Inorganic pyrophosphate is reduced in patients with systemic sclerosis.

OBJECTIVE: The pathogenesis of calcinosis cutis, a disabling complication of SSc, is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis. METHODS: Subjects with SSc and age-matched controls without SSc were recruited from the outpatient rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5' phosphosulfate. RESULTS: Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: P = 0.003; Hungarian: P < 0.001). CONCLUSIONS: Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.

A Low-Sodium DASH Dietary Pattern Affects Serum Markers of Inflammation and Mineral Metabolism in Adults with Elevated Blood Pressure.

BACKGROUND: The blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and reduced sodium intake are well established. The effects on other biomarkers related to vascular health are of interest and might assist in explaining the effects of the DASH diet and sodium reduction. OBJECTIVES: We hypothesized that a low-sodium DASH diet improves (lowers) biomarkers of inflammation [C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR)] and mineral metabolism [phosphorus and fibroblast growth factor-23 (FGF23)]. METHODS: We conducted a secondary analysis of the DASH-Sodium trial using frozen serum samples. This controlled feeding study randomly assigned 412 adults (≥22 y) with elevated blood pressure (120-159/80-95 mmHg) to consume either a DASH diet or control diet. Within each arm, participants received 3 sodium levels [low (1150 mg), intermediate (2300 mg), high (3450 mg)] in random sequence, each for 30 d. To maximize contrast, samples collected at the end of the low-sodium DASH (n = 198) and high-sodium control (n = 194) diets were compared. Between-diet differences in serum CRP, suPAR, phosphorus, and FGF23 concentrations were assessed using linear regression adjusted for age, sex, race, income, education, smoking status, and BMI. RESULTS: CRP concentrations did not differ between groups (P = 0.83), but suPAR was higher after the low-sodium DASH diet than the high-sodium control [geometric mean 2470 pg/mL (95% CI: 2380, 2560 pg/mL), compared with 2290 pg/mL (95% CI: 2210, 2380 pg/mL); P = 0.006]. Phosphorus was higher after the low-sodium DASH diet [geometric mean 3.50 mg/dL (95% CI: 3.43, 3.57 mg/dL)] compared with the high-sodium control diet [geometric mean 3.39 mg/dL (95% CI: 3.33, 3.46 mg/dL); P = 0.04]. FGF23 was also higher after the low-sodium DASH diet [geometric mean 35.3 pg/mL (95% CI: 33.3, 37.3 pg/mL) compared with 28.2 pg/mL (95% CI: 26.6, 29.8 pg/mL); P < 0.001]. CONCLUSIONS: Contrary to our hypothesis, biomarkers of inflammation and mineral metabolism were increased or unchanged by a low-sodium DASH diet compared with a high-sodium control diet in adults with elevated blood pressure.

The Percentage of Dietary Phosphorus Excreted in the Urine Varies by Dietary Pattern in a Randomized Feeding Study in Adults.

BACKGROUND: Urinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors. OBJECTIVE: We assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial. METHODS: DASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test. RESULTS: At the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P = 0.74 control vs. FV, P < 0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). CONCLUSIONS: These findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054.

Food security and diet quality, not vitamin D status are significantly associated with depression: Results from NHANES 2015-2018.

BACKGROUND: Observational research has suggested a link between vitamin D insufficiency and depression, while evidence from randomized trials examining the association have yielded inconsistent results. Food security and diet quality are also associated with both vitamin D insufficiency and depression. However, the potential interactions between these factors have not been well described. METHODS: In order to examine the associations between depression, vitamin D status, food security, and diet quality, data from 8988 US adults (≥20 years) in NHANES (National Health and Nutrition Examination Surveys) 2015-2018 were analyzed. Questionnaire-assessed depression, food security, and diet quality and laboratory-analyzed serum vitamin D were used. RESULTS: Lack of full food security and a 10-point decrease in Healthy Eating Index 2015 score were independently associated with higher risk of mild to severe depression (OR 3.72 and 1.20, respectively, p < 0.001). The association between insufficient serum vitamin D (<75 nmol/L) and depression was fully attenuated after adjusting for food security and diet quality (p = 0.41). LIMITATIONS: A major limitation of this paper, like all analyses of NHANES, is the inability to establish the temporality of the relationships between food security and diet quality with depression. CONCLUSIONS: Food security and diet quality, but not vitamin D status, were significantly associated with depression. This highlights how evaluating food security and diet quality are critical in research and public health interventions related to depression. Future interventions, especially into vitamin D insufficiency, as well as health policies should assess and address these factors.

