脑源性神经营养因子与老年患者术后认知功能障碍的研究进展

近年来,越来越多人关注术后认知功能障碍(POCD),但其发生机制目前仍然未能清楚阐明。探讨老年POCD发生机制与脑源性神经营养因子(BDNF)表达及其下游信号通路激活的关系是研究重点。为进一步明确老年POCD的发生机制,减少老年POCD的出现,提高老年患者生存质量,本文选择Web of Science、PubMed检索并回顾有关BDNF及POCD的文献以探讨二者的关系。     

Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial

Mild cognitive impairment (MCI) and early Alzheimer’s disease (AD) are characterized by blood–brain barrier (BBB) breakdown leading to abnormal BBB permeability ahead of brain atrophy or dementia. Previous findings in AD mouse models have reported the beneficial effect of extra-virgin olive oil (EVOO) against AD, which improved BBB and memory functions and reduced brain amyloid-β (Aβ) and related pathology. This work aimed to translate these preclinical findings to humans in individuals with MCI. We examined the effect of daily consumption of refined olive oil (ROO) and EVOO for 6 months in MCI subjects on BBB permeability (assessed by contrast-enhanced MRI), and brain function (assessed using functional-MRI) as the primary outcomes. Cognitive function and AD blood biomarkers were also assessed as the secondary outcomes. Twenty-six participants with MCI were randomized with 25 participants completed the study. EVOO significantly improved clinical dementia rating (CDR) and behavioral scores. EVOO also reduced BBB permeability and enhanced functional connectivity. While ROO consumption did not alter BBB permeability or brain connectivity, it improved CDR scores and increased functional brain activation to a memory task in cortical regions involved in perception and cognition. Moreover, EVOO and ROO significantly reduced blood Aβ₄₂/Aβ₄₀ and p-tau/t-tau ratios, suggesting that both altered the processing and clearance of Aβ. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting EVOO biophenols contributed to such an effect. This proof-of-concept study justifies further clinical trials to assess olive oil’s protective effects against AD and its potential role in preventing MCI conversion to AD and related dementias.     

电针治疗难治性抑郁症的效果及对血清BDNF浓度的影响

目的观察电针治疗难治性抑郁症的效果及对血清脑源性神经营养因子（BDNF）浓度的影响。方法将88例单用一种SSRI（选择性5-HT再摄取阻滞剂）类药物的难治性抑郁症患者,随机分成电针组和对照组：电针组在继续使用原SSRI类抗抑郁剂的基础上加用电针治疗,对照组继续使用原SSRI类抗抑郁剂至疗程结束;疗程8周。入组时及治疗后2、4、8周末进行汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）、副反应量表（TESS）评定,治疗前后采用酶联夹心免疫吸附测定（ELISA）技术进行血清BDNF浓度的测定。结果①电针组显效率48.8%,显著高于对照组显效率24.4%;②电针组出现的不良反应较对照组少;③电针组治疗后血清BDNF水平明显高于治疗前水平（P〈0.01）。结论电针治疗难治性抑郁症安全、有效,明显提高血清BDNF水平。     

The Effect of Omega-3 Fatty Acids on Thromboxane,Brain-Derived Neurotrophic Factor,Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child’s Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).     

The Effects of Mold-Fermented Cheese on Brain-Derived Neurotrophic Factor in Community-Dwelling Older Japanese Women With Mild Cognitive Impairment: A Randomized,Controlled, Crossover Trial

