What clinical trials of drugs or supplements have evaluated outcomes in apoe4 (apoe e4) -positive patients?

Answer from top 10 papers

The provided context does not specifically mention clinical trials evaluating outcomes in APOE4 (Apolipoprotein E4) positive patients. APOE4 is a variant of the gene Apolipoprotein E (APOE) which is associated with an increased risk for Alzheimer's disease and cardiovascular diseases. The papers provided focus on the interactions between dietary supplements and various drugs, their safety, and their efficacy in different patient populations, including those with cardiovascular diseases and cancer, but they do not explicitly address trials with APOE4-positive patients.
Given the absence of direct information regarding APOE4-positive patients in the context provided, it is not possible to draw conclusions or provide a summary of clinical trials that have evaluated outcomes specifically in this subgroup. The papers discuss the broader implications of supplement-drug interactions and their effects on health outcomes in general populations or populations with specific conditions such as colorectal cancer, cardiovascular diseases, and those undergoing chemotherapy (Chiba et al., 2014; Donaldson & Touger-Decker, 2013; Haron et al., 2020; Kanji et al., 2012; Khan et al., 2019; Mccarthy et al., 2020; Redd et al., 2022; Sprouse & Breemen, 2015; Wolf et al., 2012; Ye et al., 2023).
In summary, the context provided does not contain information on clinical trials that have specifically evaluated outcomes in APOE4-positive patients. The papers instead offer insights into the potential benefits and risks associated with the use of dietary supplements in conjunction with pharmaceutical agents in various patient populations, highlighting the importance of careful management of potential interactions to ensure patient safety and treatment efficacy.

Source Papers

Inappropriate usage of dietary supplements in patients by miscommunication with physicians in Japan.

Recently, people have used dietary supplements not only for nutritional supplementation, but also for treatment of their diseases. However, use of dietary supplements to treat diseases, especially with medications, may cause health problems in patients. In this study, we investigated use of dietary supplements in patients in Japan. This survey was conducted from January to December 2012, and was completed by 2732 people, including 599 admitted patients, 1154 ambulatory patients, and 979 healthy subjects who attended a seminar about dietary supplements. At the time of the questionnaire, 20.4% of admitted patients, 39.1% of ambulatory patients, and 30.7% of healthy subjects were using dietary supplements, which including vitamin/mineral supplements, herbal extracts, its ingredients, or food for specified health uses. The primary purpose for use in all groups was health maintenance, whereas 3.7% of healthy subjects, 10.0% of ambulatory patients, and 13.2% of admitted patients used dietary supplements to treat diseases. In addition, 17.7% of admitted patients and 36.8% of ambulatory patients were using dietary supplements concomitantly with their medications. However, among both admitted patients and ambulatory patients, almost 70% did not mention dietary supplement use to their physicians. Overall, 3.3% of all subjects realized adverse effects associated with dietary supplements. Communication between patients and physicians is important to avoid health problems associated with the use of dietary supplements.

Open Access
Navigating herbal dietary supplements: Oral chemotherapy drug interactions in a community cancer center.

e19239 Background: The number of FDA-approved oral chemotherapy medications has continued to increase as has their incorporation into cancer treatment plans. Oncology pharmacists play an integral role in assessing and navigating drug interactions for patients. At Southcoast Centers for Cancer Care (SCCC), oncology pharmacists meet with patients to review/counsel on newly initiated oral therapy. One of the areas assessed during the visit is the use of herbal nutritional supplements. Pharmacists utilize available institutional resources to assess potential interactions and collaborate with the University of Rhode Island (URI), Drug Information Services (DIS), when information is not readily available. Methods: Patient responses about utilization of herbal dietary supplements during pharmacist-patient counseling sessions were assessed. All positive responses triggered a drug-supplement interaction screen. Number of patients taking herbal dietary supplements was tabulated and their use was characterized. Results: From October 2016-June 2019, 187 patients were counseled. Of these, 44/187 (24%) were taking herbal dietary supplements. SCCC pharmacists consulted the URI DIS on 10/44 (23%) patients to assist in identifying, researching, and recommending a care plan. The most frequently used supplements were melatonin and marijuana/CBD oil. The most frequently used supplements that required further consultation included curcumin. Conclusions: Consistent with findings from the general population taking prescription medications, we found that approximately 25% of patients taking oral chemotherapeutic medications were also actively taking herbal dietary supplements. Little data exists regarding oral chemotherapy agents and herbal dietary supplement interactions. Careful questioning/review/research of potential interactions is needed to prevent interactions and maximize effectiveness of oral chemotherapy.

