A Pharmacokinetic Study of Different Quercetin Formulations in Healthy Participants: A Diet-Controlled, Crossover, Single- and Multiple-Dose Pilot Study.

This study aimed to evaluate the blood concentrations of quercetin in healthy participants after the administration of different formulations in single- and multiple-dose phases. Ten healthy adults (males, 5; females, 5; age 37 ± 11 years) participated in a diet-controlled, crossover pilot study. Participants received three different doses (250 mg, 500 mg, or 1000 mg) of quercetin aglycone orally. In the single-dose study, blood concentrations (AUC0-24 and Cmax) of standard quercetin were compared with those of LipoMicel®-a food-grade delivery form of quercetin. In the multiple-dose study, blood concentrations of formulated quercetin were observed over 72 h, after repeated doses of LipoMicel (LM) treatments. The AUC0-24 ranged from 77.3 to 1128.9 ng·h/ml: LM significantly increased blood concentrations of quercetin by 7-fold (LM 500) compared to standard quercetin, when tested at the same dose, over 24 h (p < 0.001); LM administered at a higher dose (LM 1000) achieved 15-fold higher absorption (p < 0.001); LM tested at half a dose of standard quercetin increased concentration by approx. 3-fold (LM 250). Quercetin blood concentrations were attained over 72 h. The major metabolites measured in the blood were methylated, sulfate, and glutathione (GSH) conjugates of quercetin. Significant differences in concentrations between quercetin conjugates (sulfate vs. methyl vs. GSH) were observed (p < 0.001). Data obtained from this study suggest that supplementation with LipoMicel® is a promising strategy to increase the absorption of quercetin and its health-promoting effects in humans. However, due to the low sample size in this pilot study, further research is still warranted to confirm the observations in larger populations. This trial is registered with NCT05611827.

Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice.

In times of health crisis, including the current COVID-19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self-care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well-being. Newly emerging viral infections, specifically COVID-19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate-yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.

Multi-Criteria Decision Analysis Model for Assessing the Risk from Multi-Ingredient Dietary Supplements (MIDS).

Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight loss, and to maintain health. Adverse events, including cardiovascular (CV) effects, have been reported in military personnel taking supplements. Previous research determined that ingestion of multi-ingredient dietary supplements (MIDS), can lead to signals of safety concerns. Therefore, to assess the safety of MIDS, the Department of Defense via a contractor explored the development of a model-based risk assessment tool. We present a strategy and preliminary novel multi-criteria decision analysis (MCDA)-based tool for assessing the risk of adverse CV effects from MIDS. The tool integrates toxicology and other relevant data available on MIDS; likelihood of exposure, and biologic plausibility that could contribute to specific aspects of risk.Inputs for the model are values of four measures assigned based on the available evidence supplemented with the opinion of experts in toxicology, modeling, risk assessment etc. Measures were weighted based on the experts' assessment of measures' relative importance. Finally, all data for the four measures were integrated to provide a risk potential of 0 (low risk) to 100 (high risk) that defines the relative risk of a MIDS to cause adverse reactions.We conclude that the best available evidence must be supplemented with the opinion of experts in medicine, toxicology and pharmacology. Model-based approaches are useful to inform risk assessment in the absence of data. This MCDA model provides a foundation for refinement and validation of accuracy of the model predictions as new evidence becomes available.

Safety and performance benefits of arginine supplements for military personnel: a systematic review.

CONTEXT: Dietary supplements are widely used by military personnel and civilians for promotion of health. OBJECTIVE: The objective of this evidence-based review was to examine whether supplementation with l-arginine, in combination with caffeine and/or creatine, is safe and whether it enhances athletic performance or improves recovery from exhaustion for military personnel. DATA SOURCES: Information from clinical trials and adverse event reports were collected from 17 databases and 5 adverse event report portals. STUDY SELECTION: Studies and reports were included if they evaluated the safety and the putative outcomes of enhanced performance or improved recovery from exhaustion associated with the intake of arginine alone or in combination with caffeine and/or creatine in healthy adults aged 19 to 50 years. DATA EXTRACTION: Information related to population, intervention, comparator, and outcomes was abstracted. Of the 2687 articles screened, 62 articles meeting the inclusion criteria were analyzed. Strength of evidence was assessed in terms of risk of bias, consistency, directness, and precision. RESULTS: Most studies had few participants and suggested risk of bias that could negatively affect the results. l-Arginine supplementation provided little enhancement of athletic performance or improvements in recovery. Short-term supplementation with arginine may result in adverse gastrointestinal and cardiovascular effects. No information about the effects of arginine on the performance of military personnel was available. CONCLUSIONS: The available information does not support the use of l-arginine, either alone or in combination with caffeine, creatine, or both, to enhance athletic performance or improve recovery from exhaustion. Given the information gaps, an evidence-based review to assess the safety or effectiveness of multi-ingredient dietary supplements was not feasible, and therefore the development of a computational model-based approach to predict the safety of multi-ingredient dietary supplements is recommended.

