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Effect of cinnamon spice on continuously monitored glycemic response in adults with prediabetes: a 4-week randomized controlled crossover trial.
Zelicha, H, Yang, J, Henning, SM, Huang, J, Lee, RP, Thames, G, Livingston, EH, Heber, D, Li, Z
The American journal of clinical nutrition. 2024;(3):649-657
Abstract
BACKGROUND Previous clinical studies showing that cinnamon spice lowers blood glucose concentrations had inconsistent results. OBJECTIVES To determine the effect of daily cinnamon spice supplementation in an amount commonly used for seasoning on glucose concentrations in adults with obesity and prediabetes. METHODS Following a 2-wk run-in period of maintaining a low polyphenol/fiber diet, 18 participants with obesity and prediabetes underwent a 10-wk randomized, controlled, double-blind, crossover trial (mean age 51.1 y; mean fasting plasma glucose 102.9 mg/dL). The participants were randomly assigned to take cinnamon (4 g/d) or placebo for 4-wk, followed by a 2-wk washout period, and then crossed over to the other intervention for an additional 4-wk. Glucose changes were measured with continuous glucose monitoring. Oral glucose tolerance testing immediately following ingestion of cinnamon or placebo was performed at 4-time points to assess their acute effects both at the baseline and end of each intervention phase. Digestive symptom logs were obtained daily. RESULTS There were 694 follow-up days with 66,624 glucose observations. When compared with placebo, 24-h glucose concentrations were significantly lower when cinnamon was administered [mixed-models; effect size (ES) = 0.96; 95 % confidence interval (CI): -2.9, -1.5; P < 0.001]. Similarly, the mean net-area-under-the-curve (netAUC) for glucose was significantly lower than for placebo when cinnamon was given (over 24 h; ES = -0.66; 95 % CI: 2501.7, 5412.1, P = 0.01). Cinnamon supplementation resulted in lower glucose peaks compared with placebo (Δpeak 9.56 ± 9.1 mg/dL compared with 11.73 ± 8.0 mg/dL; ES = -0.57; 95 % CI: 0.8, 3.7, P = 0.027). Glucose-dependent-insulinotropic-polypeptide concentrations increased during oral glucose tolerance testing + cinnamon testing (mixed-models; ES = 0.51; 95 % CI: 1.56, 100.1, P = 0.04), whereas triglyceride concentrations decreased (mixed-models; ES = 0.55; 95 % CI: -16.0, -1.6, P = 0.02). Treatment adherence was excellent in both groups (cinnamon: 97.6 ± 3.4 % compared with placebo: 97.9 ± 3.7 %; ES = -0.15; 95 % CI: -1.8, 0.2, P = 0.5). No differences were found in digestive symptoms (abdominal pain, borborygmi, bloating, excess flatus, and stools/day) between cinnamon and placebo groups. CONCLUSIONS Cinnamon, a widely available and low-cost supplement, may contribute to better glucose control when added to the diet in people who have obesity-related prediabetes. This trial was registered at clinicaltrials.gov as NCT04342624.
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California strawberry consumption increased the abundance of gut microorganisms related to lean body weight, health and longevity in healthy subjects.
