Continued Risk of Dietary Supplements Adulterated With Approved and Unapproved Drugs: Assessment of the US Food and Drug Administration's Tainted Supplements Database 2007 Through 2021.

The US Food and Drug Administration created the Tainted Dietary Supplement Database in 2007 to identify dietary supplements adulterated with active pharmaceutical ingredients (APIs). This article compares the determination of API adulteration in dietary supplements from the 10-year time period of 2007 through 2016 to the most recent 5-year period of 2017 through 2021. From 2007 through 2021, 1068 unique products were found to be adulterated with APIs. Sexual enhancement and weight loss dietary supplements are the most common products adulterated with APIs. Phosphodiesterase-5 inhibitors are commonly included in sexual enhancement dietary supplements and a single product can include up to 5 APIs. Sibutramine, a drug removed from the market due to cardiovascular adverse events, is the most included adulterant API in weight loss products, although sibutramine analogues, phenolphthalein (which was removed from the US market because of cancer risk), and fluoxetine were also included. While muscle-building dietary supplements were commonly adulterated before 2016, since 2017 no additional adulterated products have been identified. The lack of disclosure of APIs in dietary supplements, circumventing the normal procedure with clinician oversight of prescription drug use, and the use of APIs that are banned by the Food and Drug Administration or used in combinations that were never studied are important health risks for consumers.

Lead in Mineral or Multivitamin-Multimineral Products.

OBJECTIVE: Assess the current daily interim reference level of lead and the amount contained in current mineral and multivitamin-multimineral (MVM) products. DATA SOURCES: PubMed search from 1980 to May 15, 2021, limited to the English language, via the search strategy ((mineral OR multivitamin OR calcium OR iron OR magnesium OR copper OR zinc OR chromium OR selenium) AND (heavy metals OR Pb OR lead)). STUDY SELECTION AND DATA EXTRACTION: Narrative review of studies assessing lead content in mineral or MVM products. DATA SYNTHESIS: Products containing different calcium forms (dolomite, bone meal, natural carbonate) have historically had higher lead levels than others (refined carbonate, lactate, gluconate, acetate, sevelamer), but the gap has closed considerably since the year 2000. Although only limited assessments of magnesium and zinc supplements have been conducted, no alarming average lead amounts were found. MVM products assessed since 2007 had low median or mean lead concentrations. However, large interproduct differences exist, with many products having very little lead and some products having concerning amounts. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: It is difficult for pharmacists and consumers to know the amount of lead in an actual product unless it is tested in an independent third-party lab. The United States Pharmacopeia and NSF International will provide a seal on the products stating that the products have a low level of lead, but even so, children could receive more lead than the Food and Drug Administration's Interim Reference Level. CONCLUSIONS: The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid.

Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank.

There are many nonopioid central nervous system depressant substances that share a gamma-aminobutyric acid (GABA) receptor-related mechanism of action. These sedatives-hypnotics can be indicated to treat anxiety, seizures, depression, and insomnia but are also used as substances of abuse and used to facilitate sexual assault. Barbiturates, methaqualone, and glutethimide were among the first type A GABA receptor-mediated sedative-hypnotics. Their clinical use was limited for most indications by serious adverse events and strong abuse potential but continue to be used illicitly around the world. The benzodiazepines supplanted barbiturates for most indications because they were less likely to cause severe adverse events in monotherapy. Flunitrazepam is a newer benzodiazepine that is preferentially used recreationally and to facilitate sexual assault. Flunitrazepam has greater potency and higher affinity for the type A GABA receptor than most benzodiazepines. Gamma-hydroxybutyric acid is sought illicitly for its hypnotic, euphoric and anabolic effects as well as to facilitate sexual assault. When any of these GABAergic drugs are used in high doses or with other sedative hypnotic agents, respiratory depression, coma, and death have occurred. Chronic use of these GABAergic drugs can lead to significant withdrawal syndromes. Phenibut and selank are poorly studied Russian drugs with GABAergic mechanisms that are inexplicably sold to US consumers as dietary supplements. Poison control center calls regarding phenibut have increased substantially over the past 5 years. Desired euphoriant effects account for the recreational and illicit use of many GABA-modulating agents. However, illicit use can lead to significant toxicities related to abuse, dependence, and subsequent withdrawal syndromes. Significant evaluation of developing agents with GABA properties should be conducted to determine abuse potential before public access ensues.