ObjectivesTo investigate the effects of mold-fermented cheese (MFC) on brain-derived neurotrophic factor (BDNF) in community-dwelling older Japanese women with mild cognitive impairment (MCI).DesignRandomized controlled crossover trial.InterventionParticipants were randomly assigned to 2 groups. The MFC group was provided with 33.4 g MFC (camembert cheese) daily for 3 months, and the non-MFC group was provided with the same amount of non-MFC (processed cheese made from mozzarella cheese and cream cheese) for 3 months. After the post-intervention analysis (primary analysis), there was a 3-month washout period, followed by a crossover period (secondary analysis).Setting and ParticipantsUrban community in Tokyo, Japan. A total of 71 older women aged ≥70 years with MCI based on selected criteria in 689 community-dwelling women.MeasuresFace-to-face interviews were conducted to administer the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) and collect data on medical history. Physical function measures included grip strength, knee extension strength, and usual walking speed. Blood samples were obtained to determine the levels of albumin, vitamin D, high-sensitivity C-reactive protein, and BDNF.ResultsSignificant interactions were observed in BDNF after intervention of MFC intake in the secondary (F = 5.368, P = .024) and combined analyses (F = 4.354, P = .039) but not the primary analysis. There were no significant changes in the 3 categories of MMSE score (normal, MCI, moderate or severe cognitive impairment), GDS score, physical function, and blood indicators.Conclusions and ImplicationsThree months of MFC ingestion had beneficial effects on BDNF levels in community-dwelling older women with MCI; however, the BDNF increases did not translate into MMSE scores. Further study into the effects of interventions on cognitive function and depression in older people with MCI is necessary.     

A Randomized Controlled Trial Investigating the Effects of Parenteral Fish Oil on Survival Outcomes in Critically Ill Patients With Sepsis

Introduction: Death from sepsis in the intensive care unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with ω‐3 has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial. Method: A randomized control trial investigating the effects of parenteral ω‐3 was carried out. Consecutive patients diagnosed with sepsis were entered into the study and randomized to receive either parenteral ω‐3 or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the Sequential Organ Failure Assessment (SOFA) score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C‐reactive protein (CRP), and days free of organ dysfunction/failure. Results: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral ω‐3 were associated with a significant reduction in new organ dysfunction (Δ‐SOFA 2.2 ± 2.2 vs. 1.0 ± 1.5, P = .005 and maximum‐SOFA 10.1 ± 4.2 vs. 8.1 ± 3.2, P = .041) and maximum CRP (186.7 ± 78 vs. 141.5 ± 62.6, P = .019). There was no significant reduction in the length of stay between cohorts. Patients treated with ω‐3 in the strata of less severe sepsis had a significant reduction in mortality (P = .042). Conclusion: The treatment of critically ill septic patients with parenteral ω‐3 is safe. It is associated with a significant reduction in organ dysfunction. It may be associated with a reduction in mortality in patients with less severe sepsis.     

Daily Vinegar Ingestion Improves Depression Scores and Alters the Metabolome in Healthy Adults: A Randomized Controlled Trial

Daily vinegar ingestion has been linked to improved glycemic control, but recent data suggest a separate unexplored role for vinegar in mental health. Utilizing a placebo-controlled, parallel arm study design, this 4-week trial examined the impact of daily vinegar ingestion on mood states and urinary metabolites in healthy college students. Participants were randomized to the vinegar group (VIN: n = 14; 1.5 g acetic acid/day as liquid vinegar) or the control group (CON: n = 11; 0.015 g acetic acid/day as a pill) with no change to customary diet or physical activity. At baseline and at study week four, participants completed the Profile of Mood States (POMS) and the Center for Epidemiological Studies-Depression (CES-D) questionnaires and provided a first-morning urine sample for targeted metabolomics analyses. The change in both POMS depression scores and CES-D scores differed significantly between groups favoring improved affect in the VIN versus CON participants after four weeks. Metabolomics analyses pre and post-intervention suggested metabolite alterations associated with vinegar ingestion that are consistent for improved mood, including enzymatic dysfunction in the hexosamine pathway as well as significant increases in glycine, serine, and threonine metabolism. These data warrant continued investigation of vinegar as a possible agent to improve mood state.     

Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in overweight or obese subjects: A double-blind,randomized, placebo-controlled trial

Abstract

Objective

Previous studies have shown a positive effect of zinc as an adjunctive therapy on reducing depressive symptoms. However, to our knowledge, no study has examined the effect of zinc monotherapy on mood. The aim of the present study was to determine the effects of zinc monotherapy on depressive symptoms and serum brain-derived neurotrophic factor (BDNF) levels in overweight or obese subjects.