Ezzat-Zadeh, Z, Henning, SM, Yang, J, Woo, SL, Lee, RP, Huang, J, Thames, G, Gilbuena, I, Tseng, CH, Heber, D, et al
Nutrition research (New York, N.Y.). 2021;:60-70
Abstract
It was our hypothesis that foods high in polyphenols and fiber have prebiotic activity. This human intervention study aimed to determine if daily consumption of freeze-dried California strawberry powder (SBP) leads to changes in the intestinal microbiota, fecal cholesterol and bile acid (BA) microbial metabolites. Fifteen healthy adults consumed a beige diet+26 g of SBP for 4 weeks, followed by 2 weeks of beige diet only. Stool samples were collected at 0, 4, and 6 weeks. Fecal microbiota was analyzed by 16S rRNA sequencing; fecal cholesterol, BA, and microbial metabolites by gas chromatography. Confirming compliance, urine concentration of pelargonidin, urolithin A glucuronide and dimethylellagic acid glucuronide were present after 4 weeks of SBP consumption. Daily SBP altered the abundance of 24 operational taxonomic units (OTUs). Comparing week 4 to baseline the most significant increases were observed for one OTU from Firmicutes\Clostridia\ Christensenellaceae\NA, one OTU from Firmicutes\ Clostridia\Mogibacteriacea\NA, one OTU from Verrucomicrobia\ Verrucomicrobiaceae\Akkermansia\Muciniphila, one OTU from Actinobacteria\ Bifidobacteriaceae\Bifidobacterium\NA, and one OTU from Bacteroidetes\Bacteroidia\ Bacteroidaceae\Bacteroides and decrease of one OTU from Proteobacteria\ Betaproteobacteria\Alcaligenaceae\Sutterella. Comparing week 4 to 6, we observed a reversal of the same OTUs from C Christensenellaceae, V muciniphilia and C Mogibacteriaceae. Fecal short chain fatty acids and most of the fecal markers including cholesterol, coprostanol, primary and secondary BAs were not changed significantly except for lithocholic acid, which was increased significantly at week 6 compared to baseline. In summary, SBP consumption increased the abundance of gut microorganisms related to lean body weight, health and longevity, and increased fecal lithocholic acid at week 6 in healthy study participants.
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Biomarkers for Atrial Fibrillation Detection After Stroke: Systematic Review and Meta-analysis.
Cameron, A, Cheng, HK, Lee, RP, Doherty, D, Hall, M, Khashayar, P, Lip, GYH, Quinn, T, Abdul-Rahim, A, Dawson, J
Neurology. 2021;(18):e1775-e1789
Abstract
BACKGROUND AND OBJECTIVE To identify clinical, ECG, and blood-based biomarkers associated with atrial fibrillation (AF) detection after ischaemic stroke or TIA that could help inform patient selection for cardiac monitoring. METHODS We performed a systematic review and meta-analysis and searched electronic databases for cohort studies from January 15, 2000, to January 15, 2020. The outcome was AF ≥30 seconds within 1 year after ischemic stroke/TIA. We used random effects models to create summary estimates of risk. Risk of bias was assessed using the Quality in Prognostic Studies tool. RESULTS We identified 8,503 studies, selected 34 studies, and assessed 69 variables (42 clinical, 20 ECG, and 7 blood-based biomarkers). The studies included 11,569 participants and AF was detected in 1,478 (12.8%). Overall, risk of bias was moderate. Variables associated with increased likelihood of AF detection are older age (odds ratio [OR] 3.26, 95% confidence interval [CI] 2.35-4.54), female sex (OR 1.47, 95% CI 1.23-1.77), a history of heart failure (OR 2.56, 95% CI 1.87-3.49), hypertension (OR 1.42, 95% CI 1.15-1.75) or ischemic heart disease (OR 1.80, 95% CI 1.34-2.42), higher modified Rankin Scale (OR 6.13, 95% CI 2.93-12.84) or National Institutes of Health Stroke Scale score (OR 2.50, 95% CI 1.64-3.81), no significant carotid/intracranial artery stenosis (OR 3.23, 95% CI 1.14-9.11), no tobacco use (OR 1.93, 95% CI 1.48-2.51), statin therapy (OR 2.07, 95% CI 1.14-3.73), stroke as index diagnosis (OR 1.59, 95% CI 1.17-2.18), systolic blood pressure (OR 1.61, 95% CI 1.16-2.22), IV thrombolysis treatment (OR 2.40, 95% CI 1.83-3.16), atrioventricular block (OR 2.12, 95% CI 1.08-4.17), left ventricular hypertrophy (OR 2.21, 95% CI 1.03-4.74), premature atrial contraction (OR 3.90, 95% CI 1.74-8.74), maximum P-wave duration (OR 3.19, 95% CI 1.40-7.25), PR interval (OR 2.32, 95% CI 1.11-4.83), P-wave dispersion (OR 7.79, 95% CI 4.16-14.61), P-wave index (OR 3.44, 95% CI 1.87-6.32), QTc interval (OR 3.68, 95% CI 1.63-8.28), brain natriuretic peptide (OR 13.73, 95% CI 3.31-57.07), and high-density lipoprotein cholesterol (OR 1.49, 95% CI 1.17-1.88) concentrations. Variables associated with reduced likelihood are minimum P-wave duration (OR 0.53, 95% CI 0.29-0.98), low-density lipoprotein cholesterol (OR 0.73, 95% CI 0.57-0.93), and triglyceride (OR 0.51, 95% CI 0.41-0.64) concentrations. DISCUSSION We identified multimodal biomarkers that could help guide patient selection for cardiac monitoring after ischaemic stroke/TIA. Their prognostic utility should be prospectively assessed with AF detection and recurrent stroke as outcomes.
