Neuroimmunological effects of omega-3 fatty acids on migraine: a review.

Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.

Unveiling the age-related dynamics in Sjögren's syndrome: Insights from heart rate variability and autonomic function.

BACKGROUND: Sjögren's Syndrome (SS), mainly affecting women in their midlife, is characterized by persistent inflammation in glands producing tears and saliva, often leading to significant complications. This study investigates the differences in autonomic system functioning between individuals with SS and healthy controls. METHODS: From April 2019 to December 2022, 329 diagnosed primary SS (pSS) patients and 30 healthy controls were enrolled at Taipei Veterans General Hospital, Taipei, Taiwan. The study assessed autonomic nervous system functioning using various HRV metrics. Participants were divided based on age and AECG criteria, including salivary gland biopsy and autoantibody status. RESULTS: Significant differences in Heart Rate Variability (HRV) were observed between pSS patients and healthy controls. The total power index was notably lower in pSS patients (4.98 ± 1.29) than in controls (5.54 ± 1.21, p = .022). Additionally, Vagal (VAG) activity was significantly reduced in the pSS group (4.95 ± 1.33) compared to the healthy control group (5.47 ± 1.19, p = .041). Age-stratified analysis highlighted that the ≤50 years pSS group had a higher heart rate (77.74 ± 10.42) compared to the >50 years group (73.86 ± 10.35, p = .005). This group also showed a higher total power index (5.78 ± 1.30) versus the >50 years group (4.68 ± 1.19, p < .001), and significantly lower VAG activity (4.70 ± 1.26, p = .007) compared to healthy controls. Furthermore, the Standard Deviation of Normal-to-Normal Intervals (SDNN) was greater in the ≤50 years SS group (44.45 ± 37.12) than in the >50 years group (33.51 ± 26.18, p = .007). In pSS patients, those positive for both salivary gland biopsy and autoantibodies demonstrated a lower Total Power (4.25 ± 1.32) and R-wave validity (93.50 ± 4.79, p < .05) than other groups, suggesting more severe autonomic imbalance. The R-R interval variation (RRIV) was also significantly higher in this dual-positive group (696.10 ± 975.41, p < .05). Additionally, the ESSPRI for dryness was markedly higher in the dual-positive group (8.10 ± 1.45, p < .05), indicating more severe symptoms. These findings reveal significant variations in autonomic function in SS patients, especially in those with dual-positive biopsy and autoantibody status. CONCLUSION: This study demonstrates significant autonomic dysfunction in pSS patients compared to healthy controls, particularly in those positive for both salivary gland biopsy and autoantibodies. The age-stratified analysis further emphasizes the impact of aging on autonomic system functioning in pSS, suggesting a need for age-specific management approaches in pSS patient care.

Association Between Herpes Simplex Virus II Infection and Rheumatoid Arthritis in US Adults: A Population-Based Propensity Score-Matching Study.

BACKGROUND/OBJECTIVE: The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. METHODS: A case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. RESULTS: The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. CONCLUSIONS: This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.

The immediate effects of lavender-based essential oil inhalation on subsequent polysomnography in people with poor sleep quality.

BACKGROUND: Although aromatherapy is considered an adjuvant therapy to promote sleep quality, few objective sleep testing instruments can confirm the effects of aromatherapy on sleep physiology. The purpose of this study was to confirm and compare the immediate effects of a single lavender essential oil (SLEO) group to a complex lavender essential oil (CLEO) group by objective polysomnography (PSG) recordings. METHODS: Participants were randomly divided into the SLEO group and CLEO group in this single-blind trial to explore the sleep effect of essential oil aroma. All the participants completed the sleep-related questionnaires and underwent two consecutive nights of PSG recordings, who had one night without aromatherapy and one night with one of the two aromas randomly assigned to them. RESULTS: Total of 53 participants were recruited for this study, 25 participants were in the SLEO group, and 28 were in the CLEO group. Baseline characteristics and sleep-related questionnaires were similar in both groups. Both SLEO and CLEO extended the total sleep time (TST) (Δ = 43.42 and 23.75 minutes, respectively) and sleep period time (SPT) (Δ = 38.86 and 24.07 minutes, respectively). The SLEO group further improved sleep efficiency and increased the amounts of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and decreased spontaneous arousals. However, there was no significant difference in PSG parameters between the SLEO and CLEO groups. CONCLUSION: Both SLEO and CLEO extended TST and SPT, with no significant differences between these two groups. These results warrant practical applications and merit future studies (Clinical trial registration: ClinicalTrials.gov : NCT03933553).

