Antioxidant Bioavailability and Rapid Immune-Modulating Effects After Consumption of a Single Acute Dose of a High-Metabolite Yeast Immunogen: Results of a Placebo-Controlled Double-Blinded Crossover Pilot Study

Gitte S. Jensen,Kimberlee A. Redman,Kathleen F. Benson,Steve G. Carter,Marcie A. Mitzner,Stuart Reeves,Larry Robinson 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.9

The objective of this pilot study was to investigate the acute effects on circulating lymphocyte subsets, antioxidant status, and cytokine profile after consumption of EpiCor^ⓡ (EP) (Embria Health Sciences, Ankeny, IA, USA), a dried fermentate produced from Saccharomyces cerevisiae, using a placebo-controlled randomized crossover study design with 12 healthy adult human subjects. EP contains high levels of bioavailable antioxidants and strongly activates natural killer (NK) cells in vitro. EP consumption has been shown to increase erythrocyte hematocrit levels, boost mucosal immune protection, reduce cold/flu symptoms, reduce seasonal allergy symptoms and the need for rescue medication, and increase salivary secretory immunoglobulin A levels. This warranted further study on immune effects in humans. A within-subject analysis of data collected before and at 1 and 2 hours after consumption of a single dose of 500 mg of EP versus placebo was performed. A transient reduction in circulating T and NK cell numbers was observed 2 hours post-consumption, suggesting that homing and recirculation of these cells, as part of healthy immune surveillance, were supported by EP. The increased expression of activation markers on the CD^(3–) CD^56^+ NK cell population was significant for CD69 at 1 hour post-consumption (CD25, P<.07; CD69, P<.05), whereas for CD25 it was significant at 2 hours after consumption (CD25, P<.03; CD69, P<.15). A rapid increase in serum interferon-γ was observed at 1 hour post-consumption (P<.07; after removal of two outlying data sets, P<.05) and may have contributed to the effects seen on NK and T cell subsets. Significant increase in serum antioxidant protection was seen 2 hours after consumption (P<.04). Thus consumption of a single 500 mg dose of EP provides a rapid and transient effect on the trafficking and activation status of specific lymphocyte subsets, as well as increased antioxidant protection.

Natural Killer Cell Activation and Modulation of Chemokine Receptor Profile In Vitro by an Extract from the Cyanophyta Aphanizomenon flos-aquae

Gitte S. Jensen,Aaron N. Hart,Lue Ann Zaske,Kelly M. Patterson,Christian Drapeau 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.3

The present research was designed to study the effects of an extract from the edible cyanophyta Aphanizomenonflos-aquaeon human natural killer (NK) cells. We have previously shown, using a double-blind randomized placebo-con-trolled crossover design, that ingestion of 1.5 g of dried whole A. flos-aquaeresulted in a transient reduction in peripheralblood NK cells in 21 healthy human volunteers, suggesting increased NK cell homing into tissue. We have now identified anextract from A. flos-aquae(AFAe) that directly activates NK cells in vitroand modulates the chemokine receptor profile. NKcell activation was evaluated by expression of CD25 and CD69 on CD3. CD56. cells after 18 hours. Changes in CXCR3and CXCR4 chemokine receptor expression after 560 minutes were evaluated by immunostaining and flow cytometry. AFAeinduced the expression of CD69 on CD3. CD56. NK cells, induced CD25 expression on 25% of these cells, and acted insynergy with interleukin 2. NK cells enriched by RosetteSep?? (StemCell Technologies Inc., Vancouver, BC, Canada) werenot activated by AFAe, indicating that the NK activation was dependent on other cells such as monocytes. The low-molecu-lar-weight fraction . 5,000 of AFAe was responsible for the most robust NK cell activation, suggesting novel compounds dif-

Antioxidant and Anti-Inflammatory Properties of an Aqueous Cyanophyta Extract Derived from Arthrospira Platensis: Contribution to Bioactivities by the Non-Phycocyanin Aqueous Fraction

Gitte S. Jensen,Victoria L. Attridge,Joni L. Beaman,Jesse Guthrie,Axel Ehmann,Kathleen F. Benson 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.5

The goal for this work was to characterize basic biological properties of a novel Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but also containing a high level of non-PC bioactive compounds. Antioxidant properties were tested in parallel in the Folin–Ciocalteu assay (chemical antioxidant capacity) and in the cellular antioxidant protection (CAP-e) bioassay, where both the PC and the non-PC fractions contributed to the antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in the presence of PC, the inhibition of enzymatic activity of the inflammatory mediator Lipoxygenase was associated specifically with the non-PC fraction of ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using polymorphonuclear cells from healthy human donors. The inhibition of ROS formation was seen for both thePC and non-PC fractions, with ACE showing the most robust effect. The effects of PC, non-PC, and ACE on clotting and clot lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the presence of PC, non-PC, and ACE, the time for clot formation and lysis was not affected; however, the clots were significantly more robust. This effect was statistically significant ( p < .05) at doses between 125–500 μg/mL, and returned to baseline at lower doses. Both PC and the non-PC fraction contributed to the antioxidant properties and anti-inflammatory effects, without a negative impact on blood clotting in vitro. This suggests a potential benefit for the consumable ACE extract in assisting the reduction of inflammatory conditions.

