Safety Of Dietary Supplements Research Articles

Efficacy and Safety of Armolipid Plus®: An Updated PRISMA Compliant Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

Armolipid Plus® is a multi-constituent nutraceutical that claims to improve lipid profiles. The aim of this PRISMA compliant systematic review and meta-analysis was to globally evaluate the efficacy and safety of Armolipid Plus® on the basis of the available randomized, blinded, controlled clinical trials (RCTs). A systematic literature search in several databases was conducted in order to identify RCTs assessing the efficacy and safety of dietary supplementation with Armolipid Plus®. Two review authors independently identified 12 eligible studies (1050 included subjects overall) and extracted data on study characteristics, methods, and outcomes. Meta-analysis of the data suggested that dietary supplementation with Armolipid Plus® exerted a significant effect on body mass index (mean difference (MD) = −0.25 kg/m2, p = 0.008) and serum levels of total cholesterol (MD = −25.07 mg/dL, p < 0.001), triglycerides (MD = −11.47 mg/dL, p < 0.001), high-density lipoprotein cholesterol (MD = 1.84 mg/dL, p < 0.001), low-density lipoprotein cholesterol (MD = −26.67 mg/dL, p < 0.001), high sensitivity C reactive protein (hs-CRP, MD = −0.61 mg/L, p = 0.022), and fasting glucose (MD = −3.52 mg/dL, p < 0.001). Armolipid Plus® was well tolerated. This meta-analysis demonstrates that dietary supplementation with Armolipid Plus® is associated with clinically meaningful improvements in serum lipids, glucose, and hs-CRP. These changes are consistent with improved cardiometabolic health.

The Romanian consumers’ perception regarding the safety of dietary supplements

The efficacy and security of food supplements are largely used terms nowadays, giving rise to controversies regarding the safety or risks that may occur in consuming such products. In the international literature, there are studies regarding the consumption of dietary supplements from a medical or sociological point of view. The present study focused on the analysis of the Romanian population’s opinion regarding the safety of dietary supplements (from the consumer protection point of view), also identifying the profile of the Romanian consumers in terms of consuming supplements, the perception of the consumer concerning the safety of these products and the main factors which determine the behaviour of supplements consumers. The background of the study includes a literature review and some controversies regarding how efficient it is to consume food supplements. The classification tree was used as a pertinent, rigorous, structured and easily readable method. A survey was performed among 333 Romanian respondents who belong to different social classes. The present study draws conclusions related to the importance of mass media, friends’ advice and the effects of using dietary supplements in drawing up a clear opinion of the Romanian consumers’ perception regarding the safety of using supplements.

Health Beneficial Effects of Moomiaii in Traditional Medicine.

Traditional medicine (TM) that developed over the years within various societies consists of medical experimental knowledge and practices, which apply natural methods and compounds for general wellness and healing. Moomiaii as a pale-brown to blackish-brown natural exudate is one of the natural compounds in traditional medicine that has been used over 3000 years in many countries of the world especially in India, China, Russia, Iran, Mongolia, Kazakhstan and Kirgizstan. We reviewed all English-language studies about Moomiaii that we accessed them. In traditional medicine, many beneficial activities have been attributed to Moomiaii and to its main constituents, Humic acid and Fulvic acid, which are widely used to prevent and treatment of different diseases. Some modern scientific investigations showed that Moomiaii as a safe dietary supplement can be beneficial in various health complications. Even though the beneficial effects of Moomiaii have been confirmed in traditional and modern medicine, it seems that additional in-vitro/in-vivo studies and comprehensive clinical trials are necessary to explain the whole mechanisms of action and to determine the effective doses in various diseases. We discuss and clarify the claimed health beneficial effects of Moomiaii in some wide-spread diseases regarding its anti-ulcerogenic, immunomodulatory, antidiabetic, antioxidative and anticancer properties.