Integrated therapy decreases the mortality of patients with polymyositis and dermatomyositis: A Taiwan-wide population-based retrospective study.

ETHNOPHARMACOLOGICAL RELEVANCE: The issue of whether integrated treatment with conventional medicine (CM) and herbal medicine (HM) can reduce mortality in patients with polymyositis/dermatomyositis (PM/DM) had not been addressed. AIM OF THE STUDY: In this study, we investigated the effect of integrated therapy on mortality in a retrospective PM/DM cohort in the Taiwan National Health Insurance Research Database (NHIRD). MATERIALS AND METHODS: Patients with PM/DM were retrospectively enrolled from the PM/DM Registry of Catastrophic Illnesses cohort in the Taiwan NHIRD between 1997 and 2011. The patients were divided into an integrated medicine (IM) group that received CM and HM and a non-IM group that received CM alone. The Cox proportional hazards regression model and Kaplan-Meier method were used to evaluate the hazard ratio (HR) for mortality. RESULTS: Three hundred and eighty-five of 2595 patients with newly diagnosed PM/DM had received IM and 99 had received non-IM. The adjusted HR for mortality was lower in the IM group than in the non-IM group (0.42, 95% confidence interval 0.26-0.68, p < 0.001). The adjusted HR for mortality was also lower in the IM group that had received CM plus HM than in the group that received CM alone (0.48, 95% confidence interval 0.28-0.84, p < 0.05). The core pattern of HM prescriptions integrated with methylprednisolone, methotrexate, azathioprine, or cyclophosphamide to decrease mortality included "San-Qi" (Panax notoginseng), "Bai-Ji" (Bletilla striata), "Chen-Pi" (Citrus reticulata), "Hou-Po" (Magnolia officinalis), and "Dan-Shan" (Salvia miltiorrhiza). CONCLUSION: Integrated therapy has reduced mortality in patients with PM/DM in Taiwan. Further investigation of the clinical effects and pharmaceutical mechanism involved is needed.

The Evaluation of Professional Divisions of Traditional Chinese Medicine in Taiwan through Patient Visit Records of 2012.

For decades, professional divisions have been represented as the main structural divisions in Western medicine throughout the world. In Taiwan, medical policymakers are also interested in designing professional divisions of traditional Chinese medicine (TCM). Therefore, this study evaluated the current status and potentiality of professional divisions of TCM in Taiwan using data from the year 2012 obtained from the National Health Insurance Research Database; the database provides information regarding age and gender of TCM physicians (TCMPs); total visit counts; contracted medical institution codes; groupings of diseases classified under International Classification of Diseases, Ninth Revision, Clinical Modification codes; numbers of children and female patients seeking treatment; and claim disposition codes used by each TCMP. The results indicated that there were 5522 TCMPs in 2012, and 4876 (90.3%) TCMPs practiced in primary clinics. The proportions of pediatric visits to these TCMPs were mostly below 0.2, and acupuncture or traumatology-related visit proportions were below 0.5. Only a few of the studied Taiwan-based TCMPs practiced gynecology and pediatrics, but most of them performed "internal medicine", or "acupuncture" or "traumatology" treatments. Thus, the number of TCM specialists practicing gynecology or pediatrics is insufficient, indicating that a policy that forms professional divisions of TCM practitioners in Taiwan should be reconsidered.

Integrated therapy improve urinary total protein in patients with lupus nephritis: A case report.