Dietary Supplements Pose Real Dangers to Patients.

The Dietary Supplement Health and Education Act led to a flood of poor-quality dietary supplements. The Food and Drug Administration's (FDA's) jurisdiction is limited to removing products proven unsafe, rather than prospectively assessing them for quality manufacturing. With so many products available, there is very little FDA oversight until reports of patient harm occur. Microbial and heavy metal contamination, adulteration with synthetic drugs (including drugs banned from the United States), substituting herbs, and fraudulently specifying ingredients on the label have all occurred. Clinicians should collectively advocate for legislative change, only recommend products tested by outside laboratories for quality, and educate consumers about the risks of using unverified products.

Oral turmeric/curcumin effects on inflammatory markers in chronic inflammatory diseases: A systematic review and meta-analysis of randomized controlled trials.

Turmeric extract or active component curcumin may have anti-inflammatory effects in people with chronic inflammatory diseases. The effect of turmeric or curcumin on a wide range of inflammatory markers has not been evaluated in a systematic review. We performed a systematic review of randomized controlled trials (RCTs) evaluating the effects of oral turmeric or curcumin on inflammatory markers (CRP, hsCRP, IL-1, IL-6, TNF) in patients with a wide range of chronic inflammatory diseases. Pubmed, EMBASE, Scopus, the Web of Science, and the Cochrane library were evaluated until June 2018. Random effects meta-analyses with inverse variance methods and stratified by turmeric or curcumin were performed. Effects were expressed as mean differences (MD) and their 95% confidence intervals (CI). Risk of bias of RCTs was evaluated with the Cochrane tool. Nineteen RCTs were identified; included patients had rheumatic diseases, advanced chronic kidney disease with hemodialysis, metabolic syndrome, and cardiovascular diseases. Turmeric was the intervention in 5 RCTs (n = 356) and curcumin/curcuminoids in 14 RCTs (n = 988). Follow up times ranged between 4 and 16 weeks. One RCT had high risk of bias. In comparison to controls, turmeric or curcumin did not significantly decrease levels of CRP (MD -2.71 mg/L, 95%CI -5.73 to 0.31, p = 0.08, 5 studies), hsCRP (MD -1.44 mg/L, 95%CI -2.94 to 0.06, p = 0.06, 6 studies), IL-1 beta (MD -4.25 pg/mL, 95%CI -13.32 to 4.82, p = 0.36, 2 studies), IL-6 (MD -0.71 pg/mL, 95%CI -1.68 to 0.25, p = 0.15), and TNF alpha (MD -1.23 pg/mL, 95%CI -3.01 to 0.55, p = 0.18, 7 studies). There were no differences between turmeric and curcumin interventions. High heterogeneity of effects was observed for all markers across studies, except hsCRP. Other inflammatory markers such as IL-1 alpha, TNF beta, IL-17, and IL-22 had scarce data. Turmeric or curcumin did not decrease several inflammatory markers in patients with chronic inflammatory diseases.

A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential.

Cannabidiol (CBD) is a highly touted product for many different disorders among the lay press. Numerous CBD products are available, ranging from a US Food and Drug Administration (FDA)-approved product called Epidiolex to products created for medical marijuana dispensaries and products sold in smoke shops, convenience stores, and over the Internet. The legal status of the non-FDA-approved products differs depending on the source of the CBD and the state, while the consistency and quality of the non-FDA-approved products vary markedly. Without independent laboratory verification, it is impossible to know whether the labeled CBD dosage in non-FDA-approved CBD products is correct, that the delta-9-tetrahydrocannabinol content is <0.3%, and that it is free of adulteration and contamination. On the Internet, CBD has been touted for many ailments for which it has not been studied, and in those diseases with evaluable human data, it generally has weak or very weak evidence. The control of refractory seizures is a clear exception, with strong evidence of CBD's benefit. Acute CBD dosing before anxiety-provoking events like public speaking and the chronic use of CBD in schizophrenia are promising but not proven. CBD is not risk free, with adverse events (primarily somnolence and gastrointestinal in nature) and drug interactions. CBD has been shown to increase liver function tests and needs further study to assess its impact on suicidal ideation.