Health Beneficial Effects of Moomiaii in Traditional Medicine

raditional medicine (TM) that developed over the years within various societies consists of medical experimental knowledge and practices, which apply natural methods and compounds for general wellness and healing. Moomiaii as a pale-brown to blackish-brown natural exudate is one of the natural compounds in traditional medicine that has been used over 3000 years in many countries of the world especially in India, China, Russia, Iran, Mongolia, Kazakhstan and Kirgizstan. We reviewed all English-language studies about Moomiaii that we accessed them. In traditional medicine, many beneficial activities have been attributed to Moomiaii and to its main constituents, Humic acid and Fulvic acid, which are widely used to prevent and treatment of different diseases. Some modern scientific investigations showed that Moomiaii as a safe dietary supplement can be beneficial in various health complications. Even though the beneficial effects of Moomiaii have been confirmed in traditional and modern medicine, it seems that additional in-vitro/in-vivo studies and comprehensive clinical trials are necessary to explain the whole mechanisms of action and to determine the effective doses in various diseases. We discuss and clarify the claimed health beneficial effects of Moomiaii in some wide-spread diseases regarding its anti-ulcerogenic, immunomodulatory, antidiabetic, antioxidative and anticancer properties. [GMJ.2020;9:e1743]

Incorporation of in vitro techniques for botanicals dietary supplement safety assessment – Towards evaluation of developmental and reproductive toxicity (DART)

As complex mixtures, botanicals present unique challenges when assessing safe use, particularly when endpoint gaps exist that cannot be fully resolved by existing toxicological literature. Here we explore in vitro gene expression as well receptor binding and enzyme activity as alternative assays to inform on developmental and reproductive toxicity (DART) relevant modes of action, since DART data gaps are common for botanicals. Specifically, botanicals suspected to have DART effects, in addition to those with a significant history of use, were tested in these assays. Gene expression changes in a number of different cell types were analysed using the connectivity mapping approach (CMap) to identify modes of action through a functional read across approach. Taken together with ligand affinity data obtained using a set of molecular targets customised towards known DART relevant modes of action, it was possible to inform DART risk using functional analogues, potency comparisons and a margin of internal exposure approach.

Opportunity of using dietary supplements, control of blood pressure as a complex treatment of arterial hypertension

The article presents the results of a research of evaluation of the effectiveness and safety of dietary supplements and control of blood pressure as a complex treatment in patients with the 1st and 2nd stages of arterial hypertension (AH). It was found that using the complex product blood pressure control stabilises systolic and diastolic blood pressure.

Safety of dietary supplements use among patients with cancer: A systematic review.

Dietary supplements (DS) are commonly taken by patients with cancer, but safety of DS use remains unclear. A systematic literature search was conducted using PubMed, ClinicalTrials.gov, International Pharmaceutical Abstracts and Alt HealthWatch databases from inception through October 12, 2018. Included studies were limited to clinical trials including patients with cancer, DS products as interventions, evaluation of safety endpoints of DS use, and published in English. Sixty-five studies were included to evaluate 20 different DS among patients with 12 types of cancer. Botanical DS (n = 13), vitamins (n = 8), and probiotics/synbiotics (n = 7) were the top 3 types of DS evaluated in these trials. Majority of studied DS appeared safe. Among 19 trials including patients with cancer undergoing chemotherapy, most (n = 18) of studied DS (e.g., vitamins, botanical, omega-3 fatty acid) were found to be safe. Evaluation of DS use and its safety should be regularly incorporated in clinical trials among patients with cancer.

Dietary supplements for prediabetes: A protocol for a systematic review and meta-analysis.

The number of prediabetic individuals is at a high level worldwide and they have an increased risk of developing diabetes, causing severe physical impairment and heavy financial burden. Recently, using various dietary supplements is increasingly common, and relevant trials of different diseases are increasing correspondingly. The effects of dietary supplements have been confirmed in some studies among prediabetic individuals. However, there remains no comprehensive systematic review to assess the efficacy and safety of dietary supplements intake in prediabetic individuals. We plan to search and retrieve applicable randomized controlled trials of dietary supplements for prediabetic individuals in the following databases before June 2020: PubMed, Web of Science, EMBASE, the Cochrane Library, the Cochrane Central Register of Controlled Trials(CENTRAL), Allied and Complementary Medicine Database(AMED), Chinese Biomedical Literature database, Wan Fang database, Chinese Scientific Journal database (VIP), Chinese National Knowledge Infrastructure database(CNKI), and the ClinicalTrials.gov website. Two reviewers will separately perform study selection, data extraction, methodological quality assessment and quality of evidence assessment. Data analysis and publication bias will be conducted by Review Manager 5.3. This evidence-based medicine systematic review will prove the efficacy and safety of multifarious dietary supplements for prediabetes. As this systematic review is based merely on already published literature, no approval of the ethics committee is required. We will disseminate this systematic review to a peer-reviewed journal. INPLASY202040057.

