Patricia A. Cassano

Randomised controlled studies evaluating vitamin D supplementation in pregnancy or early childhood for preventing childhood asthma have yielded inconclusive results. Previous systematic reviews of vitamin D for asthma prevention focused on studies comparing vitamin D to placebo or studies intervening in pregnancy, limiting the body of evidence. Primary: to evaluate the efficacy of any vitamin D supplementation and high-dose vitamin D supplementation in early life, including the prenatal period, for preventing asthma in children. Secondary: to assess the efficacy of vitamin D supplementation: • for preventing asthma in children at risk of vitamin D deficiency at the start of the trial or whose mothers were at risk; • by intervention timing and the cumulative dose administered; • in preventing factors associated with early childhood asthma, including atopic dermatitis, respiratory tract infections, sensitisation to allergens, and airway inflammation. We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and the Cochrane Airways and Skin Trial Registers. We checked the reference lists of relevant systematic reviews and meta-analyses. We contacted authors to obtain additional study information as needed. Date of last search: October 2023. We included randomised controlled studies comparing higher versus lower/standard dose vitamin D (≤ 400 international units (IU)/day) or any vitamin D versus placebo/no treatment in generally healthy pregnant or lactating women or children up to five years of age that evaluated childhood asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, and airway inflammation. We excluded trials recruiting populations with pre-existing conditions. We followed standard Cochrane methodological procedures, including using Cochrane's Screen4Me workflow. We considered participants rather than events as the unit of analysis, performed fixed-effect meta-analysis, and reported risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) for four comparisons: (1) any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women; (2) any vitamin D versus placebo/no supplementation in infants or children; (3) high versus low/standard dose vitamin D in pregnant or breastfeeding women; (4) high versus low/standard dose vitamin D in infants or children. Our outcomes were: asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, airway inflammation, and adverse events. We narratively described results that could not be meta-analysed. We used the Cochrane risk of bias tool (RoB) to assess bias in the studies. We used GRADE to assess the certainty of the evidence. We included 18 studies involving a total of 10,611 participants, of which 16 contributed data to meta-analyses. Studies were conducted around the world, with most taking place in higher-income countries. The dose and frequency of vitamin D ranged from 200 IU/day to 100,000 IU bolus quarterly, and the duration of supplementation ranged from 28 days to two years. Comparison 1. Any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women (4 studies) Compared to placebo or no supplementation, any vitamin D given to pregnant or breastfeeding women may reduce the risk of early childhood asthma (RR 0.17, 95% CI 0.05 to 0.61; 1 study, 236 participants; low-certainty evidence) and likely has little to no effect on childhood airway infections (RR 1.00, 95% CI 0.97 to 1.04; 3 studies, 1564 participants; moderate-certainty evidence). The evidence is very uncertain for wheeze, atopic dermatitis, allergic sensitisation, airway inflammation, or adverse events. Comparison 2. Any vitamin D versus placebo/no supplementation in infants or children (5 studies) Compared to placebo or no supplementation, any vitamin D given to infants or children may have little to no effect on childhood wheeze (RR 0.89, 95% CI 0.68 to 1.16; 2 studies, 431 participants; low-certainty evidence), atopic dermatitis (RR 1.01, 95% CI 0.80 to 1.28; 2 studies, 448 participants; low-certainty evidence), airway infections (RR 0.92, 95% CI 0.83 to 1.01; 2 studies, 500 participants; low-certainty evidence), allergic sensitisation (RR 2.25, 95% CI 0.60 to 8.50; 1 study, 228 participants; low-certainty evidence), or airway inflammation measured by eosinophil counts (RR 1.06, 95% CI 0.65 to 1.74; 1 study, 226 participants; low-certainty evidence). The evidence is very uncertain for asthma and adverse events. Comparison 3. High versus low/standard dose vitamin D in pregnant or breastfeeding women (4 studies) Compared to low/standard dose, high-dose vitamin D given to pregnant or breastfeeding women likely reduces the risk of childhood wheeze (RR 0.79, 95% CI 0.64 to 0.98; 3 studies, 1439 participants; moderate-certainty evidence), but likely results in little to no difference in childhood asthma, although the direction and magnitude of effect is similar to that for wheeze (RR 0.81, 95% CI 0.63 to 1.04; 2 studies, 1355 participants; moderate-certainty evidence). Compared to low/standard dose, high-dose vitamin D in pregnancy likely has little to no effect on childhood atopic dermatitis (RR 0.91, 95% CI 0.75 to 1.11; 3 studies, 1439 participants; moderate-certainty evidence), airway infections (RR 0.95, 95% CI 0.82 to 1.11; 3 studies, 1441 participants; moderate-certainty evidence), or allergic sensitisation (RR 1.01, 95% CI 0.87 to 1.18; 2 studies, 1110 participants; moderate-certainty evidence). The evidence is very uncertain for adverse events. No studies evaluated airway inflammation. Comparison 4. High versus low/standard dose vitamin D in infants or children (7 studies) Compared to low/standard dose, high-dose vitamin D given to infants or children may slightly reduce airway infections (RR 0.94, 95% CI 0.90 to 0.98; 6 studies, 2385 participants; low-certainty evidence) but may have little...

