Relevance of Dietary Supplement Use in Gastrointestinal-Cancer-Associated Cachexia.

Cancer cachexia is a multi-organ syndrome with unintentional weight loss, sarcopenia, and systemic inflammation. Gastrointestinal (GI) cancer patients are more susceptible to cachexia development due to impaired nutrient absorption and digestion. Given the widespread availability and relatively low cost of dietary supplements, we examined the evidence and effects of fish oil (omega-3 fatty acids), melatonin, probiotics, and green tea for managing symptoms of GI cancer cachexia. A literature review of four specific supplements was conducted using PubMed, Google Scholar, and CINAHL without a date restriction. Of 4621 available literature references, 26 articles were eligible for review. Fish oil decreased C-reactive protein and maintained CD4+ cell count, while melatonin indicated inconsistent findings on managing cachexia, but was well-tolerated. Probiotics decreased serum pro-inflammatory biomarkers and increased the tolerability of chemotherapy by reducing side effects. Green tea preparations and extracts showed a decreased risk of developing various cancers and did not impact tumor growth, survival, or adverse effects. Among these four supplements, probiotics are most promising for further research in preventing systemic inflammation and maintaining adequate absorption of nutrients to prevent the progression of cancer cachexia. Supplements may benefit treatment outcomes in cancer cachexia without side effects while supporting nutritional and therapeutic needs.

Examining the Psychoactive Differences between Kratom Strains.

Kratom (Mitragyna speciosa) is a Southeast Asian plant containing various alkaloids that induce pharmacological effects in humans. In Western countries, online vendors sell a variety of different kratom strains which are marketed to have distinct effect profiles. However, as of yet such marketing claims are unsubstantiated, and therefore the current study investigated whether differently colored kratom products can induce distinct effects, as self-reported by users. Six hundred forty-four current kratom users were anonymously surveyed to compare the self-reported effects of and motivations for using kratom products sold as red, green, and white strains. Most of the survey respondents were customers of the same kratom vendor, the products of which had been analyzed for their alkaloid content by an independent laboratory. The survey respondents reported distinct subjective experiences for different kratom strains, in a manner congruent with common marketing descriptions. However, the product analyses revealed no significant cross-strain differences in alkaloid content, suggesting that the reported effect differences might be disproportionally influenced by marketing narratives and anecdotal reports. Future studies should engage a more diverse population and include kratom strains from various vendors. Controlled, blinded experiments could assess whether the reported effect differences stem from a placebo effect or from alternative factors, e.g., minor alkaloids and terpenes.

Correlations of kratom (Mitragyna speciosa Korth.) tea bag preparations and reported pharmacological effects.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of herbal tea infusions is widespread in ethnomedicine throughout the world. One such ethnobotanical is kratom (Mitragyna speciosa Korth., Rubiaceae) which has gained considerable interest as an herbal supplement in recent years in the West beyond its native Southeast Asia. Traditional, kratom leaves are either chewed fresh or made into a tea infusion to treat fatigue, pain, or diarrhea. However, dried kratom leaf powder and hydroalcoholic extracts are more commonly used in Western countries, raising the question of exposure to kratom alkaloids and related effects. AIM OF THE STUDY: A specific kratom tea bag product was analyzed for mitragynine content using tea infusion preparation and methanolic extraction. Consumers of both the tea bag product and other kratom products completed an online anonymous survey to determine demographics, kratom use patterns, and self-reported beneficial and detrimental effects. MATERIALS AND METHODS: Kratom tea bag samples were extracted using pH-adjusted water or methanol and analyzed using an established LC-QTOF method. A modified kratom survey was distributed to consumers of the kratom tea bag products and other kratom products over a 14-month period. RESULTS: Tea infusion extraction of tea bag samples resulted in lower mitragynine levels (0.062-0.131% (w/w)) compared to methanolic extraction (0.485-0.616% (w/w)). Kratom tea bag consumers did report similar, although often milder beneficial effects compared to consumers using other kratom products. Overall self-reported health was better among kratom tea bag consumers whereas improvement of a diagnosed medical condition was less in tea bag consumers compared to those using other kratom products. CONCLUSIONS: Traditional tea infusions of Mitragyna speciosa dried leaves provide benefits to consumers despite substantially lower mitragynine content. These effects may be less pronounced but indicate that tea infusions provide a potentially safer formulation compared to more concentrated products.

