Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.

Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.

Long-chain omega-3 fatty acids, selenium, and mercury in relation to sleep duration and sleep quality: findings from the CARDIA study.

PURPOSE: To examine the associations of long-chain omega-3 polyunsaturated fatty acids (LCω3PUFA) intake with sleep quality and duration in a cohort of American young adults, and to explore whether the associations of interest are modified by selenium (Se) and/or mercury (Hg) status. METHODS: The study sample consisted of 3964 men and women from the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) study, aged 25.0 ± 3.6 at baseline. Intake of LCω3PUFA was assessed using an interviewer-administered dietary history questionnaire at baseline (1985-1986), Y7 (1992-1993), and Y20 (2005-2006). Toenail Se and Hg concentrations were quantified at Y2 (1987-1988). The outcomes were self-reported sleep quality and sleep duration measured by one question for each at Y15 (2000-2001) and Y20. Generalized estimating equation was used to examine the association between cumulative average intake of LCω3PUFA and sleep measures. Restricted cubic spline was performed to explore the potential non-linear associations of interest. Se and Hg were dichotomized by their median values to examine the potential effect modification of Se and/or Hg. RESULTS: We did not observe any significant associations (linear or non-linear) of LCω3PUFA intake with either sleep quality or duration. Also, no significant association was observed in any subgroup classified by toenail Se and/or Hg concentrations. Similarly, sensitivity analysis indicated that the null associations between LCω3PUFA intake and sleep quality or duration persisted across subgroups classified by race, gender, obesity, or having small children. CONCLUSION: Findings from this longitudinal analysis did not support the hypothesis that LCω3PUFA intake is associated with sleep quality or sleep duration.

Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study.

STUDY OBJECTIVES: As an antagonist of calcium (Ca), magnesium (Mg) has been implicated in the regulation of sleep. We aimed to examine the longitudinal associations of Mg intake and Ca-to-Mg intake ratio (Ca:Mg) with sleep quality and duration. METHODS: The study sample consisted of 3,964 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary and supplementary intake of Mg were obtained using the CARDIA Dietary History at baseline (1985-1986), exam years 7 and 20. Self-reported sleep outcomes were measured at years 15 and 20. Sleep quality was rating from 1 (very good) to 5 (very bad). We categorized sleep duration to <7, 7-9, and >9 h. Generalized estimating equation was used to examine the associations of interest as repeated measures at the two time points. RESULTS: After adjustment for potential confounders, Mg intake was borderline associated with better sleep quality [highest quartile (Q4) vs. intake quartile (Q1): odds ratio (OR) = 1.23; 95% CI = 0.999, 1.50, ptrend = 0.051]. Participants in Q4 were also less likely to have short sleep (<7 h) compared to those in Q1 (OR = 0.64; 95% CI = 0.51, 0.81, ptrend = 0.012). The observed association with short sleep persisted among participants without depressive disorders (Q4 vs. Q1: OR = 0.64; 95% CI = 0.49, 0.82, ptrend < 0.001), but not among individuals with depressive disorder. Ca:Mg was not associated with either outcomes, regardless of depression status. CONCLUSIONS: Mg intake was associated with both sleep outcomes in this longitudinal analysis. Randomized controlled trials with objective measures of sleep are warranted to establish the potential causal inference.

Influence of Zinc on the Acute Changes in Erythropoietin and Proinflammatory Cytokines with Hypoxia.