Curcumin, a turmeric extract, for oral lichen planus: A systematic review.

OBJECTIVE: Conduct a PROSPERO registered (CRD42018105227) systematic review of the efficacy of curcumin in the treatment of oral lichen planus (OLP). DATA SOURCES: Medline from the earliest possible date to the present (December 18, 2018) using the terms "turmeric" OR "curcumin" OR "curcuma" AND "oral lichen planus". STUDY SELECTION AND DATA EXTRACTION: Studies assessing patient outcomes in OLP. There were four trials assessing the comparative efficacy of topical curcumin vs. topical corticosteroids and three trials assessing the efficacy of oral curcumin vs. placebo. DATA SYNTHESIS: Clinical and methodological heterogeneity precluded statistical pooling. There were many limitations in the literature weakening the strength and applicability of evidence. Topical curcumin provided reductions in pain, burning, and clinical manifestations of OLP versus baseline, effects similar or inferior to topical corticosteroids. In oral curcumin trials, there were no significant benefits of curcumin therapy versus placebo but there were some potential benefits and reasonable safety in an observational extension study. CONCLUSIONS: It is difficult to determine whether topical or oral curcumin is a viable therapy for oral lichen planus. Topically applied curcumin in particular shows promising preliminary data but would likely not supplant topical corticosteroids as the modality of choice for most patients.

Effects of intermittent versus continuous dieting on weight and body composition in obese and overweight people: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Intermittent dieting may be an alternative to continuous dieting for weight reduction. OBJECTIVE: To evaluate the effect of intermittent dieting versus continuous dieting on weight and body composition in overweight or obese adults. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). Five databases were searched until February 2018 for RCTs comparing intermittent versus continuous dieting. Intermittent dieting consisted of two types: regular intermittent was caloric restriction interspersed with days of weight maintenance or ad libitum eating; intensified intermittent was caloric restriction interspersed with days of even lower caloric restriction. Continuous was continual caloric restriction. Primary outcomes were weight, body fat, lean mass, waist circumference, hip circumference, and energy expenditure. Data were pooled by the inverse variance method using random-effects models and expressed as mean differences (MD) and their 95% confidence intervals (CI). RESULTS: Nine trials met the inclusion criteria (n = 782), six comparing regular intermittent vs continuous (n = 553), and three comparing intensified intermittent vs continuous (n = 229). Populations were heterogeneous: obese only in five studies, and overweight or obese (mixed) in four studies. Lean mass was significantly lower in regular intermittent vs continuous (MD -0.86 kg; 95% CI -1.62 to -0.10; p = 0.03). No differences were found for the remaining outcomes for both comparisons (regular intermittent or intensified intermittent vs continuous). There was low heterogeneity of effects across trials. Subgroup effects by time to follow-up, gender, per-protocol versus intention-to-treat, enforced exercise, and diabetes were similar to main analyses. CONCLUSIONS: This systematic review in obese and overweight individuals showed that regular intermittent dieting decreased lean mass compared to continuous dieting. There were no differences in effects for either intermittent vs continuous interventions across all other outcomes. In contrast to previous systematic reviews, this study suggested that lean mass is better preserved in continuous dieting compared to regular intermittent dieting.

Creatine supplementation does not alter the creatine kinase response to eccentric exercise in healthy adults on atorvastatin.