Methods

Fifty overweight or obese subjects were randomly assigned into two groups and received either 30 mg zinc or placebo daily for 12 weeks. At baseline and post-intervention, depression severity was assessed using Beck depression inventory II (BDI II), and serum BDNF and zinc levels were determined by enzyme-linked immunosorbent assay and atomic absorption spectrophotometry, respectively.

Results

The trial was completed with 46 subjects. After a 12-week supplementation, serum zinc and BDNF levels increased significantly in the zinc-supplemented group compared with the placebo group. BDI scores declined in both the groups at the end of the study, but reduction in the zinc-supplemented group was significantly higher than the placebo group. More analysis revealed that following supplementation, BDI scores decreased in subgroup of subjects with depressive symptoms (BDI ≥ 10) (n = 30), but did not change in the subgroup of non-depressed subjects (BDI < 10) (n = 16). Moreover, a significant inverse correlation was observed between serum BDNF levels and depression severity in all participants. Interestingly, a significant positive correlation was found between serum BDNF and zinc levels at baseline.

Conclusion

Zinc monotherapy improves mood in overweight or obese subjects most likely through increasing BDNF levels.     

A Tailored Discharge Program Improves Frailty and Mood in Patients Undergoing Usual Rehabilitative Care: A Randomized Controlled Trial

ObjectiveTo investigate whether a tailored intersectoral discharge program (TIDP) impacts on multidimensional frailty, rehospitalization days, and patient-related outcome measures in older in-patients undergoing acute care and usual rehabilitative care.DesignRandomized controlled trial of TIDP vs usual rehabilitative care with a 6-month follow-up, 2019–2020, and historical control with a 6-month follow-up, 2016–2019.Setting and ParticipantsGeriatric co-managed internal medicine ward of a metropolitan university hospital. One hundred-twelve multimorbid patients older than age 60 years were consecutively assessed for eligibility and inclusion (age ≥60 years, multimorbidity, admitted for treatment of acute disease, at least 2 geriatric syndromes requiring usual rehabilitative care, and able to consent) and signed informed consent, with 110 recruited and randomized to either TIDP or usual rehabilitative care. At discharge, 104 patients were alive in the intention-to-treat group, the 6-month follow-up was completed for 91 patients. A historical control group of 468 patients was included for comparison.InterventionTIDP as intervention included contact with treating general practitioner to discuss the further treatment plan, a structured medical and lifestyle counseling to patients and caregivers at admission as well as a discharge program with internist, geriatrician, and general practitioner in shared decision making with patients.MethodsFifty-four patients underwent TIDP, 53 patients underwent usual rehabilitative care only. Rehospitalization days at follow-up as primary endpoint; multidimensional frailty and prognosis (Multidimensional Prognostic Index, Geriatric Depression Scale, Rosenberg Self-Esteem Scale, quality of life, falls, mortality, home care service need, and need of long-term care at 1-, 3- and 6-month follow-up as secondary endpoints.ResultsTIDP (median age 76.0 years, 56% female) showed significantly improved Multidimensional Prognostic Index scores at discharge compared with usual rehabilitative care (median age 78.5 years, 58% female) (0.43 vs 0.49, P = .011). Compared with usual rehabilitative care, TIDP improved self-confidence (Rosenberg Self-Esteem Scale 13.9 vs 12.4, P = .009) and mood (Geriatric Depression Scale 4 vs 5, P = .027) at follow-up. Compared with historical control (median age 77.0 years, 39 % female), usual rehabilitative care patients showed significantly lower rehospitalization rates (53% vs 70%, P = .002) and lower mortality rates (13% vs 32%, P < .001).Conclusions and ImplicationsA feasible TIDP improves frailty and mood in advanced age. In older patients undergoing potentially disabling acute treatments, usual rehabilitative care significantly reduces rehospitalization rates. Therefore, implementing geriatric treatment in general is useful to improve outcomes in older in-patients and a tailored discharge program can further increase the benefit for this frail population.     