Lymph-vascular space invasion (LVSI) as a strong and independent predictor for non-locoregional recurrences in endometrial cancer: a Danish Gynecological Cancer Group Study

Gitte Ørtoft,Lisa Lausten-Thomsen,Claus Høgdall,Estrid S Hansen,Margit Dueholm 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.5

Objective: To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer. Methods: This national cohort study (2005–2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates. Results: LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI. Conclusion: LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients.

Anti-Inflammatory Properties of a Dried Fermentate In Vitro and In Vivo

Gitte S. Jensen,Steve G. Carter,Stuart G. Reeves,Larry E. Robinson,Kathleen F. Benson 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.3

The aim of this study was to document anti-inflammatory properties of a dried fermentate derived from Saccharomyces cerevisiae (EpiCor® ), hereafter referred to as dried fermentate in vitro using cell-based bioassays, and in vivo using a skin irritation model in healthy humans. In vitro testing involved parallel assessment of primary human polymorphonuclear (PMN) cell formation of reactive oxygen species (ROS) and migration toward the inflammatory mediator Leukotriene B4. In vivo evaluation used a single-blind placebo-controlled design, where dermal histamine-induced inflammation was used as a model for the complex intercellular signals involved in the initiation, escalation, and resolution of the inflammatory response. Microvascular blood perfusion was evaluated using noninvasive laser Doppler probes applied to the inner forearms of 12 healthy human subjects, where parallel sites were treated with either dried fermentate or saline (placebo). Subjective scores of dermal irritation were also collected. Treatment of PMN cells in vitro resulted in reduced ROS formation and migratory activity toward Leukotriene B4. Clinical results demonstrated significantly reduced microvascular inflammatory responses to histamine-induced skin inflammation, and significantly reduced subjective scores of irritation at the inflamed sites treated with dried fermentate compared with the sites treated with placebo (P < .05). Treatment of inflammatory cells in vitro with dried fermentate resulted in reduced inflammatory responses. This was confirmed in vivo, suggesting that the dried fermentate facilitates the resolution of inflammatory responses. The effects using a topical skin model suggest that similar events may happen when the dried fermentate is introduced across mucosal membranes after consumption.

Pain Reduction and Improvement in Range of Motion After Daily Consumption of an Açai (Euterpe oleracea Mart.) Pulp–Fortified Polyphenolic-Rich Fruit and Berry Juice Blend

Gitte S. Jensen,David M. Ager,Kimberlee A. Redman,Marcie A. Mitzner,Kathleen F. Benson,Alexander G. Schauss 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.7

Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active® fruit juice, predominantly containing açai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.

Support of Joint Function, Range of Motion, and Physical Activity Levels by Consumption of a Water-Soluble Egg Membrane Hydrolyzate

Gitte S. Jensen,Miki R. Lenninger,Joni L. Beaman,Robert Taylor,Kathleen F. Benson 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.9

This study evaluated the effects of consumption of hydrolyzed water-soluble egg membrane (WSEM) on joint function in an otherwise healthy population experiencing chronic pain. A randomized, double-blind, placebo-controlled crossover study included two 4-week periods of placebo and WSEM consumption, separated by a 4-week washout period. Twenty-five study participants were randomized to either the ‘‘placebo-first’’ or ‘‘WSEM first’’ sequence in the crossover trial, and 22 participants completed the study requirements. Range of motion (ROM) was assessed using digital inclinometry for joints associated with vertical weight bearing from neck to knees and for shoulders. Pain at rest and when physically active was scored for the same anatomical areas using visual analog scales (VAS). Physical functioning was tracked using questionnaires with VAS. Consumption of WSEM was associated with improved ROM for neck, spine, hips, and knees, with ROM for the neck and right knee being significantly improved during WSEM consumption compared to placebo (P < .05). ROM improvement for the dominant shoulder was highly significant during WSEM consumption (P< .01). Physical activity levels were significantly higher after WSEM than after placebo consumption (P < .05). Many aspects of physical functioning as part of daily living improved. Subgroup analysis showed rapid improvement of lower back pain after 5 days of WSEM consumption compared to placebo consumption (P < .05) in subjects who participated in the study during the winter season. Daily consumption of 450mg WSEM was associated with improved joint function, comfort during daily activities, and increased physical activity.