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The Effect of Broccoli Sprout Extract on Seasonal Grass Pollen-Induced Allergic Rhinitis.
Yusin, J, Wang, V, Henning, SM, Yang, J, Tseng, CH, Thames, G, Arnold, I, Heber, D, Lee, RP, Sanavio, L, et al
Nutrients. 2021;(4)
Abstract
Patients exposed to pollutants are more likely to suffer from allergic rhinitis and may benefit from antioxidant treatment. Our study determined if patients diagnosed with grass-induced allergic rhinitis could benefit from broccoli sprout extract (BSE) supplementation. In total, 47 patients were confirmed with grass-induced allergic rhinitis and randomized to one of four groups: group 1 (nasal steroid spray + BSE), group 2 (nasal steroid spray + placebo tablet), group 3 (saline nasal spray + BSE) and group 4 (saline nasal spray + placebo tablet). Peak Nasal Inspiratory Flow (PNIF), Total Nasal Symptoms Scores (TNSS) and nasal mucus cytokine levels were analyzed in samples collected before and after the 3-week intervention. Comparing before and after the intervention, PNIF improved significantly when comparing Groups 1 and 2, vs. placebo, at various time points (p ≤ 0.05 at 5, 15, 60 and 240 min) following nasal challenge, while TNSS was only statistically significant at 5 (p = 0.03), 15 (p = 0.057) and 30 (p = 0.05) minutes. There were no statistically significant differences in various cytokine markers before and after the intervention. Combining nasal corticosteroid with BSE led to the most significant improvement in objective measures.
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Dual Myelomeningoceles in Twins: Case Report, Review, and Insights for Etiology.
Kobets, A, Lee, RP, Oriko, D, Jackson, E, Robinson, S, Cohen, A, Groves, ML
Pediatric neurosurgery. 2020;(6):363-373
Abstract
INTRODUCTION Despite folate supplementation, neural tube defects (NTDs) still occur in 0.5-1.0/1,000 pregnancies, with 30-50% not preventable with folate. Twinning has increased due to artificial fertilization and in itself predisposes to NTDs at a rate of 1.6/1,000. The contributions of genetic and environmental factors to myelomeningocele development remain poorly understood. Expression patterns of congenital pathologies in twins can sometimes provide etiological insight. Concordance of NTDs in twins is 0.03/1,000, with dual myelomeningocele reported in only 23 pairs, only one of which survived. We present the 24th pair, the 1st to maintain lower extremity motor function. We review all prior cases and discuss implications of twin concordance on the interplay of genetic and environmental influences. Case Report and Review: A new case of female monozygotic twins born to a well-nourished 24-year-old female is reported with details of perioperative care. Prenatal ultrasound showed L3-S4 and L5-S4 myelomeningoceles, Chiari II malformations, and ventriculomegaly. Copy number microarray was unrevealing. Each underwent uncomplicated repair on day of life 1, and ventriculoperitoneal shunt placement on days of life 10 and 16. Both had movement in the legs upon 6-week follow-up. All prior reported cases of concordant twin myelomeningoceles were abstracted and analyzed, revealing persistence of occurrence despite folate supplementation and a majority occurring in dizygotic pairs. The literature is also reviewed to summarize current knowledge of myelomeningocele pathophysiology as it relates to genetic and environmental influences. DISCUSSION Meticulous surgical and perioperative care allowed for early positive outcomes in each twin. However, etiopathogenesis remains elusive. In general, only of a minority of cases have underlying genetic lesions or clear environmental triggers. Concordance in monozygotic twins argues for a strong genetic influence; yet, literature review reveals a higher rate of concordant dizygotic twins. This, along with the observation of differing resultant phenotypes in monozygotic twins as seen in this case, prompts further investigation into nonfolate environmental influences. While efforts in genetic investigation should continue, the role of teratogens and exposures should not be minimized in research efforts, public health, and family counseling. Clinical genetic testing remains of limited utility in the majority of patients until more is known.