Secular Trends in Risk Profiles Among Adults With Cardiovascular Disease in the United States.

BACKGROUND: Documenting trends in risk factors among individuals with cardiovascular disease (CVD) may inform policy and secondary prevention initiatives. OBJECTIVES: This study aimed to examine 20-year trends in risk profiles among U.S. adults with CVD and any racial/ethnic disparities. METHODS: In this serial cross-sectional analysis of 6,335 adults with self-reported CVD participating in the National Health and Nutrition Examination Survey from 1999 through 2018, we calculated age- and sex-adjusted proportions with ideal risk factor attainment. RESULTS: The proportions with ideal hemoglobin A1c (<7% if diabetes or <5.7% if not) and body mass index (<25 kg/m2) worsened from 58.7% (95% CI: 55.2%-62.1%) to 52.4% (95% CI: 48.2%-56.6%) and 23.9% (95% CI: 21.5%-26.4%) to 18.2% (95% CI: 15.6%-21.2%) from 1999-2002 to 2015-2018, respectively. After initial improvement, the proportion with blood pressure <130/80 mm Hg declined from 52.1% (95% CI: 48.9%-55.4%) in 2007-2010 to 48.6% (95% CI: 44.2%-52.7%) in 2015-2018. The proportion with non-high-density lipoprotein cholesterol levels <100 mg/dL increased from 7.3% (95% CI: 5.6%-9.5%) in 1999-2002 to 30.3% (95% CI: 25.7%-35.5%) in 2015-2018. The proportions with ideal smoking, physical activity, and diet profiles were unchanged over time, and in 2015-2018 were 77.8% (95% CI: 73.6%-81.4%), 22.4% (95% CI: 19.3%-25.9%), and 1.3% (95% CI: 0.7%-2.6%). Worsening trends were observed in Hispanic adults for cholesterol, and in Black adults for smoking (both P < 0.05 for nonlinear and linear trends). Persistently lower ideal risk factor attainment was observed for blood pressure in Black adults and for hemoglobin A1c levels in Asian adults compared with White adults (all P < 0.05 for differences). CONCLUSIONS: Trends in cardiovascular risk factor profiles in U.S. adults with CVD were suboptimal from 1999 through 2018, with persistent racial/ethnic disparities.

The association of dietary phosphorus with blood pressure: results from a secondary analysis of the PREMIER trial.

Inconsistent findings exist for the association between dietary phosphorus intake and blood pressure (BP). We examined the longitudinal association between urinary excretion and dietary intake of phosphorus (total, plant, animal, and added) with BP. This is a secondary analysis of PREMIER, a randomized behavioral intervention study in adults (25-79 years) with BP, measured at 6 months, as the primary outcome. We classified total phosphorus intake from dietary recalls into plant, animal, and added phosphorus. We modeled 6-month change of phosphorus intake (from 24 h dietary recalls, N = 622) and excretion (from 24 h urine collection, N = 564) on BP, using linear regression crude and adjusted for intervention, age, race, sex, income, education, study site, and change in energy intake (kcal/day), sodium intake (mg/day), fitness (heart rate, bpm), and DASH diet index. Baseline phosphorus intake was 1154 mg/day (95% CI 1126, 1182) with 38%, 53%, and 10% from plant, animal, and added phosphorus, respectively. Total phosphorus intake was not associated with significant changes in BP. Increased urinary phosphorus excretion was associated with a significant increase in DBP [0.14 mmHg/100 mg (0.01, 0.28), adjusted]. In several analyses, phosphorus type (plant, animal, or added) significantly modified the association between phosphorus intake and BP. For example, added phosphorus (but not plant or animal) was associated with increases in SBP and DBP, 1.24 mmHg/100 mg (0.36, 2.12) and 0.83 mmHg/100 mg (0.22, 1.44), respectively, crude. These findings suggest that the type of phosphorus may modify the association between phosphorus intake and BP. Trial registration NCT00000616 (clinicaltrials.gov).

Dietary intake of adults with and without diabetes: results from NHANES 2013-2016.