BACKGROUND: Serum creatine kinase (CK) levels are higher after eccentric, muscle-damaging exercise in statin-treated patients. This could contribute to the increased statin-associated muscle symptoms reported in physically active individuals. OBJECTIVE: We tested the hypothesis in this pilot study that creatine (Cr) monohydrate supplementation would reduce the CK response to eccentric exercise in patients using statins to determine if Cr supplementation could be a strategy to mitigate statin-associated muscle symptoms in physically active individuals. METHODS: Healthy, nonsmoking men (n = 5) and women (n = 14) were randomized to Cr monohydrate = atorvastatin 80 mg + 10 g Cr monohydrate (n = 10, age = 60 ± 7 years) or to placebo (PL) = atorvastatin 80 mg + PL (n = 9, age = 52 ± 6 years). After 4 weeks of treatment, subjects performed 45 minutes of eccentric exercise (downhill walking at a -15% grade). Serum CK levels, muscle soreness (visual analog scale after two squats), and muscle pain severity and interference (using the brief pain inventory) were measured before and after 4 weeks of treatment, and then for 4 consecutive days after downhill walking. Vitamin D, or serum 25(OH)D, was also measured at baseline. RESULTS: The PL group was younger (P = .01) but not otherwise different in blood lipids, vitamin D, CK, muscle visual analog scale, and pain scores before (all P > .21) or after (all P > .12) treatment. CK increased in all subjects after downhill walking (P < .01), but neither the relative peak change (expressed as group mean difference with 95% confidence intervals: 43.52% [-196.41, 283.45]) nor the absolute peak change (67.38 U/L [-121.55, 256.31]) relative to baseline was different between groups (P = .46 and .71, respectively). A similar lack of treatment effect was observed for muscle soreness (11.03 mm [-9.49, 31.55]), pain severity (0.77 pts [-0.95, 2.50]), and pain interference (1.02 pts [-1.25, 3.29]) with P-values for group comparisons = 0.27, 0.36, and 0.35, respectively. However, subjects with "insufficient" Vitamin D < 30 ng/mL (n = 10) had an ∼2-fold greater CK increase with eccentric exercise (nominal P-value = .04) than subjects with higher vitamin D levels. CONCLUSION: Cr monohydrate did not reduce CK increases after exercise in statin-treated subjects. We did observe that low vitamin D levels are associated with a greater CK response to eccentric exercise in statin-treated subjects.

The Pharmacology, Pharmacokinetics, Efficacy, and Adverse Events Associated With Kava.

Kava is a plant with numerous kavapyrones that can induce pharmacologic effects and drug interactions through the cytochrome P450 and P-glycoprotein systems. Kava is used recreationally and for the treatment of anxiety. Clinical trials verify anxiolytic effects in excess of placebo, but the effects are not seen immediately and the optimal dose and dosing schedule needs to be determined. Clinical trials usually lasting for 4 weeks found generally good tolerability and safety; however, dermatologic, hepatologic, and cognitive adverse effects may occur. Some of these adverse effects are known to occur from the kavapyrones themselves, while others can be caused or exacerbated by use of substandard kava products. There is tremendous variability in the constitution of a kava product based on the parts of the plant that are being extracted and the extraction method. The most commonly studied extract for the treatment of anxiety is the acetone extract.

The effect of high-dose atorvastatin on neural activity and cognitive function.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks. METHODS: Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions. RESULTS: There were few changes in standard neuropsychological tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color-Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P<.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.

Rates of major bleeding with rivaroxaban in real-world studies of nonvalvular atrial fibrillation patients: a meta-analysis.

Numerous real-world studies estimating major bleeding rates in rivaroxaban patients with nonvalvular atrial fibrillation have been published. We performed a meta-analysis to better quantify the rates of different types of major bleeding seen with rivaroxaban in observational studies. The pooled rates of major bleeding with rivaroxaban were generally low and consistent with those reported in its pivotal randomized controlled trial.

A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.

BACKGROUND: Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. OBJECTIVE: This study examined the effect of coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. METHODS: Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. RESULTS: Serum CoQ10 increased from 1.3 ± 0.4 to 5.2 ± 2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3 ± 0.3 to 0.8 ± 0.2) (p < 0.05). BPI pain severity and interference scores increased with simvastatin therapy (both p < 0.01), irrespective of CoQ10 assignment (p = 0.53 and 0.56). There were no changes in muscle strength or VO2max with simvastatin with or without CoQ10 (all p > 0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p = 0.05). There was no difference in time to pain onset in the CoQ10 (3.0 ± 2.0 weeks) vs. placebo (2.4 ± 2.1 wks) groups (p = 0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. CONCLUSIONS: Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial RegistrationNCT01140308; www.clinicaltrials.gov.