Effect of Evening Primrose Oil Supplementation on Biochemical Parameters and Nutrition of Patients Treated with Isotretinoin for Acne Vulgaris: A Randomized Double-Blind Trial

Background: Acne vulgaris is one of the most common skin diseases. One of the therapeutic options recommended for severe acne or acne that has not responded to previous therapies is isotretinoin. However, its use may lead to adverse changes in the serum lipid profile and increased levels of transaminases. In this study, we evaluated the effect of supplementation with evening primrose oil in acne vulgaris patients treated with isotretinoin on blood lipid parameters and transaminase activity. Methods: Study participants were randomly assigned to two treatments: conventional with isotretinoin (25 patients) and novel with isotretinoin combined with evening primrose oil (4 × 510 mg/day; 25 patients) for 9 months. Results: Compared to isotretinoin treatment, isotretinoin treatment combined with evening primrose oil had a positive effect on TCH concentrations (mean: 198 vs. 161, p < 0.001), LDL (95.9 vs. 60.2, p < 0.001), HDL (51.0 vs. 48.0, p < 0.001), TG (114 vs. 95.0, p < 0.001), ALT (24.0 vs. 22.0, p < 0.001), and AST (28.0 vs. 22.0, p < 0.001), but had no effect on the energy and ingredient content of the diets (p > 0.05) after treatment. Conclusion: Evening primrose oil was found to have beneficial effects on lipid profiles and transaminase activity during isotretinoin treatment. However, longer studies are needed to make more reliable decisions regarding the use of evening primrose oil and its safety in clinical practice. The evening primrose oil treatment group also showed a reduction in dietary energy due to a reduction in dietary protein and carbohydrates.     

The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind,Randomized Controlled Trial

Objective: Previous studies have shown that the bioflavonoid quercetin has anti-inflammatory and anti-nociceptive effects. We investigated the effect of quercetin supplementation on inflammation, disease severity, and clinical symptoms in women with rheumatoid arthritis (RA).

Methods: The present study was a randomized, double-blind, placebo-controlled clinical trial in which 50 women with RA were allocated into a quercetin (500 mg/day) or placebo group for 8 weeks. Plasma levels of high-sensitivity tumor necrosis factor-α (hs-TNFα), erythrocyte sedimentation rate (ESR), clinical symptoms including early morning stiffness (EMS), morning and after-activity pain, and tender (TSC) and swollen joint counts (SJC) were determined. Disease activity and functional disability were assessed by Disease Activity Score 28 (DAS-28), physician global assessment (PGA), and a health assessment questionnaire (HAQ) at the beginning and end of the study.

Results: Quercetin supplementation for 8 weeks significantly reduced EMS, morning pain, and after-activity pain (p < 0.05). DAS-28 and HAQ scores decreased in the quercetin group compared to placebo and the number of patients with active disease significantly decreased in the quercetin group. Plasma hs-TNFα level was significantly reduced in the quercetin group compared to placebo (p < 0.05). There were no significant differences in TJC and SJC between groups but TJC significantly decreased in the quercetin group after the intervention. Supplementation had an effect on ESR but it was not significant (p > 0.05).

Conclusions: Five hundred milligrams per day quercetin supplementation for 8 weeks resulted in significant improvements in clinical symptoms, disease activity, hs-TNFα, and HAQ in women with RA.     