INTRODUCTION: Diet is a critical aspect of the management of adults with diabetes. This paper aims to compare dietary intakes of key macronutrients and micronutrients of US adults with and without diabetes and across the spectrum of diabetes. RESEARCH DESIGN AND METHODS: We compared absolute and energy-adjusted dietary intake of major macronutrients and micronutrients among those with and without diabetes and across the spectrum of glycemic control using a 24-hour dietary recall from a cross-sectional, nationally representative sample of 9939 US adults, 20+ years old (National Health and Nutrition Examination Survey 2013-2016). Diabetes was defined as an glycohemoglobin A1c (HbA1c)≥6.5%, fasting glucose ≥126 mg/dL, serum glucose at 2 hours following a 75 g glucose load (oral glucose tolerance test) ≥200 mg/dL, any diagnosis of diabetes or use of diabetes medication (self-reported). RESULTS: Percent of calories from macronutrients was similar for those with and without diabetes (p>0.05, energy adjusted and adjusted for age, race, and sex). In both groups, sugar accounted for about 20% of calories. Those with diabetes consumed about 7% more calcium (p=0.033), about 5% more sodium (p=0.026), and had lower diet quality (Healthy Eating Index-2015, p=0.021) than those without diabetes. Among those with diabetes, those with an HbA1c>9.0% consumed about 4% less magnesium (p-analysis of variance=0.007) than those with an HbA1c<6.5%. Results were similar within strata of age, race, and sex. Macronutrient intake did not vary consistently by HbA1c level. CONCLUSIONS: In this nationally representative sample, there were no substantial or consistent differences in the dietary intake of macronutrients or micronutrients between US adults with and without diabetes. Improving the diets of those with diabetes will likely require enhanced targeted efforts to improve the dietary intake of persons with diabetes, as well as broad efforts to improve the dietary intake of the general population.

Effects of Nasal Occlusion and Oral Contact on Perception of Metallic Taste from Metal Salts.

Iron and copper salts have complex olfactory and gustatory properties including a metallic flavor component that is decreased by nasal occlusion. To examine the sensory properties of ferrous sulfate and copper sulfate, a trained descriptive panel evaluated these compounds at equal molarity and perceived equal intensity with and without nasal occlusion. Ferrous sulfate exhibited a metallic taste and metallic aftertaste and copper sulfate exhibited a more pronounced metallic aftertaste. Metallic sensations were decreased by nasal occlusion, which in the absence of any orthonasal metallic smell, implies that the sensations were retronasally perceived volatiles in the nose open condition. Ferrous sulfate showed a larger effect of nasal occlusion. A second experiment isolated ferrous sulfate solutions from oral contact via a plastic barrier. In comparison to a condition in which oral contact was allowed, intensity ratings were decreased. This result is consistent with the hypothesis that rinses with solutions of metal salts, particularly ferrous sulfate, generate volatile lipid oxidation products in the mouth that are perceived retronasally as metallic flavors.

Dietary phosphorus intake and blood pressure in adults: a systematic review of randomized trials and prospective observational studies.

BACKGROUND: Elevated blood pressure (BP) is a major cause of preventable disease in the United States and around the world. It has been postulated that phosphorus intake may affect BP, with some studies suggesting a direct and others an inverse association. OBJECTIVES: We systematically reviewed the literature on the association of dietary phosphorus with BP in adults and performed a qualitative synthesis. METHODS: We included randomized and nonrandomized behavioral intervention and feeding studies (intervention studies) and prospective observational studies that measured dietary phosphorus intake or urinary phosphorus excretion and BP. We excluded studies of supplements, children, or individuals with major medical conditions. We searched PubMed, Embase, Cochrane Trials, and clinicaltrials.gov on 1 June, 2017 and 22 August, 2018. We assessed studies' risk of bias in their assessment of phosphorus exposure and BP. RESULTS: We reviewed 4759 publications and included 14 intervention studies (2497 participants), 3 prospective observational cohorts (17,795 participants), and 2 ongoing trials. No included intervention studies were designed specifically to achieve a phosphorus contrast. Two studies found a significant positive association of dietary phosphorus with systolic BP, 4 a significant inverse association, and 8 no significant association. Four studies found a significant inverse association with diastolic BP and 10 no significant associations. Two cohorts found lower risk of incident hypertension comparing the highest with the lowest quintiles of phosphorus intake and 1 found no significant difference: HR: 0.86 (95% CI: 0.75, 0.98); HR: 0.83 (95% CI: 0.68, 1.02); and HR: 0.75 (95% CI: 0.45, 1.27), respectively. CONCLUSIONS: We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association. This trial was registered at www.crd.york.ac.uk/prospero/ as CRD42017062489.