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Effects of branched-chain amino acids on glucose metabolism in obese, prediabetic men and women: a randomized, crossover study.
Woo, SL, Yang, J, Hsu, M, Yang, A, Zhang, L, Lee, RP, Gilbuena, I, Thames, G, Huang, J, Rasmussen, A, et al
The American journal of clinical nutrition. 2019;(6):1569-1577
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Abstract
BACKGROUND Recent studies have shown that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individuals. However, it is not known if supplementation of additional BCAAs will further impair glucose metabolism. OBJECTIVES The aim of this pilot study was to determine the effects of BCAA supplementation on glucose metabolism in obese, prediabetic individuals. METHODS This is a randomized crossover study involving 12 obese individuals with prediabetes. Participants were randomly assigned to receive a daily supplement containing either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washout in between. At each visit, an oral-glucose-tolerance test (OGTT) was performed. Collected blood samples were used to measure glucose, insulin, and insulin resistance-associated biomarkers. RESULTS BCAA supplementation tended to decrease the plasma glucose area under the curve (AUC) measured by the OGTT (AUC percentage change from supplementation baseline, BCAA -3.3% ± 3%; low-BCAA: 10.0% ± 6%; P = 0.08). However, BCAA supplementation did not affect plasma insulin during OGTT challenge (BCAA: -3.9% ± 8%; low-BCAA: 14.8% ± 10%; P = 0.28). The plasma concentrations of nerve growth factor (BCAA: 4.0 ± 1 pg/mL; low-BCAA: 5.7 ± 1 pg/mL; P = 0.01) and monocyte chemoattractant protein-1 (BCAA: -0.4% ± 9%; low-BCAA: 29.0% ± 18%; P = 0.02) were significantly lowered by BCAA supplementation compared to low-BCAA control. Plasma interleukin 1β was significantly elevated by BCAA supplementation (BCAA: 231.4% ± 187%; low-BCAA: 20.6% ± 33%; P = 0.05). BCAA supplementation did not affect the circulating concentrations of the BCAAs leucine (BCAA: 9.0% ± 12%; low-BCAA: 9.2% ± 11%), valine (BCAA: 9.1% ± 11%; low-BCAA: 12.0% ± 13%), or isoleucine (BCAA: 2.5% ± 11%; low-BCAA: 7.3% ± 11%). CONCLUSIONS Our data suggest that BCAA supplementation did not impair glucose metabolism in obese, prediabetic subjects. Further studies are needed to confirm the results seen in the present study. This study was registered at clinicaltrials.gov as NCT03715010.
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Bioavailability and bioactivity of free ellagic acid compared to pomegranate juice.
Long, J, Guo, Y, Yang, J, Henning, SM, Lee, RP, Rasmussen, A, Zhang, L, Lu, QY, Heber, D, Li, Z
Food & function. 2019;(10):6582-6588
Abstract
Pomegranates are an excellent source of ellagic acid (EA), ellagitannins (ETs), anthocyanins and other phytochemicals. The health benefits of pomegranate (Pom) have been mainly related to its EA and ET content. The objective of the present study was to determine EA bioavailability and bioactivity from different sources such as pure/free or natural form (PomJ). This was a cross-over study with healthy volunteers consuming one dose of EA dietary supplement (500 mg free EA) vs. one serving of PomJ (237 mL, ∼120 mg of EA) in a random order. Our data showed that there was no difference in plasma EA concentration between PomJ and EA intake; however, urinary dimethylellagic acid glucuronide (DMEAG), normalized to creatinine, was significantly higher after the consumption of PomJ compared to EA. Plasma insulin at 1 h increased after PomJ consumption compared to the baseline while decreased after EA consumption compared to the baseline. Plasma glucose decreased below the baseline 2 h after the consumption of PomJ but not EA. Plasma leptin was significantly decreased at 1 and 2 h after PomJ and EA consumption. Plasma MCP1 decreased only after PomJ but not after pure EA consumption. To conclude, one serving of PomJ provided the same level of EA in blood, while the increase in phase II metabolism of EA and an acute suppression of plasma MCP1 were only observed after PomJ consumption, suggesting that other constituents present in PomJ, in addition to EA, are bioactive and likely play a role in regulating EA phase II metabolism.
