 mmHg in more than 50% of people after both WP drinks (WP30: 63%; WP70: 75%) compared to 38% after the control.

The maximum fall in the SBP occurred during the third hour, with the nadir occurring latest after WP70. The DBP decreased non-significantly by several mmHg more after the WP drinks than after the control. The maximum HR increases occurred during the third hour, with the greatest increase after WP70. The SBP decreased after both WP drinks compared to the control, with the effects most evident between 120 and 180 min. Accordingly, ingestion of even relatively modest protein loads in older men has the potential to cause PPH.

Oberoi A, et al. Blood Pressure and Heart Rate Responses following Dietary Protein Intake in Older Men. Nutrients. 2022 May 3;14(9):1913. doi: 10.3390/nu14091913.

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2. Strict Salt Restriction Is Associated with Worse Outcome in Younger Non-White Patients with HFpEF

BACKGROUND: The optimal salt restriction in patients with heart failure (HF), especially patients with heart failure with preserved ejection fraction (HFpEF), remains controversial.

OBJECTIVE: To investigate the associations of cooking salt restriction with risks of clinical outcomes in patients with HFpEF.

METHODS: Cox proportional hazards model and subdistribution hazards model were used in this secondary analysis in 1713 participants with HFpEF from the Americas in the TOPCAT trial. Cooking salt score was the sum of self-reported salt added during homemade food preparation. The primary endpoint was a composite of cardiovascular death, HF hospitalization and aborted cardiac arrest, and secondary outcomes were all-cause death, cardiovascular death and HF hospitalization.

RESULTS: Compared with patients with cooking salt score 0, patients with cooking salt score >0 had significantly lower risks of the primary endpoint (HR=0.760, 95% CI 0.638 to 0.906, p=0.002) and HF hospitalization (HR=0.737, 95% CI 0.603 to 0.900, p=0.003), but not all-cause (HR=0.838, 95% CI 0.684 to 1.027, p=0.088) or cardiovascular death (HR=0.782, 95% CI 0.598 to 1.020, p=0.071). Sensitivity analyses using propensity score matching baseline characteristics and in patients who prepared meals mostly at home yielded similar results. Subgroup analysis suggested that the association between overstrict salt restriction and poor outcomes was more predominant in patients aged ≤70 years and of non-white race.

CONCLUSION: Overstrict cooking salt intake restriction was associated with worse prognosis in patients with HFpEF, and the association seemed to be more predominant in younger and non-white patients. Clinicians should be prudent when giving salt restriction advice to patients with HFpEF.

Li JY, et al. Salt restriction and risk of adverse outcomes in heart failure with preserved ejection fraction. Heart. 2022 Aug 11;108(17):1377-1382. doi: 10.1136/heartjnl-2022-321167.

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3. L-Carnitine Supplementation Does Not Increase Carotid Total Plaque Volume, but Increases Carotid Atherosclerotic Stenosis in People with Metabolic Syndrome

BACKGROUND: L-carnitine (L-C), a ubiquitous nutritional supplement, has been investigated as a potential therapy for cardiovascular disease, but its effects on human atherosclerosis are unknown. Clinical studies suggest improvement of some cardiovascular risk factors, whereas others show increased plasma levels of pro-atherogenic trimethylamine N-oxide. The primary aim was to determine whether L-C therapy led to progression or regression of carotid total plaque volume (TPV) in participants with metabolic syndrome (MetS).

METHODS: This was a phase 2, prospective, double blinded, randomized, placebo-controlled, two-center trial. MetS was defined as ≥ 3/5 cardiac risk factors: elevated waist circumference; elevated triglycerides; reduced HDL-cholesterol; elevated blood pressure; elevated glucose or HbA1c; or on treatment. Participants with a baseline TPV ≥ 50 mm3 were randomized to placebo or 2 g L-C daily for 6 months.

RESULTS: The primary outcome was the percent change in TPV over 6 months. In 157 participants (L-C N = 76, placebo N = 81), no difference in TPV change between arms was found. The L-C group had a greater increase in carotid atherosclerotic stenosis of 9.3% (p = 0.02) than the placebo group. There was a greater increase in total cholesterol and LDL-C levels in the L-C arm.

CONCLUSIONS: Though total carotid plaque volume did not change in MetS participants taking L-C over 6-months, there was a concerning progression of carotid plaque stenosis. The potential harm of L-C in MetS and its association with pro-atherogenic metabolites raises concerns for its further use as a potential therapy and its widespread availability as a nutritional supplement.