Oral Intake of a Liquid High-Molecular-Weight Hyaluronan Associated with Relief of Chronic Pain and Reduced Use of Pain Medication: Results of a Randomized, Placebo-Controlled Double-Blind Pilot Study

Gitte S. Jensen,Victoria L. Attridge,Miki R. Lenninger,Kathleen F. Benson 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.1

The goal for this study was to evaluate the effects of daily oral intake of a consumable liquid fermentatecontaining high-molecular-weight hyaluronan, as well as to perform a basic evaluation of safety and tolerability. A randomized, double-blind placebo-controlled study design was used to examine the effects of oral intake of hyaluronan on chronic pain conditions. Safety assessment included a complete blood count with differential, blood chemistry and electrocardiogram. The study duration was 4 weeks, where three tablespoons (45 mL) product or placebo was ingested during the first 2 weeks, and two tablespoons (30 mL) was consumed during the last 2 weeks. Seventy-eight people between the age of 19 and 71 years enrolled, and 72 people completed the study. Statistical analysis was performed using the two-tailed independent ttest for between-group significance and using the paired t-test for within-group significance. A reduction in pain scores was seen after 2 weeks of consumption of both placebo (P < .1) and active (P < .065) product; the reduction was more pronounced in the group consuming the active test product. Using ‘‘within-subject’’ analysis, a highly significant reduction in chronic pain scores was seen after 2 weeks of consumption of three tablespoons of active product (P < .001), whereas only a mild nonsignificant reduction in pain scores was seen in the placebo group. During the reduced intake for the last 2 weeks of study participation, pain scores showed a slight increase. During the last 2 weeks, a significant increase in the quality of sleep (P < .005) and level of physical energy (P < .05) was seen. The pain reduction during the initial 2 weeks was associated with significant reduction in the use of pain medication (P < .05). Consumption of an oral liquid formula containing highmolecular-weight hyaluronan was associated with relief of chronic pain.

Survival and recurrence in stage II endometrial cancers in relation to uterine risk stratification after introduction of lymph node resection and omission of postoperative radiotherapy: a Danish Gynecological Cancer Group Study

Gitte Ørtoft,Claus Høgdall,Estrid S Hansen,Margit Dueholm 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.2

Objective: To evaluate survival and recurrence in stage II endometrial cancer in relation to uterine risk stratification. Outcome for stage II was compared before and after the introduction of lymph node (LN) resection and omission of all postoperative radiotherapy. Methods: The cohort consisted of 4,380 endometrial carcinoma patients radically operated (no visual tumor, all distant metastasis removed) (2005–2012) including 461 stage II. Adjusted Cox regression was used to compare survival and actuarial recurrence rates. Results: Uterine risk factors (low-, intermediate-, and high-) were the strongest predictors of survival and recurrence in stage II. Stage II low-risk having a prognosis comparable to low-risk stage I (grade 1–2, <50% myometrial invasion), whereas cervical invasion significantly increased the risk of recurrence and decreased cancer-specific survival in intermediate- and high-risk compared to the corresponding stage I risk groups. In 355 cases of 708 with cervical stromal invasion, LN-resection showed 27.9% with LN metastasis and upstaged 18.1% from stage II to IIIC resulting in longer survival and lower recurrence in LN-resected compared to non-LN resected stage II. Radical as compared to simple hysterectomy did not alter survival. Treatment with external beam radiotherapy decreased local recurrence without affecting survival. Conclusion: Uterine risk groups are the strongest predictors for survival and recurrence in stage II patients and should be considered when advising adjuvant therapy. LN-resected stage II had increased survival and decreased recurrence. Omitting radiotherapy increase vaginal recurrence without affecting survival.

Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract from Arthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation

Gitte S. Jensen,Cassandra Drapeau,Miki Lenninger,Kathleen F. Benson 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.7

The goal for this study was to evaluate safety regarding anticoagulant activity and platelet activation during daily consumption of an aqueous cyanophyta extract (ACE), containing a high dose of phycocyanin. Using a randomized, double-blind, placebo-controlled study design, 24 men and women were enrolled after informed consent, and consumed either ACE (2.3 g/day) or placebo daily for 2 weeks. The ACE dose was equivalent to ∼1 g phycocyanin per day, chosen based on the highest dose Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. Consuming ACE did not alter markers for platelet activation (P-selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen; the difference in AST levels between the two groups was significant at 2 weeks (P < .02). Reduced levels of alanine transaminase (ALT) were also seen in the group consuming ACE (P < .08). Previous studies showed reduction of chronic pain when consuming 1 g ACE per day. The higher dose of 2.3 g/day in this study was associated with significant reduction of chronic pain at rest and when physically active (P < .05). Consumption of ACE showed safety regarding markers pertaining to anticoagulant activity and platelet activation status, in conjunction with rapid and robust relief of chronic pain. Reduction in AST and ALT suggested improvement in liver function and metabolism.