Increases in creatine kinase with atorvastatin treatment are not associated with decreases in muscular performance.

BACKGROUND: The present study examined if increases in creatine kinase (CK) levels during high-dose atorvastatin treatment are associated with changes in skeletal muscle function and symptoms. METHODS: The Effect of Statins on Muscle Performance study (STOMP) investigated the effects of atorvastatin 80 mg daily for 6 months on muscle performance, exercise capacity, and the incidence of statin-associated muscle complaints in healthy adults. RESULTS: CK levels increased with atorvastatin (n = 202) from 132.3 ± 120.9 U/L (mean ± SD) at baseline to 159.7 ± 170.4 and 153.1 ± 139.4 U/L at 3 and 6 months, respectively (P ≤ 0.002 for both). Changes in CK with atorvastatin treatment were not associated with changes in muscle function or the incidence of myalgia. More subjects on atorvastatin (n = 24) compared to placebo (n = 12 of 217) doubled their CK level at 6 months (P = 0.02). No differences in muscle function or physical activity were observed between atorvastatin-treated subjects who did or did not double their CK. CONCLUSIONS: Results of the present investigation extend the findings of STOMP by demonstrating that greater increases in CK levels with high-dose atorvastatin treatment did not deleteriously impact skeletal muscle function or predict skeletal muscle complaints. This study was registered at ClinicalTrials.gov (NCT00609063).

A randomized trial of coenzyme Q10 in patients with statin myopathy: rationale and study design.

BACKGROUND: Statins are the most commonly prescribed and effective medications for reducing low-density lipoprotein levels. Some patients experience myopathic symptoms during statin treatment. The etiology is not known, but depletion of mevalonate pathway metabolites, including coenzyme Q10 (CoQ10), has been suggested. Despite a lack of conclusive evidence supporting its utility, CoQ10 supplementation has been recommended to patients who experience myalgic symptoms. OBJECTIVE: The Co-Enzyme Q10 in Statin Myopathy study is designed to examine the effect of CoQ10 supplementation on the extent and intensity of muscle pain during treatment with simvastatin. METHODS: We will recruit patients with a documented history of myalgia during statin treatment. The presence of statin-related myalgia will be confirmed in a crossover run-in trial during which the presence and absence of symptoms will be documented during statin and placebo treatment, respectively. Individuals experience myalgic symptoms while taking statins but not placebo will be randomized to receive simvastatin 20 mg daily plus either 600 mg daily of CoQ10 or placebo. Muscle pain intensity will be documented during weekly phone calls via use of the Brief Pain Inventory, Short Form. Treatment will continue for 8 weeks or until muscle symptoms are reported continuously for 1 week or become intolerable, and then subjects will crossover to the alternative treatment (CoQ10 or placebo). RESULTS: This study is an ongoing clinical trial. CONCLUSIONS: This study will determine the utility of CoQ10 for reducing pain intensity in myalgic patients and will provide guidance for clinicians treating patients with hypercholesterolemia who are intolerant to statins.

Effect of statins on skeletal muscle function.

BACKGROUND: Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. METHODS AND RESULTS: The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). CONCLUSIONS: These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

Improved glucose control associated with i.v. chromium administration in two patients receiving enteral nutrition.