Johri AM, et al. Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome. Nutr Metab (Lond) 19, 26 (2022). https://doi.org/10.1186/s12986-022-00661-9

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4. Daily Supplementation of Vit D Improves Heart Failure Symptoms in Patients with Low Serum Vit D Status

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels are common in patients with chronic heart failure (HF) and are associated with increased mortality risk. This study aimed to establish the safety and efficacy of oral vitamin D3 (cholecalciferol) supplementation and its effect on endothelial and ventricular function in patients with stable HF.

METHODS: This study was an investigator-initiated, multicenter, prospective, randomized, placebo-controlled trial. Seventy-three HF patients with 25OHD levels < 75 nmol/L (30 ng/mL) were randomized to receive 4000 IU vitamin D daily or a placebo for 6 months. The primary endpoint was a change in endothelial function between the baseline and after 6 months as assessed using EndoPAT. Secondary endpoints included changes in echocardiographic parameters and differences in quality of life (6-min walking test and New York Heart Association functional status) at 6 months.

RESULTS: There were no adverse events in either group during the study period. Vitamin D supplementation did not improve endothelial dysfunction (EndoPAT: baseline, 1.19 ± 0.4 vs 6 months later, 1.22 ± 0.3, P = .65). However, patients’ blood pressure, 6-min walking distance, and EQ-5D questionnaire scores improved after vitamin D treatment. In addition, a significant reduction in the left atrial diameter was observed.

CONCLUSION: A daily vitamin D dose of 4000 IU for chronic HF appears to be safe. This dosage did not improve endothelial function but did improve the 6-min walk distance, symptoms, and left atrial diameter at 6 months.

Woo JS, et al. Effect of vitamin D on endothelial and ventricular function in chronic heart failure patients: A prospective, randomized, placebo-controlled trial. Medicine (Baltimore). 2022 Jul 22;101(29):e29623.doi: 10.1097/MD.0000000000029623.

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5. High-Dose Vit D Supplementation Potentially Prolongs the Honeymoon Phase in Kids with New-Onset Type 1 Diabetes

ABSTRACT: The publication of our recent randomized controlled trial (RCT) showing that vitamin D could protect the β-cells during the honeymoon phase of type 1 diabetes (T1D) has led to calls for guidance for vitamin D supplementation during the critical phase of type 1 diabetes. Prolonging the partial clinical remission (PR) phase of TID improves glycemic control and reduces long-term complications of T1D. This RCT randomized 36 children and adolescents to either receive vitamin D2 (ergocalciferol, given as 50,000 international units per week for 2 months and then every other week for 10 months) or a placebo.

The results showed that vitamin D significantly decreased the temporal rise in both hemoglobin A1c at a mean rate of changes of 0.14% every 3 months versus 0.46% every 3 months for the placebo group (p=0.044); and in the functional marker of PR, the insulin-dose adjusted A1c at a mean rate of change of 0.30% every 3 months versus 0.77% every 3 months for the placebo group, (p=0.015). We recommend a baseline estimation of 25(OH)D concentration at the time of diagnosis of T1D, and to begin vitamin D supplementation if serum 25(OH)D concentration is <30 ng/mL, to maintain serum 25(OH)D concentrations between 30-60 ng/mL.

If serum 25(OH)D concentration is >30 ng/mL, monitor vitamin D status with serial 25(OH)D estimations; and initiate vitamin D supplementation if serum 25(OH)D concentrations drop to <30 ng/mL. Continue vitamin D supplementation for at least one year to ensure optimal benefit from vitamin D supplementation during the partial clinical remission phase of type 1 diabetes.

Nwosu BU. Guidance for high-dose vitamin D supplementation for prolonging the honeymoon phase in children and adolescents with new-onset type 1 diabetes. Front Endocrinol (Lausanne). 2022 Aug 18;13:974196. doi: 10.3389/fendo.2022.974196. eCollection 2022.

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6. Ashwagandha Extract Improves General Well-Being and Sexual Performance in Adult Males

BACKGROUND AND AIM: In Ayurveda, ashwagandha is a popular plant for promoting youthful energy, longevity, and overall well‐being. It is also an excellent aphrodisiac herb that aids in the improvement and maintenance of normal sexual health. The present study aims to evaluate the effect of ashwagandha root extract on improving sexual health in adult males.