Naringenin Attenuates Toxicity and Oxidative Stress Induced by Lambda-cyhalothrin in Liver of Male Rats.

Extensive use of Lambda-cyhalothrin (LTC), a synthetic pyrethroid insecticide, has been associated with serious health problems to the non-target organisms including mammals. The present study investigated the protective effect of naringenin (NGN), an antioxidant flavonoid, against the toxicity induced LTC in the liver of male rats. Five groups of rats were assigned as follows; control group, LTC group (6.12 mg kg-1, 1/10 LD50), LTC-NGN group (6.12 mg kg-1 LTC and 50 mg kg-1 NGN), NGN-LTC group (50 mg kg-1 NGN and 6.12 mg kg-1 LTC) and NGN group (50 mg kg-1). Doses were administrated orally for 21 consecutive days. Administration of LTC induced liver damage as indicated by the increase in the activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase and in the level of total bilirubin in serum. LTC also induced a significant elevation in the levels of serum total lipids, total cholesterol, triglycerides and low-density lipoproteins while high-density lipoproteins decreased. Furthermore, LTC significantly disturbed the oxidant/antioxidant balance in the liver as shown by the elevation in lipid peroxidation, lipid hydroperoxides, protein carbonyl content and conjugated dienes with a concomitant inhibition in the major antioxidants such as reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase. Both post-treatment and pre-treatment with NGN significantly modulated the LTC-induced hepatotoxicity and oxidative stress in rat's liver and pretreatment was found to be more effective in improving most of the studied parameters in both serum and liver tissue. NGN could be used as a safe dietary supplement to protect against the toxicity and oxidative stress associated with the use of LTC.

Toxicity of Herbs, Vitamins, and Supplements.

In the United States, the Food and Drug Administration regulates the efficacy and safety of pharmaceutical drugs. This government agency was formed in direct response to a mass poisoning and more than 100 deaths from kidney failure due to a medicinal toxic alcohol exposure. In contrast, the Food and Drug Administration also regulates the use of vitamins, minerals, herbs, or botanicals as dietary supplements, banning specific medical claims but requiring no documentation of efficacy. Safety of dietary supplements is only ensured through reporting of adverse events and rarely through intervention. Consumers should be aware that supplements may in fact contain actual pharmaceuticals or nothing of value and have significant toxic potential. Toxicity due to Chinese herbal medicines, aristolochic acid, amygdalin, hypervitaminosis D, and heavy metal contamination is reviewed.

In vitro assessment of cytotoxicity and anti-inflammatory properties of shilajit nutraceutical: A preliminary study

Background: Shilajit is a nutraceutical exudate found mainly in the Indian Himalayas, which is formed for centuries by the gradual decomposition of certain plants due to microbial action. It has been effectively used as a potent and safe dietary supplement, restoring the energetic balance and potentially able to prevent several diseases. Hence, the aim of the present preliminary in vitro study is to assess the cytotoxicity of shilajit extract and to comparatively evaluate the anti-inflammatory effect of shilajit and diclofenac sodium, a commonly used drug. Materials and Methodology: Shilajit was commercially procured in pure powder form which was dissolved in 10 ml of methanol and boiled for 80 min, followed by centrifugation (2500 rpm) for 10 min. The supernatant fluid thus obtained was used as an experimental solution. 25-mg diclofenac sodium was used as a control drug. The cytotoxicity of shilajit extract was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas the anti-inflammatory property of the test groups was comparatively evaluated using protein denaturation assay. Results: As the dilution of the extracts increased, the amount of cell viability was also increased, thereby showing that the diluted shilajit extract concentrations proved to be least cytotoxic. Different percentages of shilajit exhibited concentration-dependent inhibition of protein denaturation. Although shilajit extract exerted marginally better anti-inflammatory effect than diclofenac sodium, the effect being dose dependent; the protein inhibition values were not statistically significant (P > 0.05). Conclusion: Within the limitations of this in vitro preliminary study, it can be concluded that: (i) shilajit extract was found to be nontoxic when tested on L929 mouse fibroblast cell lines and (ii) the anti-inflammatory effect of shilajit was comparable to that of diclofenac sodium. Hence, this nutraceutical can be a viable alternative to conventional anti-inflammatory drugs in the field of medicine and dentistry.