Acupuncture practice acts: a profession's growing pains.

State legislation that authorizes any healthcare profession is known as the Practice Act. In order for a profession to establish a recognizable national presence and be integrated into mainstream medicine, all the state Practice Acts must evidence consistency. The extent to which state Practice Acts fail to exhibit consistency can inhibit the ability of the profession to grow and become successful. We looked at the histories of other health professions, along with the 45 acupuncture Practice Acts in the USA, in order to understand the time worn paths that lead to integration in the mainstream and how the acupuncture profession might benefit.

Multivitamin/multimineral supplements for cancer prevention: implications for primary care practice.

There is a popular belief that multivitamin and mineral (MVM) supplements can help prevent cancer and other chronic diseases. Studies evaluating the effects of MVM supplements on cancer risk have largely been observational, with considerable methodologic limitations, and with conflicting results. We review evidence from the few available randomized, controlled trials that assessed the effects of supplements containing individual vitamins, a combination of a few select vitamins, or complete MVM supplements, with a focus on the recent Physicians' Health Study II (PHS II). PHS II is a landmark trial that followed generally healthy middle-aged and older men (mean age 64 years) who were randomized to daily MVM supplementation for a mean duration of 11 years. Men taking MVMs experienced a statistically significant 8% reduction in incidence of total cancer (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.86-0.998; p = 0.04). Men with a history of cancer derived an even greater benefit: cancer incidence was 27% lower with MVM supplementation versus placebo in this subgroup (HR: 0.73; 95% CI: 0.56-0.96; p = 0.02). Positive results of PHS II contrast with randomized studies of individual vitamins or small combinations of vitamins, which have largely shown a neutral effect, and in some cases, an adverse effect, on cancer risk. The results of PHS II may have a considerable public health impact, potentially translating to prevention of approximately 68 000 cancers per year if all men were to use similar supplements, and to an even greater benefit with regard to secondary prevention of cancer.

Evidence-based evaluation of potential benefits and safety of beta-alanine supplementation for military personnel.

This Department of Defense-sponsored evidence-based review evaluates the safety and putative outcomes of enhancement of athletic performance or improved recovery from exhaustion in studies involving beta-alanine alone or in combination with other ingredients. Beta-alanine intervention studies and review articles were collected from 13 databases, and safety information was collected from adverse event reporting portals. Due to the lack of systematic studies involving military populations, all the available literature was assessed with a subgroup analysis of studies on athletes to determine if beta-alanine would be suitable for the military. Available literature provided only limited evidence concerning the benefits of beta-alanine use, and a majority of the studies were not designed to address safety. Overall, the strength of evidence in terms of the potential for risk of bias in the quality of the available literature, consistency, directness, and precision did not support the use of beta-alanine by military personnel. The strength of evidence for a causal relation between beta-alanine and paresthesia was moderate.

Integrating dietary supplements into cancer care.

Many studies confirm that a majority of patients undergoing cancer therapy use self-selected forms of complementary therapies, mainly dietary supplements. Unfortunately, patients often do not report their use of supplements to their providers. The failure of physicians to communicate effectively with patients on this use may result in a loss of trust within the therapeutic relationship and in the selection by patients of harmful, useless, or ineffective and costly nonconventional therapies when effective integrative interventions may exist. Poor communication may also lead to diminishment of patient autonomy and self-efficacy and thereby interfere with the healing response. To be open to the patient's perspective, and sensitive to his or her need for autonomy and empowerment, physicians may need a shift in their own perspectives. Perhaps the optimal approach is to discuss both the facts and the uncertainty with the patient, in order to reach a mutually informed decision. Today's informed patients truly value physicians who appreciate them as equal participants in making their own health care choices. To reach a mutually informed decision about the use of these supplements, the Clinical Practice Committee of The Society of Integrative Oncology undertook the challenge of providing basic information to physicians who wish to discuss these issues with their patients. A list of leading supplements that have the best suggestions of benefit was constructed by leading researchers and clinicians who have experience in using these supplements. This list includes curcumin, glutamine, vitamin D, Maitake mushrooms, fish oil, green tea, milk thistle, Astragalus, melatonin, and probiotics. The list includes basic information on each supplement, such as evidence on effectiveness and clinical trials, adverse effects, and interactions with medications. The information was constructed to provide an up-to-date base of knowledge, so that physicians and other health care providers would be aware of the supplements and be able to discuss realistic expectations and potential benefits and risks.