OBJECTIVES: To report on the potential effectiveness of Chinese herbal medicine (CHM) as part of an integrated treatment for lupus nephritis. CLINICAL FEATURES AND OUTCOME: A 55-year-old female with systemic lupus erythematosus had experienced bilateral lower-limbs edema for half a year. Her urinary total protein (M-TP) was 1367.9 mg/24 h. Lupus nephritis (LN) was suspected by the Division of Rheumatology without a renal biopsy. Oral corticosteroid medication did not improve the edema; therefore, the patient requested CHM for integrated therapy, and was subsequently treated for seven months with a modified CHM prescription mainly composed of Zhi-Bo-Di-Huang-Wan, Gui-Shao-Zhi-Mu-Tang, and Zhu-Ling-Tang. After three days of CHM, her bilateral lower-limbs edema significantly improved, and after 143 days, her M-TP decreased from 1367.9 mg/24 h to 143.6 mg/24 h. CONCLUSIONS: Integrated therapy could significantly improve proteinuria by reducing this LN patients' urinary total protein, which further implies that CHM may have a protective effect against the progression of LN in this patient.

Complementary Chinese Herbal Medicine Therapy Improves Survival of Patients With Pancreatic Cancer in Taiwan: A Nationwide Population-Based Cohort Study.

BACKGROUND: Pancreatic cancer is a difficult-to-treat cancer with a late presentation and poor prognosis. Some patients seek traditional Chinese medicine (TCM) consultation. We aimed to investigate the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. METHODS: We included all patients with pancreatic cancer who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 1997 and 2010. We used 1:1 frequency matching by age, sex, the initial diagnostic year of pancreatic cancer, and index year to enroll 386 CHM users and 386 non-CHM users. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. RESULTS: According to the Cox hazard ratio model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity, and treatments, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.67, 95% CI = 0.56-0.79). Those who received CHM therapy for more than 90 days had significantly lower hazard ratios of mortality risk than non-CHM users (90- to 180-day group: adjusted HR = 0.56, 95% CI = 0.42-0.75; >180-day group: HR = 0.33, 95% CI = 0.24-0.45). The survival probability was higher for patients in the CHM group. Bai-hua-she-she-cao (Herba Oldenlandiae; Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum Combination) were the most commonly used single herb and Chinese herbal formula, respectively. CONCLUSIONS: Complementary Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trial is warranted.

Traditional Chinese Medicine Use among Patients with Psoriasis in Taiwan: A Nationwide Population-Based Study.

Traditional Chinese medicine (TCM) has long been used for patients with psoriasis. This study aimed to investigate TCM usage in patients with psoriasis. We analyzed a cohort of one million individuals representing the 23 million enrollees randomly selected from the National Health Insurance Research Database in Taiwan. We identified 28,510 patients newly diagnosed with psoriasis between 2000 and 2010. Among them, 20,084 (70.4%) patients were TCM users. Patients who were female, younger, white-collar workers and lived in urbanized area tended to be TCM users. The median interval between the initial diagnosis of psoriasis to the first TCM consultation was 12 months. More than half (N = 11,609; 57.8%) of the TCM users received only Chinese herbal medicine. Win-qing-yin and Bai-xian-pi were the most commonly prescribed Chinese herbal formula and single herb, respectively. The core prescription pattern comprised Mu-dan-pi, Wen-qing-yin, Zi-cao, Bai-xian-pi, and Di-fu-zi. Patients preferred TCM than Western medicine consultations when they had metabolic syndrome, hepatitis, rheumatoid arthritis, alopecia areata, Crohn's disease, cancer, depression, fatty liver, chronic airway obstruction, sleep disorder, and allergic rhinitis. In conclusion, TCM use is popular among patients with psoriasis in Taiwan. Future clinical trials to investigate its efficacy are warranted.

Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments.

LC is an herbal remedy effectively reduced therapeutic dosage of glucocorticoid for systemic lupus erythematosus (SLE) patients in clinical trial (ISRCTN81818883). This translational research examined the impact of LC on biomarkers of endothelial injury in the enrolled subjects. Fifty seven patients with SLE were randomized to receive standard treatment without or with LC supplements. Blood samples were taken serially for quantification of endothelial progenitor cells (EPCs), circulating endothelial cells (CECs) and serological factors. The proportion of EPCs in the placebo group continued to increase during trial and was further elevated after withdrawal of standard treatment. The EPC ratio of LC group remained stationary during the entire observation period. The CEC ratio in placebo group exhibited an increasing trend whereas that in LC group declined. The ratio of apoptotic CECs had an increasing trend in both groups, to a lesser extent in LC group. After treatment, the levels of VEGF and IL-18 have a trend declined to a level lower in the LC group than the placebo group. No significant alteration was noted in serum levels of IFN-α, IL-1ß and IL-6. The reduction of the steroid dosage by adding LC might be correlated with less extensive endothelial injury in SLE patients.