Concomitant Use of Dietary Supplements and Medicines among Preschool and School-Aged Children in Japan.

Dietary supplement use is widespread amongst the general population including in children and adolescents. The ingredients in dietary supplements can interact with medicines when patients take them concomitantly. However, the prevalence of the concomitant use of dietary supplements and medicines in Japan among children remains unclear. To clarify this issue, a nationwide internet survey was administered to 55,038 mothers (25 to 60 years old) of preschool- or school-aged children in Japan. Among them, 7.6% currently provide dietary supplements and 3.2% concomitantly provide dietary supplements and prescription or over-the-counter medicines to their children. The prevalence of concomitant use increased with the children’s grade. Among 1057 mothers with 1154 children who were concomitantly using dietary supplements and medicines, 69.1% provided dietary supplements without physician consultation because they considered dietary supplements as only foods and therefore safe. Although the purpose of the use and types of dietary supplement differed between boys and girls, the most popular product was probiotics in both boys and girls. Among concomitant users, 8.3% of mothers gave dietary supplements for treatment of diseases and 4.9% mothers recognized the adverse events of dietary supplements in their child. The findings of this study suggest that mothers’ knowledge about the risk of using dietary supplement with medicines is insufficient. Parental education about the safety of dietary supplements and potential risk of drug–supplement interaction is needed.

Ubiquinol Supplementation Alters Exercise Induced Fatigue by Increasing Lipid Utilization in Mice.

Ubiquinol (QH), a reduced form of coenzyme Q10, is a lipid antioxidant that is hydro-soluble and is commonly formulated in commercial supplements. Ubiquinol has been increasingly reported to exert antioxidant functions, in addition to its role in the cell energy-producing system of mitochondria and adenosine triphosphate (ATP) production. The aim of this study was to assess the potential beneficial effects of QH on anti-fatigue and ergogenic functions following physiological challenge. Forty 8-week-old male Institute of Cancer Research (ICR) mice were divided into four groups (n = 10 for each group): Group 1 (vehicle control or oil only); Group 2 (1X QH dose or 102.5 mg/kg); Group 3 (2X QH dose or 205 mg/kg); Group 4 (6X QH dose or 615 mg/kg). Anti-fatigue activity and exercise performance were studied using the forelimb grip strength experiment and exhaustive weight-loaded swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen), creatine kinase (CK), and free fatty acids (FFA) after an acute exercise challenge. The forelimb grip strength and exhaustive weight-loaded swimming time of the QH-6X group were significantly higher than those of the other groups. QH supplementation dose-dependently reduced serum lactate, ammonia, and CK levels and increased the FFA concentration after acute exercise. In addition, QH increased the liver and muscle glycogen content, an important energy source during exercise. Therefore, the results suggest that QH formulation is a safe dietary supplement for amelioration of fatigue and for promoting exercise performance.