METHODS: In this 8‐week randomized, double‐blind, placebo‐controlled study, we investigated the aphrodisiac property of an ashwagandha root extract in adult males. Fifty participants with lower sexual desire were randomly allocated to take 300 mg of ashwagandha root extract or placebo capsules twice daily. Outcomes were measured using the derogatis interview for sexual functioning‐male (DISF‐M) questionnaire, serum testosterone, serum prolactin, and short‐form survey—36 quality of life questionnaire before and after the intervention.

RESULTS: Compared to placebo, ashwagandha root extract supplementation was associated with a statistically significant increase in the total DISF‐M scores (mean difference −9.8; 95% confidence interval, −10.73 to −8.87; p < 0.0001; t‐test). It was also associated with a statistically significant increase in serum testosterone levels (−66.52; −80.70 to −52.34; p < 0.0001; t‐test). However, the prolactin level did not change after intervention in both the ashwagandha and placebo groups (−1.06; −2.78 to 0.66; p > 0.05).

CONCLUSION: These findings suggest that ashwagandha demonstrated a significant subjective perception of sexual well‐being and assisted in increasing serum testosterone levels in the participants.

Chauhan S, et al. Effect of standardized root extract of ashwagandha (Withania somnifera) on well‐being and sexual performance in adult males: A randomized controlled trial. Health Sci Rep. 2022 Jul; 5(4): e741. Published online 2022 Jul 20. doi: 10.1002/hsr2.741

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7. Berberine and Fenugreek Combo Improves Metabolic Parameters in Type 2 Diabetes Patients

BACKGROUND: Type 2 Diabetes mellitus is one of the most common chronic diseases in the world and has many complications. Due to the importance of using alternative therapies in managing symptoms of this disease, the present study was designed and conducted to investigate the effect of co-supplementation of berberine and fenugreek in patients with type 2 diabetes mellitus.

METHODS: A randomized controlled clinical trial was conducted on 50 patients with type 2 diabetes mellitus. Participants were randomized in the intervention group, which received 3 capsules/day of 500 mg (300 mg of berberine + 200 mg of fenugreek seed powder) or placebo for 12 weeks. Biochemical and anthropometric variables were measured at the beginning and end of the study.

RESULTS: We observed that fasting insulin, HbA1C, and hs-CRP significantly decreased in the intervention group compared to the baseline. The mean difference in insulin resistance (-0.32 vs. 0.15), fasting blood sugar (-14.40 vs. 1.68), and fasting insulin (- 2.18 vs. 1.34) were clinically significant in comparison to the control group. Almost all domains of SF-12 scores were significantly higher in the intervention group than in the placebo group.

CONCLUSIONS: The combination of berberine and fenugreek seed can improve cardio-metabolic status in patients with diabetes and support the anti-diabetic and anti-inflammatory role of herb in the improvement of quality of life.

Nematollahi S, et al. The effect of berberine and fenugreek seed co-supplementation on inflammatory factor, lipid and glycemic profile in patients with type 2 diabetes mellitus: a double-blind controlled randomized clinical trial. Diabetol Metab Syndr. 2022 Aug 23;14(1):120. doi: 10.1186/s13098-022-00888-9.

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8. Vitamin B12 Ointment May Improves Radiodermatitis

ABSTRACT: Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis.

This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis.

The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-β in the skin samples. The pathways involved in the effects of the treatment were identified by analyzing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.

Zhao YC, et al. The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model. Int Wound J. 2023 Feb;20(2):516-528. doi: 10.1111/iwj.13899. Epub 2022 Aug 25.

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8. Six-Month Krill Oil Supplementation Improves Pain, Stiffness and Function in Patients with Osteoarthritis

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain and disability worldwide. Treatment generally focuses on symptom relief through nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, which may incur side effects. Krill oil, rich in anti-inflammatory long-chain (LC) omega-3 ( ω-3) PUFAs and astaxanthin, may be a safe and effective alternative treatment.

OBJECTIVES: This study sought to investigate the effects of a commercially available krill oil supplement on knee pain in adults with mild to moderate knee OA. Secondary outcomes were knee stiffness; physical function; NSAID use; Omega-3 Index; and lipid, inflammatory, and safety markers.