Baranauskas, Marissa N., Joseph Powell, Alyce D. Fly, Bruce J. Martin, Timothy D. Mickleborough, Hunter L. Paris, and Robert F. Chapman. Influence of zinc on the acute changes in erythropoietin and proinflammatory cytokines with hypoxia. High Alt Med Biol. 22: 148-156, 2021. Background: Considerable, unexplained, interindividual variability characterizes the erythropoietin (EPO) response to hypoxia, which can impact hematological acclimatization for individuals sojourning to altitude. Zinc supplementation has the potential to alter EPO by attenuating increases in inflammation and oxidative stress. Yet, the application of such an intervention has not been evaluated in humans. In this proof-of-concept study, we aimed to evaluate the EPO and inflammatory responses to acute hypoxia in human participants following chronic zinc supplementation. Methods: Nine physically active participants (men n = 5, women n = 4, age 28 ± 4 years, height 176 ± 11 cm, mass 77 ± 21 kg) were exposed to 12 hours of normobaric hypoxia simulating an altitude of 3,000 m (FiO2 = 0.14) before and after 8 weeks of supplementation with 40 mg/day of elemental zinc from picolinate. Blood samples for subsequent analysis of serum zinc, EPO, superoxide dismutase (extracellular superoxide dismutase [EC-SOD]), C-reactive protein (CRP), and proinflammatory cytokines were obtained pre- and postsupplementation and exposure to hypoxia. Results: After zinc supplementation, EPO increased by 64.9 ± 36.0% (mean ± standard deviation) following 12 hours of hypoxia, but this response was not different from presupplementation (70.8 ± 46.1%). Considerable interindividual (range: -1% to +208%) variability was apparent in the acute EPO response. While most markers of inflammation did not change with hypoxia, interleukin-6 concentrations increased from 1.17 ± 0.05 to 1.97 ± 0.32 pg/ml during the final 6 hours. The acute EPO response at 12 hours was not related to changes in serum zinc, EC-SOD, CRP, or proinflammatory cytokines. Conclusions: Zinc supplementation does not influence the acute EPO or inflammatory response with short-term exposure to moderate levels of normobaric hypoxia (3,000 m) in apparently healthy young adults.

Association of herbal/botanic supplement use with quality of life, recurrence, and survival in newly diagnosed stage II colon cancer patients: A 2-y follow-up study.

OBJECTIVES: Our objective was to investigate the association between herbal/botanic supplement use and perceived quality of life (QoL), cancer recurrence, and all-cause mortality in colon cancer patients. METHODS: Patients (n = 453) newly diagnosed with stage II adenocarcinoma of the colon between 2009 and 2011 were recruited from the North Carolina Central Cancer Registry. Data including demographic variables, herbal medicine use and frequency, lifestyle, diet, cancer treatment, and QoL were collected by interviews at diagnosis (baseline) and 1 and 2 y after diagnosis. Mortality information was obtained via the National Death Index. The Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and Medical Outcomes Short Form 12 (SF-12) were used to evaluate QoL. RESULTS: At baseline, herbal/botanic supplement users were more likely to have a healthier lifestyle than non-users, including more physical activity (P <0.01), more fruit and vegetable consumption (P = 0.01), less smoking (P <0.01), and less energy intake from fat (P = 0.02). After adjustment for potential confounders, no significant association was found between herbal/botanic supplement use and QoL assessed by FACT-C and SF-12. Similarly, herbal/botanic supplement use was not associated with the risk of recurrence, all-cause mortality or the combined. CONCLUSION: In this study, patients with stage II colon cancer using herbal/botanic supplements had no significant improvement in their QoL and no difference in odds of colon cancer recurrence and all-cause mortality over 2 y after diagnosis compared with those who did not use herbs/botanicals. Further studies are warranted to confirm the findings and to focus on types of herbal/botanic supplements.

Fish Oil Supplementation and Quality of Life in Stage II Colorectal Cancer Patients: A 24-Month Follow-Up Study.

Research suggests that cancer survivors have an interest in lifestyle changes following a diagnosis. However, few studies have prospectively investigated whether these changes result in positive outcomes. The objective of this study was to examine the associations between fish oil supplementation and quality of life (QoL), cancer recurrence, and all-cause mortality in Stage 2 colorectal cancer (CRC) patients following diagnosis. Four hundred fifty-three patients were enrolled from the North Carolina Cancer Registry from 2009 to 2011. Data on demography, treatment, and health behaviors were collected at diagnosis, 12-, and 24 mo postdiagnosis. Generalized estimating equations were performed to examine fish oil supplementation in relation to QoL, recurrence, and all-cause mortality. An increase in fish oil supplementation over 24 mo postdiagnosis was associated with an increase in the physical component score of the 12-item Medical Outcomes Short Form (ß = 2.43, 95% CI: 0.10-4.76). Supplementation showed no association with the Functional Assessment of Cancer-Colorectal, cancer recurrence or mortality across the 24-mo follow-up. This study suggests that fish oil supplementation may improve symptom-related QoL (i.e., physical functioning) in Stage 2 CRC patients following diagnosis. Future research should address the dose-dependent effects of this relationship.