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Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.
Li, Z, Henning, SM, Lee, RP, Lu, QY, Summanen, PH, Thames, G, Corbett, K, Downes, J, Tseng, CH, Finegold, SM, et al
Food & function. 2015;(8):2487-95
Abstract
The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.
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Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer.
Henning, SM, Wang, P, Abgaryan, N, Vicinanza, R, de Oliveira, DM, Zhang, Y, Lee, RP, Carpenter, CL, Aronson, WJ, Heber, D
Molecular nutrition & food research. 2013;(3):483-93
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SCOPE Tea polyphenols are metabolized by the colonic microflora yielding phenolic metabolites, which may contribute to the health benefits of tea. We determined the serum and urine concentrations of phenolic acids, hippuric acid, and polyhydroxyphenyl-γ-valerolactones during green tea (GT) and black tea (BT) administration. The effects of (-)-epigallocatechin gallate (EGCG) and 3,4-dihydroxyphenylacetic acid (3,4-DHPAA) alone and in combination on bioavailability, intracellular metabolism, and antiproliferative activity were determined in HCT-116 colon cancer cells. METHODS AND RESULTS The concentration of phenolic metabolites was quantified by HPLC with electrochemical detection and MS. Urine concentrations of 4-hydroxyphenylacetic acid (4-HPAA), 3-hydroxyphenylacetic acid (3-HPAA), and polyhydroxy-γ-valerolactones were increased significantly in men drinking GT compared to control. Urine concentration of 3-O-methylgallic acid (3OMGA) was significantly increased in men drinking BT compared to control. Serum 3,4-DHPAA was significantly increased after consumption of GT and BT and 4-HPAA after GT consumption. In vitro treatment of HCT-116 colon cancer cells with 3,4-DHPAA and EGCG exhibited an additive antiproliferative effect, while methylation of 3,4-DHPAA was significantly decreased. 3OMGA exhibited the strongest antiproliferative activity among the phenolic acids. CONCLUSION The consumption of both, GT and BT, was associated with a significant increase in urinary and serum phenolic acids.
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Green tea polyphenols and metabolites in prostatectomy tissue: implications for cancer prevention.
Wang, P, Aronson, WJ, Huang, M, Zhang, Y, Lee, RP, Heber, D, Henning, SM
Cancer prevention research (Philadelphia, Pa.). 2010;(8):985-93
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Epidemiologic, preclinical, and clinical trials suggest that green tea consumption may prevent prostate cancer through the action of green tea polyphenols including (-)-epigallocatechin-3-gallate (EGCG). To study the metabolism and bioactivity of green tea polyphenols in human prostate tissue, men with clinically localized prostate cancer consumed six cups of green tea (n = 8) daily or water (n = 9) for 3 to 6 weeks before undergoing radical prostatectomy. Using high-performance liquid chromatography, 4''-O-methyl EGCG (4''-MeEGCG) and EGCG were identified in comparable amounts, and (-)-epicatechin-3-gallate was identified in lower amounts in prostatectomy tissue from men consuming green tea (38.9 +/- 19.5, 42.1 +/- 32.4, and 17.8 +/- 10.1 pmol/g tissue, respectively). The majority of EGCG and other green tea polyphenols were not conjugated. Green tea polyphenols were not detected in prostate tissue or urine from men consuming water preoperatively. In the urine of men consuming green tea, 50% to 60% of both (-)-epigallocatechin and (-)-epicatechin were present in methylated form with 4'-O-MeEGC being the major methylated form of (-)-epigallocatechin. When incubated with EGCG, LNCaP prostate cancer cells were able to methylate EGCG to 4''-MeEGCG. The capacity of 4''-MeEGCG to inhibit proliferation and NF-kappaB activation and induce apoptosis in LNCaP cells was decreased significantly compared with EGCG. In summary, methylated and nonmethylated forms of EGCG are detectable in prostate tissue following a short-term green tea intervention, and the methylation status of EGCG may potentially modulate its preventive effect on prostate cancer, possibly based on genetic polymorphisms of catechol O-methyltransferase.