Reversal effects of some safe dietary supplements on lead contaminated diet induced impaired growth and associated parameters in Nile tilapia

This experiment was performed to verify the potential of dietary supplementation with bentonite, mannan-Oligosaccharide (MOS), organic selenium (OS) or vitamin C on reversing the harmful impacts resulting from lead (Pb) diet contamination in Nile tilapia (Oreochromis niloticus). One hundred and eighty tilapia fish were alienated into six groups fed on basal diet only, basal diet polluted with 50 ppm Pb, Pb polluted basal diet supplemented with 40 g bentonite, 50 mg vitamin C, 4 g MOS or 0.3 mg of organic selenium/kg diet for 16 weeks. The results revealed that fish fed diets polluted with Pb showed significantly (P < 0.01) impaired in growth performance indicators, hematological parameters, liver, and kidney by products. In contrast, a significant (P < 0.01) enhancement in the growth performance was noted with the tested feed additives with the highest level in MOS treated group followed by OS then bentonite and vitamin C. Also, fish groups fed diet fortified with the tested feed additives showed a significant (P < 0.05) enhancement in serum albumin, total protein, erythrocytes, and hemoglobin concentrations. Moreover, supplemented the contaminated diets with studied feed additives significantly (P < 0.001) reduces the Pb residuals in the fish body. Conclusively, supplementation of the fish diet with the tested feed additives could be a very useful strategy to combat the hazards of metal toxicity in fish.

HDL Function Dietary Supplement Safety and QOL

HDL Function Dietary Supplement Safety and QOL

Determinants of taking dietary supplements in Iranian children and adolescents: the CASPIAN-V study.

Tendency for taking dietary supplements is dramatically increasing. However, limited studies exist in this regard. We aimed to assess the frequency and determinants of dietary supplement use among a nationally-representative sample of Iranian children and adolescents. This population-based cross-sectional study (the CASPIAN V) was conducted in students aged 7 to 18years old in 2015. Multistage, stratified cluster sampling method was used to select participants from thirty provinces in Iran. Data regarding taking vitamin and mineral supplements were collected. Demographic information, anthropometric indices, physical activity, screen time and body image were also evaluated. Multivariate logistic regression model was used for analyses. The prevalence of dietary supplements use was 34.1% and the most popular dietary supplement was Iron (12.9%). Multivariate logistic regression showed that boys (0.84, 95%CI: 0.78, 0.91) and body image perception (OR: 0.84, 95%CI: 0.75, 0.94) used less dietary supplements compared to others. Children aged 11 to 14years (OR: 1.15, 95%CI: 1.06, 1.26) and those with moderate family socioeconomic status (OR: 1.12, 95%CI: 1.007, 1.25) used more supplement compared to other groups. Moreover, those with higher paternal educational level (OR: 0.77, 95%CI: 0.64, 0.93) used less supplements. However, living area, family size, paternal occupation, children BMI, Intended weight loss, and body image by student did not indicate any significant association. Our findings indicated that about one-third of Iranian children and adolescents used dietary supplements; iron supplements were the most frequent ones. Children aged 11 to 14years, those with higher educated mothers and moderate family socioeconomic status used more supplements compared to others. However, boys, children with excess weight and those with high-educated parents used less supplements compared to others. More studies are needed to clarify the efficacy and safety of dietary supplements in different age groups in various societies.

Chemoprevention of inflammation-related colorectal cancer by silymarin-, acetyl-11-keto-beta-boswellic acid-, curcumin- and maltodextrin-enriched dietetic formulation in animal model.

On the basis of preliminary in vitro experience, we assessed whether an enriched nutritional formulation with estrogen receptor (ER)-beta agonist and anti-inflammatory properties may prevent inflammation-associated colorectal cancer (CRC) in an animal model. Study sample enclosed 110 C57BL/6J male mice. Forty underwent dietary supplement safety assessment (20 standard diet and 20 enriched formulation). Seventy were treated with azoxymethane (AOM)/dextran sulfate sodium and divided into two groups: 35 received standard diet and 35 enriched formulation (curcumin, boswellic acids, silymarin and maltodextrins). Miniature colonoscopy demonstrated colitis and solid lesion development in five mice/group 100 days after first AOM injection. Mice were killed after 10 days. In each group, four subgroups received intraperitoneal bromodeoxyuridine (BrdU) injection at 24th/48th/72nd/96th hour before killing. Anti-inflammatory effect and chemoprevention were evaluated by lesion number/size, histological inflammation/dysplasia/neoplasia assessment, pro-inflammatory cytokine messenger RNA (mRNA), ER-beta/ER-alpha/BrdU immunohistochemistry and TUNEL immunofluorescence. Standard formulation assumption was associated with colon shortening compared with enriched one (P = 0.04), which reduced solid lesion number and size (P < 0.001 for both), histological inflammation score (P = 0.04), pro-inflammatory cytokine mRNA expression (P < 0.001), number of low-grade dysplasia (LGD; P = 0.03) and high-grade dysplasia (P < 0.001) areas. CRC was observed in 69.6% in standard and 23.5% in enriched formulation assuming animals (P < 0.001). Enriched formulation induced lower ER-alpha expression in CRC (P < 0.001) and higher ER-beta expression in LGD (P < 0.001) being associated to higher epithelial turnover (BrdU; P<0.001) in normal mucosa and increased apoptosis in LGD and CRC (P < 0.001 for both). Our results are promising for a successful anti-inflammatory and chemopreventive effect of enriched formulation in CRC arising from inflamed tissue.