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have anti-inflammatory properties and may benefit lung health. Objectives: Investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in adults of diverse races/ethnicities from general population cohorts. Methods: Complementary study designs: (1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV ₁ and FVC measures in the National Heart, Lung, and Blood Institute Pooled Cohorts Study, and (2) two-sample Mendelian Randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid concentrations were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for docosahexaenoic acid (DHA). One standard deviation higher DHA was associated with an attenuation of 1.8 mL/year for FEV ₁ (95% confidence interval [CI] 1.3–2.2) and 2.4 mL/year for FVC (95% CI 1.9–3.0). One standard deviation higher DHA was also associated with a 9% lower incidence of spirometry-defined airway obstruction (95% CI 0.86–0.97). DHA associations persisted across sexes, smoking histories, and Black, white and Hispanic participants, with the largest magnitude associations in former smokers and Hispanics. The MR study showed positive associations of genetically predicted omega-3 fatty acids with FEV ₁ and FVC, with statistically significant findings across multiple MR methods. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher circulating omega-3 fatty acids, especially DHA, on lung health.

Aims: The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF). Methods and results: Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine–Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07–1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27–1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking. Conclusion: Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV₁)] and examined genetic and nongenetic factors associated with ∆vitE. We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV₁ was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGA^ex). We used mixed-effects linear regression modeling to examine the ∆vitE–FEV₁ association. Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV₁ decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV₁ decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE–FEV₁ association was similar in never smokers (2.4-mL/y attenuated FEV₁ decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (−0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564). Greater response to vitE supplementation was associated with attenuated FEV₁ decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.

Background Arsenic is a common environmental toxin. Exposure to arsenic (particularly its inorganic form) through contaminated food and drinking water is an important public health burden worldwide, and is associated with increased risk of neurotoxicity, congenital anomalies, cancer, and adverse neurodevelopment in children. Arsenic is excreted following methylation reactions, which are mediated by folate. Provision of folate through folic acid supplements could facilitate arsenic methylation and excretion, thereby reducing arsenic toxicity. Objectives To assess the effects of provision of folic acid (through fortified foods or supplements), alone or in combination with other nutrients, in lessening the burden of arsenic‐related health outcomes and reducing arsenic toxicity in arsenic‐exposed populations. Search methods In September 2020, we searched CENTRAL, MEDLINE, Embase, 10 other international databases, nine regional databases, and two trials registers. Selection criteria Randomised controlled trials (RCTs) and quasi‐RCTs comparing the provision of folic acid (at any dose or duration), alone or in combination with other nutrients or nutrient supplements, with no intervention, placebo, unfortified food, or the same nutrient or supplements without folic acid, in arsenic‐exposed populations of all ages and genders. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included two RCTs with 822 adults exposed to arsenic‐contaminated drinking water in Bangladesh. The RCTs compared 400 µg/d (FA400) or 800 µg/d (FA800) folic acid supplements, given for 12 or 24 weeks, with placebo. One RCT, a multi‐armed trial, compared FA400 plus creatine (3 g/d) to creatine alone. We judged both RCTs at low risk of bias in all domains. Due to differences in co‐intervention, arsenic exposure, and participants' nutritional status, we could not conduct meta‐analyses, and therefore, provide a narrative description of the data. Neither RCT reported on cancer, all‐cause mortality, neurocognitive function, or congenital anomalies. Folic