METHODS: Healthy adults (n = 235, 40-65 y old, BMI >18.5 to <35 kg/m2), clinically diagnosed with mild to moderate knee OA, regular knee pain, and consuming <0.5 g/d LC ω-3 PUFAs, participated in a 6-mo double-blind, randomized, placebo-controlled, multicenter trial. Participants consumed either 4 g krill oil/d (0.60 g EPA/d, 0.28 g DHA/d, 0.45 g astaxanthin/d) or placebo (mixed vegetable oil). Knee outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) numeric scale (normalized to scores of 0-100). Outcomes were assessed at baseline, 3 mo, and 6 mo.

RESULTS: Omega-3 Index increased with the krill oil supplement compared with placebo (from 6.0% to 8.9% compared with from 5.5% to 5.4%, P < 0.001). Knee pain score improved in both groups with greater improvements for krill oil than for placebo (difference in adjusted mean change between groups at 6 mo: -5.18; 95% CI: -10.0, -0.32; P = 0.04). Knee stiffness and physical function also had greater improvements with krill oil than with placebo (difference in adjusted mean change between groups at 6 mo: -6.45; 95% CI: -12.1, -0.9 and -4.67; 95% CI: -9.26, -0.05, respectively; P < 0.05). NSAID use, serum lipids, and inflammatory and safety markers did not differ between groups.

CONCLUSIONS: Krill oil was safe to consume and resulted in modest improvements in knee pain, stiffness, and physical function in adults with mild to moderate knee OA.This trial was registered at clinicaltrials.gov as NCT03483090.

Stonehouse W, et al. Krill oil improved osteoarthritic knee pain in adults with mild to moderate knee osteoarthritis: a 6-month multicenter, randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2022 Sep 2;116(3):672-685. doi: 10.1093/ajcn/nqac125.

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9. Children with Peanut Allergy may Also be Allergic to One or More Legumes

BACKGROUND: Legume consumption has increased during the two past decades. In France, legumes are responsible for 14.6% of food-related anaphylaxis in children, with peanut as the main allergen (77.5%). Few studies have demonstrated cross-reactivities between peanut and other legumes. The aim of this study was to determine prevalence and relevance of sensitization to legumes in peanut-allergic children.

METHODS: All children, aged of 1–17 years, admitted to the Pediatric Allergy Department of the University Hospital of Nancy between January 1, 2017 and February 29, 2020 with a confirmed peanut allergy (PA) and a documented consumption or sensitization to at least one other legume were included. Data were retrospectively collected regarding history of consumption, skin prick tests, specific immunoglobulin E (IgE), prior allergic reactions, and oral food challenges for each legume.

RESULTS: Among the 195 included children with PA, 122 were sensitized to at least one other legume (63.9%). Main sensitizations were for fenugreek (N = 61, 66.3%), lentil (N = 38, 42.2%), soy (N = 61, 39.9%), and lupine (N = 63, 34.2%). Among the 122 sensitized children, allergy to at least one legume was confirmed for 34 children (27.9%), including six children who had multiple legume allergies (4.9%). Lentil, lupine, and pea were the main responsible allergens. Half of allergic reactions to legumes other than peanuts were severe.

CONCLUSION: The high prevalence of legume sensitization and the frequent severe reactions reported in children with PA highlight that tolerated legume consumption should be explored for each legume in the case of PA, and sensitization should be investigated if not.

Muller T, et al. Relevance of sensitization to legumes in peanut-allergic children. Pediatr Allergy Immunol. 2022 Sep;33(9):e13846.doi: 10.1111/pai.13846.

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10. Hydrogen Inhalation and Hydrogen Water May Reduce Breath Alcohol Concentration and Hangover Symptoms

BACKGROUND: Alcohol-induced hangover represents a significant, yet understudied, global hazard and a large socioeconomic burden.

OBJECTIVE: The aim of this study was to investigate the effects of hydrogen on relieving drinking and hangover symptoms in 20 healthy volunteers.

METHODS: In this pilot, randomized, double-blinded, placebo-controlled, matched, crossover interventional trial, participants were matched into pairs and randomly assigned. Study group 1 inhaled placebo air for 1 h, followed by drinking 100 mL liquor (40% alcohol) within 10 min, and then pure water. Study group 2 inhaled a mixture of hydrogen and oxygen gas for 1 h, followed by drinking 100 mL liquor within 10 min, and then hydrogen dissolved in water. On a second intervention day (crossover) ≥1 wk later, study-group subjects were switched to the opposite order. Breath alcohol concentration (BrAC), hangover severity, and cognitive scores were measured.