Dietary Cholesterol Intake and Sources among U.S Adults: Results from National Health and Nutrition Examination Surveys (NHANES), 2001⁻2014.

The 2015 Dietary Guidelines for Americans recommends that individuals should minimize their dietary cholesterol intake. However, current dietary cholesterol intake and its food sources have not been well-characterized. We examined dietary cholesterol intake by age, sex, race, and food sources using 24-h dietary recall data from a nationally representative sample of 5047 adults aged 20 years or older who participated in NHANES (2013⁻2014 survey cycle). We also reported trends in cholesterol intake across the past seven NHANES surveys. Mean dietary cholesterol intake was 293 mg/day (348 mg/day for men and 242 mg/day for women) in the 2013⁻2014 survey cycle; 39% of adults had dietary cholesterol intake above 300 mg/day (46% for men and 28% for women). Meat, eggs, grain products, and milk were the highest four food sources of cholesterol, contributing to 96% of the total consumption. Both average cholesterol intake and food source varied by age, sex, and race (each p < 0.05). Mean cholesterol intake of the overall population had been relatively constant at ~290 mg/day from 2001⁻2002 to 2013⁻2014 (p-trend = 0.98). These results should inform public health efforts in implementing dietary guidelines and tailoring dietary recommendations.

A comparison of two electric taste stimulation devices.

Electrical stimulation of the tongue, commonly used in clinical evaluations of taste dysfunction, can produce a variety of sensations including reports of metallic taste. Two studies compared responses to a fabricated electrical stimulator (a 1.6 V battery, anode side exposed) and a clinical electrogustometer (Rion TR-06). Batteries placed on the anterior dorsal tongue surface produced sensations similar in intensity and quality to those produced by the clinical electrogustometer, with equal intensity on the tongue tip for the 1.6 V battery in the range of 33-56 microA from the electrogustometer. A second study examined responses on three areas of the tongue on each side. Responses declined for areas lower in fungiform papillae for both devices, but at different rates. Higher current levels were required to match the battery in lower density areas, indicating spatial summation for the larger battery surface area. A consistent pattern of lateral differences was seen in only one subject. Quality descriptions were similar in frequency whether or not a word list was provided, with metallic, sour, pain and bitter being the most frequently mentioned words for both electric stimuli. Similarities in response to the battery device and electrogustometer were evident in intensity, qualities evoked, lack of a laterality effect and decreasing response in areas with lower fungiform papillae density. The battery device may provide an inexpensive portable alternative to an electrogustometer for use in clinical testing of taste.

Reply to Itkonen and Lamberg-Allardt's Letter to the Editor Re: McClure et al. Nutrients 2017, 9, 95.

We appreciate Drs. Itkonen and Lamberg-Allardt's interest in our recent article "Dietary Sources of Phosphorus among Adults in the United States: Results from NHANES 2001-2014" [1] [...].

Dietary Sources of Phosphorus among Adults in the United States: Results from NHANES 2001-2014.

Interest in the health effects of dietary phosphorus is burgeoning, yet sources and trends in phosphorus consumption have not been well characterized. We describe trends in and primary sources of dietary phosphorus in a nationally representative sample of 34,741 US adults, 20+ years old (NHANES 2001-2014). Dietary sources of phosphorus were estimated in nine food groups and 26 food categories. Phosphorus consumption was expressed in absolute intake, phosphorus density, and proportion contributed by dietary sources. Between 2001 and 2014, dietary phosphorus intake increased from 1345 to 1399 mg/day (p-trend = 0.02), while calorie intake slightly declined (p-trend = 0.1). Grains were the largest dietary phosphorus source, followed by meats, and milk products. Soft drinks accounted for just 3.3% of total dietary phosphorus. Phosphorus intake from grains increased 68 mg/day (p < 0.001), 25 mg/day from meats (p = 0.02), and decreased 75 mg/day (p < 0.001) from milk products. Dietary phosphorus intake and the phosphorus density of the diet are increasing. Grains are an important dietary phosphorus source that has increased in total consumption and phosphorus density. Further research is needed to determine if this is due to individuals' selection of grains or the composition of those available.