It's time for clinicians to reconsider their proscription against the use of soyfoods by breast cancer patients.

The impact of soyfood intake on breast cancer risk has been intensely investigated. This focus can be attributed to soyfoods being uniquely rich dietary sources of isoflavones. Isoflavones are classified as both phytoestrogens and selective estrogen receptor (ER) modulators. The finding that dietary genistein, the primary soybean isoflavone, stimulates the growth of existing mammary tumors in ovariectomized athymic mice implanted with ER-positive breast cancer cells has led many oncologists to advise their patients against the use of soyfoods. However, the clinical evidence indicates that isoflavone exposure has little effect on markers of breast cancer risk. Furthermore, a pooled analysis that involved 9,514 breast cancer survivors found higher isoflavone intake was associated with a statistically significant 25% reduction in recurrence over the average 7.4-year follow-up period. Given the clinical and epidemiologic data, our position is that clinicians should allow soyfood use by patients for whom soyfoods already represent a normal part of their diet, and should not discourage other breast cancer survivors from moderate consumption.

Dietary supplement use in cancer care: help or harm.

Conventional wisdom generally recommends complete avoidance of all dietary supplements, especially during chemotherapy and radiation. This interdiction persists, in spite of high rates of dietary supplement use by patients throughout all phases of cancer care, and can result in patients' perceptions of physicians as negative, thus leading to widespread nondisclosure of use. A review of the clinical literature shows that some evidence for harm does exist; however, data also exist that show benefit from using certain well-qualified supplements. Physicians should increase their knowledge base about dietary supplement use in cancer and consider all of the data when advising patients. Strategies that are patient-centered and reflect the complete array of available evidence lead to more nuanced messages about dietary supplement use in cancer. This should encourage greater disclosure of use by patients and ultimately increase safety and efficacy for patients choosing to use dietary supplements during cancer care.

Menopausal issues: a national probability sample of US women.

OBJECTIVE: This survey assessed women's reported information sources about menopause, interactions with physicians concerning use of and compliance concerning conventional and alternative therapies for symptoms, and factors determining choices of symptom support. DESIGN: The study was a nationwide probability survey of menopausal women regarding their symptoms, their attitudes toward menopause and concerns about the menopause experience, what they use as sources of information about menopause, their evaluation of healthcare professionals' competence in addressing patients' concerns, self-evaluation of communication with a healthcare professional about concerns, their feelings about herbal remedies and other complementary and alternative medicine treatment options, and what they consider the most important factor(s) in choosing a treatment option for menopause. RESULTS: Physicians were the most common source of menopause information. Physician opinions are more frequently sought than other sources. About 40% of respondents are comfortable with using over-the-counter or herbal remedies for menopausal symptoms. Only 19% had discussed use of herbal supplements with their physicians. CONCLUSION: This study unveiled women's opinions about treatment options for menopause. More in-depth studies regarding efficacy and/or side effects of each available treatment are the relevant next step, given the prevalence of both hormone replacement therapy and alternative therapies and the controversies surrounding them.

Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer.

OBJECTIVE: To evaluate the evidence of the supplements vitamin C and vitamin E for treatment and prevention of cancer. METHODS: Systematic review of trials and meta-analysis. DATA SOURCES AND MAIN RESULTS: Thirty-eight studies showed scant evidence that vitamin C or vitamin E beneficially affects survival. In the ATBC Cancer Prevention Study Group, no statistically significant effect of treatment was seen for any cancer individually, and our pooled relative risk (regardless of tumor type) for alpha-tocopherol alone was 0.91 (95% confidence interval [CI]: 0.74, 1.12). All cause mortality was not significant. In the Linxian General Population Trial, the relative risks for cancer death for vitamin C (combined with molybdenum) was 1.06 (95% CI: 0.92, 1.21) and for vitamin E (combined with beta-carotene and selenium) was 0.87 (95% CI: 0.76, 1.00). We identified only 3 studies that reported statistically significant beneficial results: vitamin C (in combination with BCG) was found to be beneficial in a single trial of bladder cancer and vitamin E (in combination with omega-3 fatty acid) increased survival in patients with advanced cancer. In the ATBC trial, in analyses of 6 individual cancers, the prevention of prostate cancer in subjects treated with alpha-tocopherol was statistically significant (RR=0.64, 95% CI: 0.44, 0.94). CONCLUSIONS: The systematic review of the literature does not support the hypothesis that the use of supplements of vitamin C or vitamin E in the doses tested helps prevent and/or treat cancer in the populations tested. There were isolated findings of benefit, which require confirmation.

Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines.

Herbal medicines are often combinations of botanical extracts that are assumed to have additive or synergistic effects. The purpose of this investigation was to compare the effect of individual botanical extracts with combinations of extracts on prostate cell viability. We then modeled the interactions between botanical extracts in combination isobolographically. Scutellaria baicalensis, Rabdosia rubescens, Panax-pseudo ginseng, Dendranthema morifolium, Glycyrrhiza uralensis and Serenoa repens were collected, taxonomically identified and extracts prepared. Effects of the extracts on cell viability were quantitated in prostate cell lines using a luminescent ATP cell viability assay. Combinations of two botanical extracts of the four most active extracts were tested in the 22Rv1 cell line and their interactions assessed using isobolographic analysis. Each extract significantly inhibited the proliferation of prostate cell lines in a time- and dose-dependent manner except S. repens. The most active extracts, S. baicalensis, D. morifolium, G. uralensis and R. rubescens were tested as two-extract combinations. S. baicalensis and D. morifolium when combined were additive with a trend toward synergy, whereas D. morifolium and R. rubescens together were additive. The remaining two-extract combinations showed antagonism. The four extracts together were significantly more effective than the two-by-two combinations and the individual extracts alone. Combining the four herbal extracts significantly enhanced their activity in the cell lines tested compared with extracts alone. The less predictable nature of the two-way combinations suggests a need for careful characterization of the effects of each individual herb based on their intended use.

Are Ayurvedic herbs for diabetes effective?

OBJECTIVE: To evaluate and synthesize the evidence on the effect of Ayurvedic therapies for diabetes mellitus. DESIGN: Systematic review of trials. MEASUREMENTS AND MAIN RESULTS: We found no study that assessed Ayurvedic as a system of care. Botanical therapy was by far the most commonly studied Ayurvedic treatment. Herbs were studied either singly or as formulas. In all, 993 titles in Western computerized databases and 318 titles identified by hand-searching journals in India were examined, yielding 54 articles reporting the results of 62 studies. The most-studied herbs were G sylvestre, C indica, fenugreek, and Eugenia jambolana. A number of herbal formulas were tested, but Ayush-82 and D-400 were most often studied. Thirty-five of the studies included came from the Western literature, 27 from the Indian. Seven were randomized controlled trials (RCTs) and 10 controlled clinical trials (CCTs) or natural experiments. Twenty-two studies went on to further analysis based on a set of criteria. Of these, 10 were RCTs, CCTs, or natural experiments, 12 were case series or cohort studies. There is evidence to suggest that the herbs C indica, holy basil, fenugreek, and G sylvestre, and the herbal formulas Ayush-82 and D-400 have a glucose-lowering effect and deserve further study. Evidence of effectiveness of several other herbs is less extensive (C tamala, E jambolana, and Momordica charantia). CONCLUSIONS: There is heterogeneity in the available literature on Ayurvedic treatment for diabetes. Most studies test herbal therapy. Heterogeneity exists in the herbs and formulas tested (more than 44 different interventions identified) and in the method of their preparation. Despite these limitations, there are sufficient data for several herbs or herbal formulas to warrant further studies.

Identification of botanicals and potential contaminants through RFLP and sequencing.

Botanical supplements for health enhancement are being increasingly used in the United States, but no safeguards are formally in place to ensure that they are not contaminated with non-efficacious or potentially harmful plant material. A molecular approach, which allows the authentication of botanical ingredients and detection of contaminating plant material by analyzing the ITS-1 region by PCR-RFLP and subsequent sequencing, is described. When using starting material from which DNA can be obtained, this method has the potential for identifying both primary and contaminating plant material in botanical dietary supplements.

A Self-Report Measure of Clinicians' Orientation toward Integrative Medicine.