Self Medication and Use of Dietary Supplements in Adult Patients with Endocrine and Metabolic Disorders

Patients often use dietary supplements in addition to the therapies prescribed by their physicians. This self medication is often not listed in the drug history. We supposed that people, who are more afraid of co-morbidities or diabetes late complications and who exhibit a higher fear of the potential side effects of prescribed drugs, are more inclined to use dietary supplements. We checked the use of dietary supplements with a standardised questionnaire in patients treated in a centre for endocrinology and metabolic diseases. Demographic and clinical data were taken from the electronic health record EMIL®. A total of 428 patients (51.4% women), mean age 58.3 years, completed the standardised questionnaire. Supplements were used by 41%: Mineral nutrients 60.2%, vitamins 56.8%, "other supplements" (e. g. omega-3-fatty acids, antidiabetic agents) 43.1% and medical herbs 35.1%. The users of supplements were predominantly women (p<0.001), non-smokers (p=0.004), persons with frequent medical appointments (p=0.014) and with a negative attitude towards the effectiveness of the physician prescribed medication (p=0.012). Patients with diabetes do not use supplements more often than patients without. The use of dietary supplements was not associated with patients' fear to develop co-morbidities of existing diseases (p=0.132) or a higher fear of side effects of prescribed drugs (p=0.099). Nearly half of the patients in a centre for endocrinology and metabolic diseases use self medications with dietary supplements. There is no association between the fear of co-morbidities or side effects of physicians prescribed drugs and a self medication with dietary supplements.

Comparative Effects of Different Nutritional Supplements on Inflammation, Nutritional Status, and Clinical Outcomes in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis.

Nutritional supplements have been widely used in colorectal cancer (CRC) patients. The aim of this network meta-analysis (NMA) was to compare the effects of different nutritional supplements on inflammation, nutritional status, and clinical outcomes in CRC patients. Four electronic databases were searched until December 2022. Randomized controlled trials (RCTs) comparing nutritional supplements of omega-3 fatty acids (omega-3), arginine, vitamin D, glutamine, probiotics, or their combinations with placebo or standard treatment were selected. The outcomes were inflammatory indicators, nutritional indicators, and clinical outcomes. A random-effects Bayesian NMA was performed to rank the effect of each supplement. In total, 34 studies involving 2841 participants were included. Glutamine was superior in decreasing tumor necrosis factor-α (MD -25.2; 95% CrI [-32.62, -17.95]), whereas combined omega-3 and arginine supplementation was more effective in decreasing interleukin-6 (MD -61.41; 95% CrI [-97.85, -24.85]). No nutritional supplements significantly maintained nutritional indicators in CRC patients. Regarding clinical outcomes, glutamine ranked highest in reducing the length of hospital stay (MD -3.71; 95% CrI [-5.89, -1.72]) and the incidence of wound infections (RR 0.12; 95% CrI [0, 0.85]), and probiotics were rated as best in reducing the incidence of pneumonia (RR 0.38; 95% CrI [0.15, 0.81]). Future well-designed RCTs are needed to further confirm these findings.

Open Access
Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements.

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug-botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John's wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug-botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug-botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism.