Kratom Alkaloids: A Blueprint?

Alkaloids from the botanical Mitragyna speciosa (commonly referred to as "kratom") interact with opioid, adrenergic, serotonergic, and other receptors to provide myriad reported effects, including analgesia, energy, improved mood, and relaxation, among others. These alkaloids are complex and unique and may serve as a blueprint for the development of novel molecules to treat various substance use disorders.

Kratom use as more than a "self-treatment".

Background: Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends.Objectives: To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users.Methods: Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions.Results: The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom.Conclusions: Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.

Drug-Drug Interactions of Artemisinin-Based Combination Therapies in Malaria Treatment: A Narrative Review of the Literature.

Artemisinin is an antimalarial compound derived from the plant Artemisia annua L., also known as sweet wormwood. According to the World Health Organization, artemisinin-based combination therapy (ACT) is an essential treatment for malaria, specifically Plasmodium falciparum, which accounts for most malaria-related mortality. ACTs used to treat uncomplicated malaria include artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, artesunate-sulphadoxine-pyrimethamine, and dihydroartemisinin-piperaquine. Although the mechanism of action and clinical capabilities of artemisinin in malaria treatment are widely known, more information on the potential for drug interactions needs to be further investigated. Some studies show pharmacokinetic and pharmacodynamic drug interactions with HIV antiviral treatment but few studies have been conducted on most other drug classes. Based on known genotypes of cytochrome P450 (CYP) enzymes, CYP2B6 and CYP3A are primarily involved in the metabolism of artemisinin and its derivatives. Reduced functions in these enzymes can lead to subtherapeutic concentrations of the active metabolite, dihydroartemisinin, that may cause treatment failure, which has been shown in some studies with cardiovascular, antibiotic, and antiparasitic drugs. Although the clinical importance remains unclear to date, clinicians should be aware of potential drug-drug interactions and monitor patients on ACT closely.

The Use of Kratom (Mitragyna speciosa Korth.) Among People Who Co-use Heroin and Methamphetamine in Malaysia.

OBJECTIVES: Kratom (Mitragyna speciosa Korth.), an indigenous medicinal plant, has been widely used as a traditional remedy in Southeast Asia. However, its combined consumption with other substances has received scarce attention. This study investigates the use of kratom among adults with a history of using heroin and methamphetamine in Malaysia. METHODS: A total of 332 patients who were mandated to undergo drug rehabilitation participated in this cross-sectional study. The study data were collected through face-to-face interviews using a semi-structured questionnaire. RESULTS: The majority were males (95%, n = 314/332) and Malays (98%, n = 325/332) with a mean age of 32.3 years (SD = 9.16). Over two thirds of the respondents used kratom to alleviate heroin withdrawal symptoms and to reduce methamphetamine intake; 59% used it as a substitute for heroin and methamphetamine. A similar proportion used kratom to reduce heroin intake (58%), while only 15% used it for its euphoric effects. Multivariate analysis showed that previous attendees of government rehabilitation programs had lower odds of using kratom as a heroin substitute. CONCLUSIONS: The potential of kratom to alleviate heroin withdrawal symptoms, and to reduce methamphetamine and heroin intake, among people who co-use heroin and methamphetamine warrants further research.

Glycyrrhizin as a Potential Treatment for the Novel Coronavirus (COVID-19).