acid supplements alone versus placebo Blood arsenic. In arsenic‐exposed individuals, FA likely reduces blood arsenic concentrations compared to placebo (2 studies, 536 participants; moderate‐certainty evidence). For folate‐deficient and folate‐replete participants who received arsenic‐removal water filters as a co‐intervention, FA800 reduced blood arsenic levels more than placebo (percentage change (%change) in geometric mean (GM) FA800 −17.8%, 95% confidence intervals (CI) −25.0 to −9.8; placebo GM −9.5%, 95% CI −16.5 to −1.8; 1 study, 406 participants). In one study with 130 participants with low baseline plasma folate, FA400 reduced total blood arsenic (%change FA400 mean (M) −13.62%, standard error (SE) ± 2.87; placebo M −2.49%, SE ± 3.25), and monomethylarsonic acid (MMA) concentrations (%change FA400 M −22.24%, SE ± 2.86; placebo M −1.24%, SE ± 3.59) more than placebo. Inorganic arsenic (InAs) concentrations reduced in both groups (%change FA400 M −18.54%, SE ± 3.60; placebo M −10.61%, SE ± 3.38). There was little to no change in dimethylarsinic acid (DMA) in either group. Urinary arsenic. In arsenic‐exposed individuals, FA likely reduces the proportion of total urinary arsenic excreted as InAs (%InAs) and MMA (%MMA) and increases the proportion excreted as DMA (%DMA) to a greater extent than placebo (2 studies, 546 participants; moderate‐certainty evidence), suggesting that FA enhances arsenic methylation. In a mixed folate‐deficient and folate‐replete population (1 study, 352 participants) receiving arsenic‐removal water filters as a co‐intervention, groups receiving FA had a greater decrease in %InAs (within‐person change FA400 M −0.09%, 95% CI −0.17 to −0.01; FA800 M −0.14%, 95% CI −0.21 to −0.06; placebo M 0.05%, 95% CI 0.00 to 0.10), a greater decrease in %MMA (within‐person change FA400 M −1.80%, 95% CI −2.53 to −1.07; FA800 M −2.60%, 95% CI −3.35 to −1.85; placebo M 0.15%, 95% CI −0.37 to 0.68), and a greater increase in %DMA (within‐person change FA400 M 3.25%, 95% CI 1.81 to 4.68; FA800 M 4.57%, 95% CI 3.20 to 5.95; placebo M −1.17%, 95% CI −2.18 to −0.17), compared to placebo. In 194 participants with low baseline plasma folate, FA reduced %InAs (%change FA400 M −0.31%, SE ± 0.04; placebo M −0.13%, SE ± 0.04) and %MMA (%change FA400 M −2.6%, SE ± 0.37; placebo M −0.71%, SE ± 0.43), and increased %DMA (%change FA400 M 5.9%, SE ± 0.82; placebo M 2.14%, SE ± 0.71), more than placebo. Plasma homocysteine: In arsenic‐exposed individuals, FA400 likely reduces homocysteine concentrations to a greater extent than placebo (2 studies, 448 participants; moderate‐certainty evidence), in the mixed folate‐deficient and folate‐replete population receiving arsenic‐removal water filters as a co‐intervention (%change in GM FA400 −23.4%, 95% CI −27.1 to −19.5; placebo −1.3%, 95% CI −5.3 to 3.1; 1 study, 254 participants), and participants with low baseline plasma folate (within‐person change FA400 M −3.06 µmol/L, SE ± 3.51; placebo M −0.05 µmol/L, SE ± 4.31; 1 study, 194 participants). FA supplements plus other nutrient supplements versus nutrient supplements alone In arsenic‐exposed individuals who received arsenic‐removal water filters as a co‐intervention, FA400 plus creatine may reduce blood arsenic concentrations more than creatine alone (%change in GM FA400 + creatine −14%, 95% CI −22.2 to −5.0; creatine −7.0%, 95% CI −14.8 to 1.5; 1 study, 204 participants; low‐certainty evidence); may not change urinary arsenic methylation indices (FA400 + creatine: %InAs M 13.2%, SE ± 7.0; %MMA M 10.8, SE ± 4.1; %DMA M 76, SE ± 7.8; creatine: %InAs M 14.8, SE ± 5.5; %MMA M 12.8, SE ± 4.0; %DMA M 72.4, SE ±7.6; 1 study, 190 participants; low‐certainty evidence); and may reduce homocysteine concentrations to a greater extent (%change in GM FA400 + creatinine −21%, 95% CI −25.2 to −16.4; creatine −4.3%, 95% CI −9.0 to 0.7; 1 study, 204 participants; low‐certainty evidence) than creatine alone. Authors' conclusions There is moderate‐certainty evidence that FA supplements may benefit blood arsenic concentration, urinary arsenic methylation profiles, and plasma homocysteine concentration versus placebo. There is low‐certainty evidence that FA supplements plus other nutrients may benefit blood arsenic and plasma homocysteine concentrations versus nutrients alone. No studies reported on cancer, all‐cause mortality, neurocognitive function, or congenital anomalies. Given the limited number of RCTs, more studies conducted in diverse settings are needed to assess the effects of FA on arsenic‐related health outcomes and arsenic toxicity in arsenic‐exposed adults and children.