Whey Protein Supplementation Improves Rehabilitation Outcomes in Hospitalized Geriatric Patients: A Double Blinded,Randomized Controlled Trial

Whey protein supplementation (WPS) has been shown to improve functional outcomes in populations that are able to participate in high-intensity resistance training. The purpose of the study was to evaluate the efficacy of WPS on rehabilitation outcomes in a frail, hospitalized elderly population. Men and women (n?=?47) were randomly assigned to either a control group or WPS group for the length of their hospital stay. Several functional and serum measures were determined pre- and post-intervention. WPS significantly increased average daily protein intake and was well tolerated. The WPS group exhibited significant improvements in grip strength and knee extensor force over the control group, and a significant positive correlation was found between change in prealbumin and percent-increase knee extensor force. These findings support the use of WPS to improve protein nutritional status and rehabilitation outcomes in a clinical setting involving a frail, elderly population.     

Oral Supplement Containing Hydroxytyrosol and Punicalagin Improves Dyslipidemia in an Adult Population without Co-Adjuvant Treatment: A Randomized,Double-Blind,Controlled and Crossover Trial

Hydroxytyrosol (HT) and punicalagin (PC) exert cardioprotective and antiatherosclerotic effects. This study evaluated the effect of an oral supplement containing HT and PC (SAx) on dyslipidemia in an adult population. A randomized, double-blind, controlled, crossover trial was conducted over a 20-week period. SAx significantly reduced the plasma levels of triglycerides (TG) in subjects with hypertriglyceridemia (≥150 mg/dL) (from 200.67 ± 51.38 to 155.33 ± 42.44 mg/dL; p < 0.05), while no such effects were observed in these subjects after the placebo. SAx also significantly decreased the plasma levels of low-density lipoprotein cholesterol (LDL-C) in subjects with high plasma levels of LDL-C (≥160 mg/dL) (from 179.13 ± 16.18 to 162.93 ± 27.05 mg/dL; p < 0.01), while no such positive effect was observed with the placebo. In addition, the placebo significantly reduced the plasma levels of high-density lipoprotein cholesterol (HDL-C) in the total population (from 64.49 ± 12.65 to 62.55 ± 11.57 mg/dL; p < 0.05), while SAx significantly increased the plasma levels of HDL-C in subjects with low plasma levels of HDL-C (<50 mg/dL) (from 44.25 ± 3.99 to 48.00 ± 7.27 mg/dL; p < 0.05). In conclusion, the supplement containing HT and PC exerted antiatherosclerotic and cardio-protective effects by considerably improving dyslipidemia in an adult population, without co-adjuvant treatment or adverse effects.     

Effects of Zinc and Selenium Supplementation on Thyroid Function in Overweight and Obese Hypothyroid Female Patients: A Randomized Double-Blind Controlled Trial

Objective: Zinc (Zn) and selenium (Se) are essential trace elements involved in thyroid hormone metabolism. This study was conducted to investigate the effects of Zn and Se supplementation on thyroid function of overweight or obese female hypothyroid patients in a double-blind, randomized controlled trial.

Methods: Sixty-eight female hypothyroid patients were randomly allocated to one of the 4 supplementation groups receiving Zn + Se (ZS; 30 mg Zn as zinc-gluconate and 200 μg Se as high-selenium yeast), Zn + placebo (ZP), Se + placebo (SP), or placebo + placebo (PP) for 12 weeks. Serum Zn, Se, free and total triiodothyronine (FT3 and FT4), free and total thyroxine (FT4 and TT4), thyroid-stimulating hormone (TSH), and anthropometric parameters were measured. Dietary intake was recorded using 24-hour food recall. Physical activity questionnaire was completed.

Results: No significant alterations were found in serum Zn or Se concentrations. Mean serum FT3 increased significantly in the ZS and ZP groups (p < 0.05) but this effect was significant in the ZP group compared to those in SP or PP groups (p < 0.05). Mean serum FT4 increased and TSH decreased significantly (p < 0.05) in the ZS group. TT3 and TT4 decreased significantly in the SP group (p < 0.05). Mean FT3:FT4 ratio was augmented significantly in the ZP group (p < 0.05). No significant treatment effects were found for TT3, FT4, TT4, or TSH between groups.

Conclusion: This study showed some evidence of an effect of Zn alone or in combination with Se on thyroid function of overweight or obese female hypothyroid patients.     