COVID-19 is an emerging viral infection of zoonotic origin that is closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused an outbreak in 2003. Therefore, scientists named the new virus SARS-CoV-2. On March 11, 2020, The World Health Organization (WHO) recognized COVID-19 as a global pandemic. At present, three vaccines have been approved or are being considered for approval by national regulatory agencies to immunize against COVID- 19. However, the vaccines do not remain widely available, and no specific treatment against the virus is available. The pathogenesis and proliferation pathways of SARS-CoV-2 are still not well known. Thus, in this article, the saponin glycyrrhizin is discussed as a new potential therapeutic agent of natural origin (licorice root, Glycyrrhiza glabra) for the potential treatment of COVID-19 infections.

Is kratom (Mitragyna speciosa Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls.

OBJECTIVES: Little is known about the cardiotoxic effects of kratom (Mitragyna speciosa Korth.), a medicinal plant. This analytical cross-sectional study investigated the prevalence of electrocardiogram (ECG) abnormalities and QTc intervals in regular kratom users compared with non-kratom-using control subjects. METHODS: We enrolled regular kratom users and non-kratom-using control subjects from three communities. Demographic data, clinical data, kratom use characteristics, and ECG findings were recorded. The mitragynine content of kratom juice was quantified using a validated gas chromatography-mass spectrometry (GC-MS) method. RESULTS: A total of 200 participants (100 kratom users and 100 control subjects) participated in this study. The prevalence of ECG abnormalities in kratom users (28%) did not differ from that of control subjects (32%). Kratom use was not associated with ECG abnormalities, except for significantly higher odds of sinus tachycardia (OR = 8.61, 95% CI = 1.06-70.17, p = 0.035) among kratom users compared with control subjects. The odds of observing borderline QTc intervals were significantly higher for kratom users compared with control subjects, regardless of the age of first use, the duration of use, the daily quantity consumed, and the length of time that had elapsed between last kratom use and ECG assessment. Nevertheless, there were no differences in the odds of having prolonged QTc intervals between kratom users and controls. The estimated average daily intake of mitragynine consumed by kratom users was 434.28 mg. CONCLUSION: We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.

Evaluation of the Mitragynine Content, Levels of Toxic Metals and the Presence of Microbes in Kratom Products Purchased in the Western Suburbs of Chicago.

Kratom (Mitragyna speciosa, Korth) is a tree-like plant that is indigenous to Southeast Asia. Kratom leaf products have been used in traditional folk medicine for their unique combination of stimulant and opioid-like effects. Kratom is being increasingly used in the West for its reputed benefits in the treatment of pain, depression and opioid use disorder. Recently, the United States Food and Drug Administration and Centers for Disease Control have raised concerns regarding the contamination of some kratom products with toxic metals (Pb and Ni) and microbes such as Salmonella. To further explore this issue, eight different kratom products were legally purchased from various "head"/"smoke" shops in the Western Suburbs of Chicago and then tested for microbial burden, a panel of metals (Ni, Pb, Cr, As, Hg, Cd), and levels of the main psychoactive alkaloid mitragynine. All of the samples contained significant, but variable, levels of mitragynine (3.9-62.1 mg/g), indicating that the products were, in fact, derived from kratom. All but two of the samples tested positive for the presence of various microbes including bacteria and fungi. However, none of the samples tested positive for Salmonella. Seven products showed significant levels of Ni (0.73-7.4 µg/g), Pb (0.16-1.6 µg/g) and Cr (0.21-5.7 µg/g) while the other product was negative for metals. These data indicate that many kratom products contain variable levels of mitragynine and can contain significant levels of toxic metals and microbes. These findings highlight the need for more stringent standards for the production and sale of kratom products.

Public Perceptions toward Kratom (Mitragyna Speciosa) Use in Malaysia.