OBJECTIVE: Patients in the U.S. often turn to complementary and alternative medicine (CAM) and may use it concurrently with conventional medicine to treat illness and promote wellness. However, clinicians vary in their openness to the merging of treatment paradigms. Because integration of CAM with conventional medicine can have important implications for health care, we developed a survey instrument to assess clinicians' orientation toward integrative medicine. STUDY SETTING: A convenience sample of 294 acupuncturists, chiropractors, primary care physicians, and physician acupuncturists in academic and community settings in California. DATA COLLECTION METHODS: We used a qualitative analysis of structured interviews to develop a conceptual model of integrative medicine at the provider level. Based on this conceptual model, we developed a 30-item survey (IM-30) to assess five domains of clinicians' orientation toward integrative medicine: openness, readiness to refer, learning from alternate paradigms, patient-centered care, and safety of integration. PRINCIPAL FINDINGS: Two hundred and two clinicians (69 percent response rate) returned the survey. The internal consistency reliability for the 30-item total scale and the five subscales ranged from 0.71 to 0.90. Item-scale correlations for the five subscales were higher for the hypothesized subscale than other subscales 75 percent or more of the time. Construct validity was supported by the association of the IM-30 total scale score (0-100 possible range, with a higher score indicative of greater orientation toward integrative medicine) with hypothesized constructs: physician acupuncturists scored higher than physicians (71 versus 50, p<.001), dual-trained practitioners scored higher than single-trained practitioners (71 versus 62, p<.001), and practitioners' self-perceived "integrativeness" was significantly correlated (r=0.60, p<.001) with the IM-30 total score. CONCLUSION: This study provides support for the reliability and validity of the IM-30 as a measure of clinicians' orientation toward integrative medicine. The IM-30 survey, which we estimate as requiring 5 minutes to complete, can be administered to both conventional and CAM clinicians.

A national probability survey of American Medical Association gynecologists and primary care physicians concerning menopause.

OBJECTIVE: This survey intended to clarify physicians' understanding of the issues surrounding women, menopause, alternative medicine, and drug therapy for the treatment of menopause. STUDY DESIGN: This study was designed as a national probability sample survey of primary care physicians and gynecologists nationwide. Its focus was to identify major concerns and issues identified by patients about menopause and perceived communication with effectiveness how to communicate with their patients. Physicians were also asked to rate their comfort level in recommending the use of herbal remedies and which herbal remedy they felt comfortable recommending to interested patients. RESULTS: Data indicated that a patient's complaint about menopausal symptoms was the most common factor leading to discussion of menopausal issues with physicians (91%) and that the primary concern to the patient was management of menopausal symptoms. Other factors were controversies about hormone replacement therapy, long-term health implications of menopause, and hormone replacement therapy. Eighty percent of the physician found confusing messages with regard to menopause to be the most challenging aspect in patient communication. The second most challenging issue is "inconclusive data about hormone replacement therapy" (56%). Seventy-six percent of the physicians found "showing sympathy" to be the most important factor for the physicians to communicate effectively with patients, whereas "being honest and open" was the most important patient attitude cited for the same purpose. When it comes to herbal therapy for menopause symptom control, only 4% of the physicians indicated that none of their patients take any remedies. Only 18% were not very comfortable in discussing or recommending herbal therapies, whereas the rest ranged from fairly comfortable to completely comfortable. CONCLUSION: This study has provided data with regard to physician understanding of menopause treatment options and their primary interaction with patients on this issue. More in-depth studies concerning efficacy and/or side effects of each available treatment will be the relevant next step, given the controversies about both hormone replacement therapy and alternative therapies. The relative efficacy, safety, and cost-effectiveness of different treatments should also be put into the context of both clinical diagnosis and physicians' clinical judgment. Attention to comments by physicians and patients with regard to communication may produce better information exchange and trust between patient and physician.

Rabdosia rubescens inhibits breast cancer growth and angiogenesis.

Investigators have shown that PC-SPES is a potent herbal mixture which has often been used by prostate cancer patients. In this study, we examined the inhibitory effects of certain individual components of PC-SPES on the in vitro proliferation of the human breast cancer cells MDA-MB231 and the human umbilical vein endothelial cells (HUVEC). Our data showed that individual components of PC-SPES had varying suppressive effects on cellular proliferation, and that Rabdosia rubescens appeared to be the most potent agent in these assays. Apoptosis was up-regulated by Rabdosia rubescens, as seen in the caspase-9 and TUNEL assays. These effects may be mediated via both the MAPK (mitogen-activated protein kinase) and the Akt kinase pathways. In mouse experiments, the extract from Rabdosia rubescens suppressed breast cancer xenograft size and decreased the tumor vessel density. We conclude that Rabdosia rubescens may potentially be used to treat or prevent breast cancer, and that the extract from this herbal source deserves further studies.