PURPOSE: The effect of i.v. chromium administration on glucose control in two patients receiving enteral nutrition is described. SUMMARY: Chromium supplementation has been hypothesized to potentiate the actions of insulin in facilitating cellular uptake of glucose. We report two cases-one involving a diabetic patient and the other a nondiabetic patient-in which chromium administration appeared to decrease insulin requirements. In case 1, a diabetic patient given a single course of chromic chloride appeared to have a probable response to the drug. Within the first day of chromic chloride administration, insulin requirements declined. When chromic chloride was discontinued, insulin requirements did not rise, suggesting efficacy and sustained effect. The patient's glucose intake and blood glucose levels remained relatively stable, while there was a significant decline in insulin requirements. Serum chromium levels were not assessed, so it is uncertain if the patient experienced chromium deficiency or if it was adequately treated with chromium supplementation, and a dose-response relationship could not be ascertained because the patient received a continuous infusion of chromium. In case 2, the insulin requirements of a nondiabetic patient appeared to decrease in response to multiple courses of chromic chloride. Upon initial discontinuation of chromic chloride, the patient's lower insulin requirements were sustained for a few days, but changes in clinical status and other medications precipitated elevated insulin requirements and the need for subsequent chromic chloride administration. Further research in more controlled settings is necessary to elucidate chromium's effect on insulin requirements. CONCLUSION: Infusion of chromic chloride appeared to reduce insulin requirements in one diabetic patient and one nondiabetic patient.

A meta-analysis evaluating the impact of chitosan on serum lipids in hypercholesterolemic patients.

BACKGROUND/OBJECTIVE: Chitosan is increasingly being used in the United States as an over-the-counter cholesterol-lowering agent. The positively charged amino groups of chitosan may have the ability to bind negatively charged molecules such as lipids and bile acids, inducing a greater fractional excretion in the feces. To better characterize the impact of chitosan on serum lipids in hypercholesterolemic patients, we performed a meta-analysis of randomized controlled trials. METHODS: A systematic literature search of Medline, Embase, Cochrane Central and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through May 2008. Trials were included in the analysis if they were randomized, placebo-controlled trials of chitosan in hypercholesterolemic patients and reported efficacy data on total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol or triglycerides. The weighted mean difference (WMD) of the change from baseline (in milligrams per deciliter) with 95% confidence interval was calculated as the difference between the mean in the chitosan and placebo groups using a random-effects model. RESULTS: Six studies (n = 416 patients) met the inclusion criteria. Upon meta-analysis, the use of chitosan significantly lowered total cholesterol [WMD, -11.59 mg/dl (-21.45 to -1.73), p = 0.02] but not LDL cholesterol, HDL cholesterol or triglycerides. CONCLUSIONS: Based upon the currently available literature, we can only say that chitosan beneficially affects total cholesterol with 95% confidence. Additional, larger randomized controlled trials are needed to better characterize the effect of chitosan on other lipoproteins.

The impact of garlic on lipid parameters: a systematic review and meta-analysis.

In order to determine the impact of garlic on total cholesterol (TC), TAG levels, as well as LDL and HDL, and establish if any variables have an impact on the magnitude of this effect, a meta-analysis was conducted. A systematic literature search of MEDLINE, CINAHL and the Cochrane Database from the earliest possible date through to November 2007 was conducted to identify randomised, placebo-controlled trials of garlic that reported effects on TC, TAG concentrations, LDL or HDL. The weighted mean difference of the change from baseline (with 95 % CI) was calculated as the difference between the means in the garlic groups and the control groups using a random-effects model. Subgroup and sensitivity analyses were performed to determine the effects on type, brand and duration of garlic therapy as well as baseline TC and TAG levels, the use of dietary modification, and study quality on the meta-analysis's conclusions. Twenty-nine trials were included in the analysis. Upon meta-analysis garlic was found to significantly reduce TC ( - 0.19; 95 % CI - 0.33, - 0.06 mmol/l) and TAG ( - 0.11; 95 % CI - 0.19, - 0.06 mmol/l) but exhibited no significant effect on LDL or HDL. There was a moderate degree of statistical heterogeneity for the TC and TAG analyses. Garlic reduces TC to a modest extent, an effect driven mostly by the modest reductions in TAG, without appreciable LDL lowering or HDL elevation. Higher baseline line TC levels and the use of dietary modification may alter the effect of garlic on these parameters. Future studies should be conducted evaluating the impact of adjunctive garlic therapy with fibrates or statins on TAG concentrations.