Open Access
Detecting Use of Patient Dietary Supplements in Free Text Clinical Notes

Abstract Background: There is widespread use of dietary supplements, some prescribed but many taken without a physician’s guidance. There are many potential interactions of supplements with both over the counter and prescription medications. Many of these are not known to the patient. Documentation of supplement use is incomplete in structured medical records, however additional information about supplements is often found in unstructured clinical notes. Natural language processing (NLP) techniques can be used to detect supplement use in these notes. Methods: We study a group of 377 patients from three healthcare systems and develop an NLP system to detect supplement use. We then use surveys of these patients to investigate correlation between self-reported supplement use and NLP predictions from the clinical notes. Results: We attain an F1 score of 0.914 on creation of the model for all supplements. Individual supplement detection had variable correlation with survey responses, ranging from and F1 of 0.83 for calcium, to F1 of 0.39 for folic acid. Conclusions: We demonstrate the ability to capture the use of dietary supplements from free text clinical notes, enabling clinical studies including drug interactions and outcomes research. Generalizability is demonstrated due to the use of notes from a nationwide electronic health record system. We also show that patients from three healthcare systems self-reported supplement use that often contradicted what was recorded in the clinical record.

Open Access
Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map.

The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence). Suboptimal quality and certainty of evidence. Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. None.

Interactions of commonly used dietary supplements with cardiovascular drugs: a systematic review.

BackgroundThe objective of this systematic review was to examine the benefits, harms and pharmacokinetic interactions arising from the co-administration of commonly used dietary supplements with cardiovascular drugs. Many patients on cardiovascular drugs take dietary supplements for presumed benefits and may be at risk for adverse supplement-drug interactions.MethodsThe Allied and Complementary Medicine Database, the Cochrane Library, EMBASE, International Bibliographic Information on Dietary Supplements and MEDLINE were searched from the inception of the review to October 2011. Grey literature was also reviewed.Two reviewers independently screened records to identify studies comparing a supplement plus cardiovascular drug(s) with the drug(s) alone. Reviewers extracted data using standardized forms, assessed the study risk of bias, graded the strength of evidence and reported applicability.ResultsEvidence was obtained from 65 randomized clinical trials, 2 controlled clinical trials and 1 observational study. With only a few small studies available per supplement, evidence was insufficient for all predefined gradable clinical efficacy and harms outcomes, such as mortality and serious adverse events. One long-term pragmatic trial showed no benefit from co-administering vitamin E with aspirin on a composite cardiovascular outcome. Evidence for most intermediate outcomes was insufficient or of low strength, suggesting no effect. Incremental benefits were noted for triglyceridemia with omega-3 fatty acid added to statins; and there was an improvement in levels of high-density lipoprotein cholesterol with garlic supplementation when people also consumed nitratesConclusionsEvidence of low-strength indicates benefits of omega-3 fatty acids (plus statin, or calcium channel blockers and antiplatelets) and garlic (plus nitrates or warfarin) on triglycerides and HDL-C, respectively. Safety concerns, however, persist.

Open Access
Possible Herb-Drug Interaction Risk of Some Nutritional and Beauty Supplements on Antiretroviral Therapy in HIV Patients

This study was carried out to assess the drug interaction potential of a variety of beauty and sports/nutritional supplements when co-administered with antiviral drug therapy, especially anti-HIV drugs. Ethanolic extracts of seven dietary supplements (two beauty products, three nutritional protein supplement products and two weight loss/body building products) were examined in human liver cells (HepG2 cells and primary hepatocytes) for their influence on the hepatic metabolism of five antiviral drugs (elvitegravir, rilpivirine, tenofovir, dolutegravir, and cobicistat), all of which are substrates for a key drug metabolizing enzyme CYP3A4. Our results showed that six of the seven supplements caused a 1.5 – 2 fold induction in PXR transcriptional activity in HepG2 cells. PXR regulates the expression of key drug metabolizing enzymes including CYP3A4. Follow up studies indicated a 1.5 – 3 fold induction in CYP3A4 enzyme activity in HepG2 cells treated with these supplements. We further investigated the effects of the supplement on the metabolism of above mentioned anti-viral drugs in HepG2 cells and primary hepatocytes. Of the five drugs, rilpivirine and dolutegravir metabolism was increased by up to 2-folds over the no supplement control by some of the supplements. Our findings indicate that concomitant consumption of these products with anti-HIV drugs may compromise the efficacy of antivirals therapy due to supplement-induced metabolism via induction of CYP3A4 activity.