Conjugated linoleic acid's lack of attenuation of hyperpnea-induced bronchoconstriction in asthmatic individuals in the short term.

PURPOSE: Conjugated linoleic acid (CLA) has been reported to modify the inflammatory response associated with allergic airway disease, primarily in animal models. To extend these observations to humans, the effect of short-term CLA supplementation on the severity of exercise-induced bronchoconstriction (EIB) was investigated in asthmatics. METHODS: Six subjects with physician-diagnosed asthma and EIB began the study on their usual diet, to which was added 4.8 g CLA/d for 8 wk. Pulmonary-function tests were administered before and after eucapnic voluntary hyperventilation (EVH) challenge at the commencement (Week 0) and conclusion of the treatment period (Week 8). Pre- and 90 min post-EVH challenge, urine was assayed for the presence of cysteinyl leukotrienes (LT) C4-E4 and 9α, 11ß-prostaglandin (PG) F2. RESULTS: Pre- to post-EVH forced expiratory volume in 1 s (FEV1) did not significantly differ (p > .05) from Week 8 to Week 0. The pre- to post-EVH decline in FEV1 at Week 8 (-29.6% ± 6.6%) was not significantly different (p > .05) from that at Week 0 (-32.0% ± 5.5%). Area under the curve of FEV1 plotted against time from zero to 60 min (AUC0-60) was unaltered at Week 8 (-931% ± 350% change per minute) compared with Week 0 (-1,090% ± 270% change per minute). CLA supplementation did not alter forced midexpiratory flow, forced vital capacity (FVC), or FEV1/FVC. In addition, post-EVH urinary LTC4-E4 and 9α, 11ß-PGF2 were unchanged after CLA supplementation. CONCLUSION: Daily supplementation of 4.8 g CLA for 8 wk does not attenuate airway inflammation or hyperpnea-induced bronchoconstriction in asthmatic individuals.

Randomized controlled trial of fish oil and montelukast and their combination on airway inflammation and hyperpnea-induced bronchoconstriction.

BACKGROUND: Both fish oil and montelukast have been shown to reduce the severity of exercise-induced bronchoconstriction (EIB). The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH) in asthmatics. METHODS: In this model of EIB, twenty asthmatic subjects with documented hyperpnea-induced bronchoconstriction (HIB) entered a randomized double-blind trial. All subjects entered on their usual diet (pre-treatment, n = 20) and then were randomly assigned to receive either one active 10 mg montelukast tablet and 10 placebo fish oil capsules (n = 10) or one placebo montelukast tablet and 10 active fish oil capsules totaling 3.2 g EPA and 2.0 g DHA (n = 10) taken daily for 3-wk. Thereafter, all subjects (combination treatment; n = 20) underwent another 3-wk treatment period consisting of a 10 mg active montelukast tablet or 10 active fish oil capsules taken daily. RESULTS: While HIB was significantly inhibited (p<0.05) by montelukast, fish oil and combination treatment compared to pre-treatment, there was no significant difference (p>0.017) between treatment groups; percent fall in forced expiratory volume in 1-sec was -18.4 ± 2.1%, -9.3±2.8%, -11.6 ± 2.8% and -10.8 ± 1.7% on usual diet (pre-treatment), fish oil, montelukast and combination treatment respectively. All three treatments were associated with a significant reduction (p<0.05) in F(E)NO, exhaled breathe condensate pH and cysteinyl-leukotrienes, while the fish oil and combination treatment significantly reduced (p<0.05) urinary 9α, 11ß-prostaglandin F(2) after EVH compared to the usual diet; however, there was no significant difference (p>0.017) in these biomarkers between treatments. CONCLUSION: While fish oil and montelukast are both effective in attenuating airway inflammation and HIB, combining fish oil with montelukast did not confer a greater protective effect than either intervention alone. Fish oil supplementation should be considered as an alternative treatment for EIB. TRIAL REGISTRATION: ClinicalTrials.gov NCT00676468.

Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma.

BACKGROUND: Previous research has shown that diet can modify the bronchoconstrictor response to exercise in asthmatic subjects. OBJECTIVE: Determine the effect of ascorbic acid supplementation on pulmonary function and several urinary markers of airway inflammation in asthmatic subjects with exercise-induced bronchoconstriction (EIB). METHODS: Eight asthmatic subjects with documented EIB participated in a randomized, placebo controlled double-blind crossover trial. Subjects entered the study on their usual diet and were placed on either 2 weeks of ascorbic acid supplementation (1500 mg/day) or placebo, followed by a 1-week washout period, before crossing over to the alternative diet. Pre- and post-exercise pulmonary function, asthma symptom scores, fraction of exhaled nitric oxide (FENO), and urinary leukotriene (LT) C4-E4 and 9alpha, 11beta-prostagladin (PG) F2] were assessed at the beginning of the trial (usual diet) and at the end of each treatment period. RESULTS: The ascorbic acid diet significantly reduced (p < 0.05) the maximum fall in post-exercise FEV1 (-6.4 +/- 2.4%) compared to usual (-14.3 +/- 1.6%) and placebo diet (-12.9 +/- 2.4%). Asthma symptoms scores significantly improved (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. Post-exercise FENO, LTC4-E4 and 9alpha, 11beta-PGF2 concentration was significantly lower (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. CONCLUSION: Ascorbic acid supplementation provides a protective effect against exercise-induced airway narrowing in asthmatic subjects.

Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma.

BACKGROUND: Previous research has demonstrated that fish oil supplementation has a protective effect on exercise-induced bronchoconstriction (EIB) in elite athletes, which may be attributed to its antiinflammatory properties. Since EIB in asthma involves proinflammatory mediator release, it is feasible that fish oil supplementation may reduce the severity of EIB in asthmatic subjects. STUDY OBJECTIVES: To determine the efficacy of fish oil supplementation on severity of EIB in subjects with asthma. DESIGN: Randomized, double-blind, crossover study. SETTING: Lung function and exercise testing in a university research laboratory. PATIENTS AND MEASUREMENTS: Sixteen asthmatic patients with documented EIB entered the study on their normal diet and then received either fish oil capsules containing 3.2 g of eicosapentaenoic acid and 2.0 g of docohexaenoic acid (fish oil diet, n = 8) or placebo capsules (placebo diet, n = 8) daily for 3 weeks. At the beginning of the study (normal diet) and at the end of each treatment phase, the following pre-exercise and postexercise measures were assessed: (1) pulmonary function; (2) induced sputum differential cell count percentage and proinflammatory eicosanoid metabolite (leukotriene C4 [LTC4]-leukotriene E4 [LTE4] and prostaglandin D2 [PGD2]) and cytokine (interleukin [IL]-1beta and tumor necrosis factor [TNF]-alpha) concentrations; and (3) eicosanoid metabolites leukotriene B4 (LTB4) and leukotriene B5 (LTB(5)) generation from activated polymorphonuclear leukocytes (PMNLs). RESULTS: On the normal and placebo diet, subjects exhibited EIB. However, the fish oil diet improved pulmonary function to below the diagnostic EIB threshold, with a concurrent reduction in bronchodilator use. Induced sputum differential cell count percentage and concentrations of LTC4-LTE4, PGD2, IL-1beta, and TNF-alpha were significantly reduced before and following exercise on the fish oil diet compared to the normal and placebo diets. There was a significant reduction in LTB4 and a significant increase in LTB5 generation from activated PMNLs on the fish oil diet compared to the normal and placebo diets. CONCLUSION: Our data suggest that fish oil supplementation may represent a potentially beneficial nonpharmacologic intervention for asthmatic subjects with EIB.