Kratom (Mitragyna speciosa), an indigenous medicinal plant of Southeast Asia, is believed to be harmful. We compared the perceptions toward kratom use among kratom users and non-users in Malaysia. 356 respondents (137 kratom users and 219 non-users) were recruited for this cross-sectional study. The majority of respondents were male (60%, n = 212/356), Malays (88%), and 51% were ≥37 years old. Non-users showed higher unadjusted odds of reporting a perception that kratom use can cause addiction (OR = 6.72, CI: 3.91-11.54, p < .0001), withdrawal symptoms (OR = 7.58, CI: 4.62-12.42, p < .0001), illicit drug use problems (OR = 10.12, CI: 6.14-16.68, p < .0001), impaired social-functioning (OR = 12.05, CI: 7.24-20.05, p < .0001), and health problems (OR = 10.44, CI: 6.32-17.24, p < .0001). Similarly, non-users viewed kratom policies differently from kratom users, displaying increased odds of reporting the belief that kratom use and sales must be regulated with stringent laws (OR = 5.75, CI: 3.61-9.18, p < .0001), and kratom should be regulated instead under the Dangerous Drugs Act 1952 to overcome kratom use problems (OR = 8.26, CI: 4.94-13.82, p < .0001). Because of the disconnect in kratom use perceptions and personal experiences between kratom users and non-users, hastily criminalizing kratom without investigating carefully its scientific merits can significantly impede future kratom research.

The Use of Benzodiazepines among Kratom (Mitragyna Speciosa Korth.) Users.

The leaves from Mitragyna speciosa (Korth.) trees, also known as kratom, are traditionally used in Southeast Asia as a mild psychotropic agent. We investigated the demographic characteristics of persons who used both kratom cocktail and benzodiazepines (BZO) in a sample drawn from a rural area in Penang, Malaysia, and the reasons for BZO use. Seventy-seven participants who currently use a kratom cocktail along with BZO were recruited through snowball sampling for this cross-sectional study. The participants were male, and the majority were Malays (99%, n = 76/77), single (57%, n = 44/77) and employed (91%, n = 70/77). BZO was used with kratom cocktail 1) to increase euphoria; 2) to reduce dependence on methamphetamine; 3) to promote sleep; 4) to ease methamphetamine-associated psychological symptoms and 5) to decrease the craving for kratom. There were no significant differences in the intake of kratom use (p = .751), BZO use duration (p = .259), frequency (p = .188) and quantity (p = .888) of BZO use in the last 7 days, and quantity of BZO use in the last 30 days (p = .337) between kratom users and kratom poly-drug users. An awareness of the health consequences of the co-use of kratom with BZO is needed to prevent untoward health incidents.

Differential response to targeted acupuncture by gender in patients with gastrointestinal cancer cachexia: secondary analysis of a randomized controlled trial.

BACKGROUND: Cancer cachexia (CC) is a significant contributor to mortality and morbidity in patients with gastrointestinal (GI) cancer. Treatment options to prevent or halt the progression of CC are limited. Targeted acupuncture (TA) was used in GI patients with CC to evaluate for a potential gender effect. PATIENTS AND METHODS: Participants (n = 30) were recruited from two outpatient clinics in the northern central part of Florida. All participants were diagnosed with CC and GI cancers. A randomized, single-blind, placebo-controlled clinical trial was used to compare TA to non-targeted acupuncture (NTA) over the course of 8 weeks. Primary endpoints were weight and body composition changes measured by bioelectrical impedance analysis (BIA) and biomarker analysis (tumor necrosis factor (TNF)-α and leptin). Herein, gender differences across and within TA and NTA groups were examined as a secondary analysis. RESULTS: A significant (p = 0.026) interaction between weight and gender was noted, which manifested in a non-significant increase in the male intervention (MI) group, while TNF-α levels significantly increased by gender (p = 0.028) and group (p = 0.006) over the course of the study. All other groups either lost or did not change weight. The extracellular-to-intracellular water (ECW/ICW) ratio was significantly elevated for the TA group (p = 0.02) and for males (p = 0.009) at completion of the study. TNF-α and leptin levels were positively correlated within the MI group at the end of the study. CONCLUSION: A decrease in leptin in the MI group corresponded to higher appetite and weight gain. The elevated ECW/ICW ratio indicates an inflammatory response in the MI group. This gender-specific response may be based on hormone-specific regulation of food intake. Further studies with larger sample sizes are required to support the results.

Self-Report Data on Regular Consumption of Illicit Drugs and HIV Risk Behaviors after Kratom (Mitragyna Speciosa korth.) Initiation among Illicit Drug Users in Malaysia.