Background: Given its antioxidant activity, vitamin E is hypothesized to attenuate the age-related decline in pulmonary function. Objective: We investigated the association between change in plasma vitamin E (ΔvitE) and pulmonary function decline and examined genetic and non-genetic factors associated with ΔvitE. Design: We studied 1,144 men randomized to vitE in the Selenium and Vitamin E Cancer Prevention Trial. ΔvitE was calculated as the difference between baseline and year 3 vitE concentrations measured with gas chromatography-mass spectrometry. Pulmonary function (forced expiratory volume in the first second [FEV ₁ ]) was measured longitudinally with spirometry. We genotyped 555 participants (vitE-only arm) using the Illumina MEGA ^ex array. We examined the association of ΔvitE with annual change in FEV ₁ using mixed-effects linear regression. We also examined the association of previously reported genetic and non-genetic factors with ΔvitE. Results: Greater ΔvitE was associated with attenuated FEV ₁ decline, with stronger effects in adherent supplement responders: a 1 SD higher ΔvitE (+4 µmol/mmol free-cholesterol-adjusted α-tocopherol) attenuated FEV ₁ decline by ∼8.9 mL/year ( P =0.014). This effect size is ∼1/4 of the effect of one year of aging, but in the opposite direction. The ΔvitE-FEV ₁ association was positive in never and current smokers (9.7 and 11.0 mL/year attenuated FEV ₁ decline, respectively), but there was little to no association in former smokers. Greater ΔvitE was associated with lower baseline α-tocopherol, higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (vs. African ancestry) (all PCYP4F2 (rs2108622-T) (2.4 µmol/L greater ΔvitE; P =0.0032). Conclusions: Greater response to vitE supplementation was associated with attenuated FEV ₁ decline, and this response was differed by rs2108622 such that individuals with the C allele may need a higher vitE intake dose to reach the same plasma level, compared to the T allele.

Objectives To investigate causality of the association of serum vitamin D with the risk and severity of COVID-19 infection. Design Two-sample Mendelian randomisation study. Setting Summary data from genome-wide analyses in the population-based UK Biobank and SUNLIGHT Consortium, applied to meta-analysed results of genome-wide analyses in the COVID-19 Host Genetics Initiative. Participants 17 965 COVID-19 cases including 11 085 laboratory or physician-confirmed cases, 7885 hospitalised cases and 4336 severe respiratory cases, and 1 370 547 controls, primarily of European ancestry. Exposures Genetically predicted variation in serum vitamin D status, instrumented by genome-wide significant single nucleotide polymorphisms (SNPs) associated with serum vitamin D or risk of vitamin D deficiency/insufficiency. Main outcome measures Susceptibility to and severity of COVID-19 infection, including severe respiratory infection and hospitalisation. Results Mendelian randomisation analysis, sufficiently powered to detect effects comparable to those seen in observational studies, provided little to no evidence for an effect of genetically predicted serum vitamin D on susceptibility to or severity of COVID-19 infection. Using SNPs in loci related to vitamin D metabolism as genetic instruments for serum vitamin D concentrations, the OR per SD higher serum vitamin D was 1.04 (95% CI 0.92 to 1.18) for any COVID-19 infection versus population controls, 1.05 (0.84 to 1.31) for hospitalised COVID-19 versus population controls, 0.96 (0.64 to 1.43) for severe respiratory COVID-19 versus population controls, 1.15 (0.99 to 1.35) for COVID-19 positive versus COVID-19 negative and 1.44 (0.75 to 2.78) for hospitalised COVID-19 versus non-hospitalised COVID-19. Results were similar in analyses using SNPs with genome-wide significant associations with serum vitamin D (ie, including SNPs in loci with no known relationship to vitamin D metabolism) and in analyses using SNPs with genome-wide significant associations with risk of vitamin D deficiency or insufficiency. Conclusions These findings suggest that genetically predicted differences in long-term vitamin D nutritional status do not causally affect susceptibility to and severity of COVID-19 infection, and that associations observed in previous studies may have been driven by confounding. These results do not exclude the possibility of low-magnitude causal effects or causal effects of acute responses to therapeutic doses of vitamin D.