A Novel Fortified Dairy Product and Sarcopenia Measures in Sarcopenic Older Adults: A Double-Blind Randomized Controlled Trial

ObjectivesTo evaluate the efficacy of daily consumption of fortified yogurt with beta-Hydroxy beta-Methyl Butyrate (HMB) and vitamins D and C on measures of sarcopenia, inflammation, and quality of life in sarcopenic older adults.DesignIn this 12-week randomized double-blind controlled trial, participants received either yogurt fortified with 3 g HMB, 1000 IU vitamin D, and 500 mg vitamin C in the intervention group (n = 33) or plain yogurt in the control group (n = 33).Setting and ParticipantsA total of 66 older adults with sarcopenia recruited from the community in Shiraz, Iran.MeasuresBody composition, muscle strength, and functionality were measured using Dual-energy-X-ray Absorptiometry (DXA), hydraulic handgrip dynamometer, and usual gait speed, respectively. Serum concentrations of vitamin D, insulin-like growth factor-1 (IGF-1), C-reactive protein (hs-CRP), malondialdehyde, and insulin were measured at baseline and after 12 weeks. Health-related quality of life (HRQoL) was also evaluated using SF-12 questionnaire.ResultsConsumption of fortified yogurt was associated with improvement in handgrip strength [mean change (95% confidence interval) 4.36 (3.35–5.37) vs. 0.97 (?0.04 to 1.99)] and gait speed [0.10 (0.07–0.13) vs. 0.01 (0.00–0.04)] in the intervention group compared with the control group (P < .001). In addition, the results revealed a significant increase in vitamin D and IGF-1 levels in the intervention group (P < .001). The nutritional intervention significantly prevented any increase in the serum concentration of hs-CRP compared with the control group (P = .033). The results also showed a more significant decrease in the malondialdehyde level in the intervention group compared with the control (P = .008). Moreover, there were significant differences between the 2 groups regarding physical aspects of HRQoL (P = .035).Conclusions and ImplicationsA novel dairy product fortified with HMB, vitamin D, and vitamin C not only could enhance muscle strength and functionality, but also modulate anabolic and inflammatory conditions as well as quality of life. This study suggested that specific nutritional interventions alone could be beneficial, especially for those who are unable to exercise.     

Denosumab Improves Bone Mineral Density in Patients With Intestinal Failure Receiving Home Parenteral Nutrition: Results From a Randomized,Controlled Clinical Trial

Aim : Low bone mineral density (BMD) is commonly reported in patients receiving home parenteral nutrition (HPN). Oral and intravenous calcium, vitamin D, and bisphosphonates have been used to treat BMD but with low efficiency due to their limited absorption and patient compliance. Denosumab is a new drug that helps prevent osteoclast development and activation and led to decreased bone resorption in some studies. The aim of this study was to assess its value in HPN patients. Methods : Between November 2011 and March 2013, 49 patients receiving HPN (29 women, 20 men, mean age 55.3 years) who met the eligibility criteria were randomly assigned to a denosumab or control group. Regional dual‐energy x‐ray absorptiometry of the spine and hip was performed before therapy and after 12 months. BMD, T score, and z score were assessed. Results : Fifteen patients received 2 doses of therapy and were fully reassessed after 1 year. At baseline and after 12 months, the absorptiometry revealed T scores of ?3.439 standard deviations (SD) vs ?2.33 SD at lumbar segment 2 (L2) and ?2.957 SD vs ?2.067 SD at lumbar segment 3 (L3), z scores of ?2.24 SD vs ?1.36 SD at L2 and ?1.995 vs ?1.067 SD at L3, and BMD of 0.801 vs 0.946 at L2 and 0.857 vs 0.979 at L3, respectively. Two serious outcomes were reported, without any correlation to the intervention. Two patients were weaned off HPN and hence discontinued. One patient experienced sciatica, resulting in discontinuation of the intervention. Conclusions : This study showed that denosumab may be a valuable treatment option for improving BMD in HPN patients.     