This study sought to determine the relationship between kratom (Mitragyna speciosa) initiation and regular consumption of illicit drugs and HIV risk behaviors in a cohort of illicit drug users in Malaysia. 260 illicit drug users with current kratom use were recruited through convenience sampling for this cross-sectional study. All were male, with the majority being Malays (95%, n = 246/260). Results suggest that kratom initiation was associated with significant decrease in the regular use of heroin (odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.40- 0.72; p = .0001), methamphetamine (OR = 0.23, CI: 0.16- 0.35; p < .0001), and amphetamine (OR = 0.17, CI: 0.09- 0.34; p < .0001). Kratom initiation was also associated with reduction in regular HIV risk behaviors such as having sex with sex workers (OR = 0.20, CI: 0.12-0.32; p < .0001), using drugs before sexual intercourse (OR = 0.20, CI: 0.13- 0.31; p < .0001), injecting behaviors (OR = 0.10, CI: 0.04- 0.25; p < .0001), sharing of injection equipment (OR = 0.13, CI: 0.04- 0.43; p < .0001), and injecting with other injection drug users (IDUs) (OR = 0.07, CI: 0.02- 0.24; p < .0001).

Risk of death associated with kratom use compared to opioids.

Kratom use appears to be increasing across the United States, increasing attention to deaths in which kratom use was detected. Most such deaths have been ascribed to fentanyl, heroin, benzodiazepines, prescription opioids, cocaine and other causes (e.g., homicide, suicide and various preexisting diseases). Because kratom has certain opioid-like effects (e.g., pain relief), and is used by some people as a substitute for opioids for pain or addiction, kratom has been compared to "narcotic-like opioids" (e.g., morphine) with respect to risk of death despite evidence that its primary alkaloid, mitragynine, carries little of the signature respiratory depressing effects of morphine-like opioids. This commentary summarizes animal toxicology data, surveys and mortality data associated with opioids and kratom to provide a basis for estimating relative mortality risk. Population-level mortality estimates attributed to opioids as compared to kratom, and the per user mortality risks of opioids as compared to kratom are provided. By any of our assessments, it appears that the risk of overdose death is >1000 times greater for opioids than for kratom. The limitations of the mortality risk estimate warrants caution in individuals with unknown factors such as use of other substances and medications, or other preexisting conditions. More research on kratom safety and risks is needed, as is regulation of commercial kratom products to ensure that consumers are informed by FDA labeling and that kratom products are not contaminated or adulterated with other substances.

Current perspectives on the impact of Kratom use.

The leaves from the tree Mitragyna speciosa, commonly known as Kratom, in the coffee plant family (Rubiaceae) are commonly used in their native habitat of Southeast Asia as a stimulant to sustain energy during hard day labor and as an opioid-like analgesic and sedative. Traditional and modern uses overlap based on the effects of the leaf extract which has also gained popularity in the United States and Europe in the last two decades. Kratom has and is being used for the mitigation of opioid withdrawal symptoms and as a harm reduction agent with a minority of users subsequently developing a dependence on the extract. The respective demographic use patterns of Kratom differ between Southeast Asia and the Western world. While pure Kratom is primarily used by day laborers and misused in conjunction with cough medicine by youth in Southeast Asia, a majority of users in the United States is middle-aged, has at least middle income, private health insurance, and completed some college. Deaths attributed to the use of Kratom have been reported in Europe and the United States but not in Southeast Asia. Although Kratom was detected as the alkaloid mitragynine in the blood of the decedents, causality could not be established in almost all cases because of poly-drug exposures. It is notable that Kratom can cause herb-drug interactions, especially with other central nervous system -active substances. Given the mostly unregulated market for Kratom products in Western countries, consumers may be exposed to adulterated or contaminated products, especially if purchased through websites or the darknet. A number of countries have scheduled Kratom because of its stimulant- and opioid-like effects and the established interaction of the alkaloid mitragynine with opioid receptors.