Adjunctive Chinese Herbal Medicine therapy improves survival of patients with chronic myeloid leukemia: a nationwide population-based cohort study.

Despite good clinical results of current drugs, a good reason still exists to search for additional therapies for the management of Chronic Myeloid Leukemia (CML). Chinese Herbal Medicine (CHM) has thus far been overlooked by researchers and no data exists on the subject. We studied the impact of adjunctive CHM on the disease course of CML, using mortality as the major outcome measurement. We used the Taiwanese National Health Insurance Research Database to perform a nationwide population-based cohort study. Our study included CML patients diagnosed between 2000 and 2010. We matched groups according to age, sex, Charlson Comorbidity Index (CCI) score and use of imatinib, and compared the Hazard Ratios (HR) of CHM group and non-CHM users, as well as characterized trends of prescriptions used for treating CML. 1371 patients were diagnosed with CML in the years examined, of which 466 were included in to this study. We found that the HR of CHM group was significantly lower compared to non-CHM groups (0.32, 95% CI 0.22-0.48, P < 0.0001). We also established that this association between reduced HR was dose-dependent, and the longer CHM users received prescriptions, the lower the HR (P < 0.01). We also analyzed the most commonly used herbal products as well as the HR associated to their use, thus providing future research candidates. Our results supply a strong reason to assume that when administered by properly trained physicians, CHM may have a substantial positive impact on the management of CML.

Chinese herbal prescriptions for osteoarthritis in Taiwan: analysis of National Health Insurance dataset.

BACKGROUND: Chinese herbal medicine (CHM) has been commonly used for treating osteoarthritis in Asia for centuries. This study aimed to conduct a large-scale pharmaco-epidemiologic study and evaluate the frequency and patterns of CHM used in treating osteoarthritis in Taiwan. METHODS: A complete database (total 22,520,776 beneficiaries) of traditional Chinese medicine (TCM) outpatient claims offered by the National Health Insurance program in Taiwan for the year 2002 was employed for this research. Patients with osteoarthritis were identified according to the diagnostic code of the International Classification of Disease among claimed visiting files. Corresponding prescription files were analyzed, and an association rule was applied to evaluate the co-prescription of CHM for treating osteoarthritis. RESULTS: There were 20,059 subjects who visited TCM clinics for osteoarthritis and received a total of 32,050 CHM prescriptions. Subjects between 40 and 49 years of age comprised the largest number of those treated (19.2%), followed by 50-59 years (18.8%) and 60-69 years group (18.2%). In addition, female subjects used CHMs for osteoarthritis more frequently than male subjects (female: male = 1.89: l). There was an average of 5.2 items prescribed in the form of either an individual Chinese herb or formula in a single CHM prescription for osteoarthritis. Du-zhong (Eucommia bark) was the most commonly prescribed Chinese single herb, while Du-huo-ji-sheng-tang was the most commonly prescribed Chinese herbal formula for osteoarthritis. According to the association rule, the most commonly prescribed formula was Du-huo-ji-sheng-tang plus Shen-tong-zhu-yu-tang, and the most commonly prescribed triple-drug combination was Du-huo-ji-sheng-tang, Gu-sui-pu (Drynaria fortune (Kunze) J. Sm.), and Xu-Duan (Himalaya teasel). Nevertheless, further clinical trials are needed to evaluate the efficacy and safety of these CHMs for treating osteoarthritis. CONCLUSIONS: This study conducted a large scale pharmaco-epidemiology survey of Chinese herbal medicine use in OA patients by analyzing the NHIRD in Taiwan in year 2002.