Effect of Concomitant Consumption of Fish Oil and Vitamin E on T Cell Mediated Function in the Elderly: A Randomized Double-Blind Trial

Objectives: To determine if concomitant consumption of fish oil and vitamin E would modify the vitamin E level needed for improving T cell mediated function in elderly.

Methods: A randomized and double-blind study was conducted using 40 healthy male and female elderly subjects (>65 y) who were randomly assigned to one of 4 groups (n = 10/group). All the subjects received 5 g of fish oil daily containing 1.5 g eicosapentaenoic acid (EPA) and 1 g docosahexaenoic acid (DHA), and a capsule containing different doses of dl-α-tocopherol (0, 100, 200 or 400 mg/day) for 3 mo. Plasma vitamin E and fatty acid levels, and in vivo [delayed-type hypersensitivity skin response (DTH) and T cell sub-population analysis] and ex vivo [mitogen-stimulated peripheral blood mononuclear cells (PBMC) proliferation and interleukin (IL)-2 production] immune functions were determined at baseline and after supplementation.

Results: The control group (fish oil only) did not show a statistically significant change in either DTH or PBMC proliferation. DTH response, however, was significantly increased from baseline in all groups supplemented with fish oil plus vitamin E and a significant positive correlation between DTH response and plasma concentrations of α-tocopherol was observed. PBMC proliferation was only significantly increased in the group supplemented with fish oil plus 200 mg vitamin E. However, the changes caused by fish oil plus vitamin E in either DTH or PBMC proliferation were not significantly different from those observed in control group. Plasma levels of α-tocopherol were significantly increased in all three fish oil plus vitamin E groups and the increase in plasma α-tocopherol level was less profound than that previously reported when vitamin E was given alone.

Conclusions: The immuno-enhancing effect of vitamin E in the elderly is dampened when it is concomitantly consumed with fish oil. This may be due to the smaller increase in plasma concentrations of vitamin E in the presence of fish oil.     

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized,Double-Blind,Placebo-Controlled Trial

Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K₁ (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA.

Materials and Methods: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K₁ or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention.

Results: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K₁ group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05).

Conclusions: Vitamin K₁ supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.     

Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized,Double-Blind,Placebo-Controlled Trial

Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (10⁸ CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8–12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.     

Reduction of Overweight and Eating Disorder Symptoms via the Internet in Adolescents: A Randomized Controlled Trial

PURPOSE: Overweight in adolescence is a significant problem which is associated with body dissatisfaction and eating disorder (ED) behaviors. Cost-effective methods for early intervention of obesity and prevention of ED are important because of the refractory nature of both. This multisite RCT evaluated an Internet-delivered program targeting weight loss and ED attitudes/behaviors in adolescents. METHODS: A total of 80 overweight adolescents 12-17 years of age completed Student Bodies 2 (SB2), a 16-week cognitive-behavioral program, or usual care (UC). RESULTS: Body mass index (BMI) z-scores were reduced in the SB2 group compared with the UC group from baseline to post-intervention (p = .027; eta(p)(2) = .08). The SB2 group maintained this reduction in BMI z-scores at 4-month follow-up, but significant differences were not observed because of improvement in the UC group. The SB2 group evidenced greater increases in dietary restraint post-intervention (p = .016) and less improvement on shape concerns at follow-up (p = .044); however these differences were not clinically significant. No other statistically significant differences were noted between groups on ED attitudes or behaviors. The SB2 participants reported using healthy eating-related and physical activity-related skills more frequently than UC participants post-intervention (p = .001) and follow-up (p = .012). CONCLUSIONS: Findings suggest that an Internet-delivered intervention yielded a modest reduction in weight status that continued 4 months after treatment and that ED attitudes/behaviors were not significantly improved. Group differences on weight loss were not sustained at 4-month follow-up because of parallel improvements in the groups. Future studies are needed to improve program adherence and to further explore the efficacy of Internet-delivery of weight control programs for adolescents.