RESULTS: The BrACs within the hydrogen group were significantly lower than those within the placebo group after 30 min, 60 min, and 90 min (P < 0.05). The hydrogen group reported having fewer hangover symptoms compared with the placebo group (placebo: 77% of symptoms absent, 19.7% of mild symptoms, 2.7% of moderate symptoms, 0.7% of severe symptoms; hydrogen: 88.6% of symptoms absent, 10% of mild symptoms, 1.3% of moderate symptoms, 0% of severe symptoms; P < 0.001). Hydrogen treatment improved cognitive testing scores (P < 0.05), including attention and executive functions. Furthermore, consumption of hydrogen was negatively (β = −13.016; 95% CI: −17.726, −8.305; P < 0.001) and female sex was positively (β = 22.611; 95% CI: 16.226, 28.997; P < 0.001) correlated with increased BrACs. Likewise, the consumption of hydrogen was negatively (OR: 0.035; 95% CI: 0.007, 0.168; P < 0.001) while female sex was positively (OR: 28.838; 95% CI: 5.961, 139.506; P < 0.001) correlated with the severity of hangover symptoms.

CONCLUSIONS: Hydrogen decreases BrACs and relieves the symptoms of hangovers. This trial was registered at the China Clinical Trial Registry

Lv X, et al. Hydrogen intake relieves alcohol consumption and hangover symptoms in healthy adults: a randomized and placebo-controlled crossover study. Am J Clin Nutr. 2022 Sep 16;nqac261. doi: 10.1093/ajcn/nqac261. Online ahead of print.

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11. Vitamin C Supplementation for Pregnant Smokers May Minimize the Negative Impacts of Smoking on Offspring’s Respiratory Health

IMPORTANCE: Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed.

OBJECTIVE: To assess whether vitamin C supplementation in pregnant smokers is associated with increased and/or improved airway function in their offspring at age 5 years and whether vitamin C decreases the occurrence of wheeze.

DESIGN, SETTING AND PARTICIPANTS: This study followed up the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) double-blind, placebo-controlled randomized clinical trial conducted at 3 centers in the US (in Oregon, Washington, and Indiana) between 2012 and 2016. Investigators and participants remain unaware of the treatment assignments. Forced expiratory flow measurements at age 5 years were completed from 2018 to 2021.

INTERVENTIONS: Pregnant smokers were randomized to vitamin C (500 mg/d) or placebo treatment.

MAIN OUTCOMES AND MEASURES: The primary outcome was the prespecified measurement of FEF between 25% and 75% expired volume (FEF25-75) by spirometry at age 5 years. Secondary outcomes included FEF measurements at 50% and 75% of expiration (FEF50 and FEF75), forced expiratory volume in 1 second (FEV1), and occurrence of wheeze.

RESULTS: Of the 251 pregnant smokers included in this study, 125 (49.8%) were randomized to vitamin C and 126 (50.2%) were randomized to placebo. Of 213 children from the VCSIP trial who were reconsented into this follow-up study, 192 (90.1%) had successful FEF measurements at age 5 years; 212 (99.5%) were included in the analysis of wheeze.

Analysis of covariance demonstrated that offspring of pregnant smokers allocated to vitamin C 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). Mean (SE) measurements were also significantly increased by 14.1% for FEF50 (1.59 [0.04] vs 1.39 [0.04] L/s; adjusted mean difference, 0.20 [95% CI, 0.11-0.30]; P < .001), 25.9% for FEF75 (0.79 [0.02] vs 0.63 [0.02] L/s; 0.16 [95% CI, 0.11-0.22]; P < .001), and 4.4% for FEV1 (1.13 [0.02] vs 1.09 [0.02] L; 0.05 [95% CI, 0.01-0.09]; P = .02). In addition, offspring of pregnant smokers randomized to vitamin C had significantly decreased wheeze (28.3% vs 47.2%; estimated odds ratio, 0.41 [95% CI, 0.23-0.74]; P = .003).

CONCLUSIONS AND RELEVANCE: In this follow-up study of offspring of pregnant smokers randomized to vitamin C vs placebo, vitamin C supplementation during pregnancy resulted in significantly increased airway function of offspring at age 5 years and significantly decreased the occurrence of wheeze. These findings suggest that vitamin C supplementation for pregnant smokers may decrease the effects of smoking in pregnancy on childhood airway function and respiratory health.

McEnvoy CT, et al. Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial. JAMA Pediatr. 2023 Jan 1;177(1):16-24.  doi: 10.1001/jamapediatrics.2022.4401.

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