Objectives To investigate causality of the association of serum vitamin D with the risk and severity of COVID-19 infection. Design Two-sample Mendelian randomization study. Setting Summary data from genome-wide analyses in the population-based UK Biobank and SUNLIGHT Consortium, applied to meta-analyzed results of genome-wide analyses in the COVID-19 Host Genetics Initiative. Participants 17,965 COVID-19 cases including 11,085 laboratory or physician confirmed cases, 7,885 hospitalized cases, and 4,336 severe respiratory cases, and 1,370,547 controls, primarily of European ancestry. Exposures Genetically predicted variation in serum vitamin D status, based on genome-wide significant single nucleotide polymorphisms (SNPs) associated with serum vitamin D or risk of vitamin D deficiency/insufficiency. Main outcome measures Susceptibility to and severity of COVID-19 infection, including severe respiratory infection and hospitalization. Results Mendelian randomization analysis, powered to detect moderate effects comparable to those seen in observational studies, provided little to no evidence for an effect of genetically predicted serum vitamin D on susceptibility to or severity of COVID-19 infection. Using SNPs in loci related to vitamin D metabolism as proxies for serum vitamin D concentration, the odds ratio for a standard deviation increase in serum vitamin D was 1.04 (95% confidence interval 0.92 to 1.18) for any COVID-19 infection versus population controls, 1.05 (0.84-1.31) for hospitalized COVID-19 versus population controls, 0.96 (0.64 to 1.43) for severe respiratory COVID-19 versus population controls, 1.15 (0.99 to 1.35) for COVID-19 positive versus COVID-19 negative, and 1.44 (0.75 to 2.78) for hospitalized COVID-19 versus non-hospitalized COVID-19. Results were similar in analyses that used all SNPs with genome-wide significant associations with serum vitamin D (i.e., including SNPs in loci with no known relationship to vitamin D metabolism) and in analyses using SNPs with genome-wide significant associations with risk of vitamin D deficiency or insufficiency. Conclusions These findings suggest that genetically predicted differences in long-term vitamin D nutritional status do not causally affect susceptibility to and severity of COVID-19 infection, and that associations observed in previous studies may have been driven by confounding. These results do not exclude the possibility of low-magnitude causal effects, nor do they preclude potential causal effects of acute responses to therapeutic doses of vitamin D. Future directions include extension of this work to non-European ancestry populations, and high-risk populations, for example persons with comorbid disease.

Dietary choline is a precursor of trimethylamine N-oxide (TMAO), a metabolite that has been associated with an increased risk of cardiovascular disease. The mechanism underlying this association is unknown, but may include TMAO effects on blood pressure (BP). This study assessed the association of choline intake with hypertension and BP in US adults through the use of NHANES 2007-2010 data. This cross-sectional study was conducted in nonpregnant individuals aged ≥20 y. Choline intake was assessed with the use of two 24-h recalls. Outcomes were BP and hypertension status, which was assessed through the use of questionnaires and BP measurements. Modifying factors (e.g., sex, race/ethnicity) and dietary compared with supplemental sources of choline intake were also investigated. The associations of total (dietary + supplemental) and dietary choline intake with the prevalence odds of hypertension differed by sex (n = 9227; P-interaction = 0.04 and 0.03, respectively). In women, both total and dietary choline intake tended to be inversely associated with hypertension (n = 4748; prevalence OR per 100 mg of choline intake: 0.89; 95% CI: 0.77, 1.02; P < 0.10 for both total and dietary choline). No association was observed in men (n = 4479; P = 0.54 and 0.49 for total choline and dietary choline, respectively). Use of choline supplements was inversely associated with hypertension in both sexes (user compared with nonuser; OR: 0.68; 95% CI: 0.49, 0.92; P = 0.01). There was little to no association of total, dietary, or supplemental choline intake with systolic or diastolic BP (n = 6,554; the mean ± SEM change in BP associated with a 100-mg difference in total choline was -0.26 ± 0.22 mm Hg for systolic BP and -0.29 ± 0.19 mm Hg for diastolic BP). Cross-sectional NHANES data do not support the hypothesis of a positive association between choline intake and BP.