Using natural language processing methods to classify use status of dietary supplements in clinical notes

BackgroundDespite widespread use, the safety of dietary supplements is open to doubt due to the fact that they can interact with prescribed medications, leading to dangerous clinical outcomes. Electronic health records (EHRs) provide a potential way for active pharmacovigilance on dietary supplements since a fair amount of dietary supplement information, especially those on use status, can be found in clinical notes. Extracting such information is extremely significant for subsequent supplement safety research.MethodsIn this study, we collected 2500 sentences for 25 commonly used dietary supplements and annotated into four classes: Continuing (C), Discontinued (D), Started (S) and Unclassified (U). Both rule-based and machine learning-based classifiers were developed on the same training set and evaluated using the hold-out test set. The performances of the two classifiers were also compared.ResultsThe rule-based classifier achieved F-measure of 0.90, 0.85, 0.90, and 0.86 in C, D, S, and U status, respectively. The optimal machine learning-based classifier (Maximum Entropy) achieved F-measure of 0.90, 0.92, 0.91 and 0.88 in C, D, S, and U status, respectively. The comparison result shows that the machine learning-based classifier has a better performance, which is more efficient and scalable especially when the sample size doubles.ConclusionsMachine learning-based classifier outperforms rule-based classifier in categorization of the use status of dietary supplements in clinical notes. Future work includes applying deep learning methods and developing a hybrid system to approach use status classification task.

Are dietary supplements dangerous? Assessing how society perceives the usage of dietary supplements – results of the preliminary analysis of nationwide survey data

Background: Dietary supplements (DSs) are concentrated sources of nutrients and/or other substances, whose purpose is to supplement the normal diet. Their consumption in Poland has been on the rise, leading to numerous concerns. However, current legislation does not provide any background for a relevant pharmacovigilance system. Therefore, little is known about their adverse effects (AEs) or patterns of use in Poland. To shed some light on this, we conducted a nationwide survey. Aim of the study: To assess the prevalence of, and the reasons for, the use of dietary supplements in Poland via national survey with a collection and an analyse of supposed adverse effects of dietary supplements. Material and methods: The study was conducted using an online survey based on the original questionnaire. In this report, we present the results of the analysis of the first 200 responses. Results: As many as 55.5% (111) of respondents were ‘definitely sure’ or ‘rather sure’ about DSs safety. However, 70.5% (141) believed that they could have negative effects. Over 3/4 (153) of respondents used DSs themselves, and 61.0% (122) used them within last 12 months. Of those using DSs, 11.1% (17) reported diverse AEs, with GI tract irritation and mental disturbances being the most common (experienced by 35.3% (6), and 17.6% (3) of those reporting AE s, respectively). Conclusions: Respondents had mixed feelings about DS safety. Despite that, they used these products frequently. Of a note is high incidence of adverse effects experienced by DS users. This undoubtedly points to the need for a relevant pharmacovigilance system.

Safety of dietary supplementation with arginine in adult humans.

Previous studies with animals and humans have shown beneficial effects of dietary supplementation with L-arginine (Arg) on reducing white fat and improving health. At present, a long-term safe level of Arg administration to adult humans is unknown. The objective of this study was to conduct a randomized, placebo-controlled, clinical trial to evaluate the safety and tolerability of oral Arg in overweight or obese but otherwise healthy adults with a body mass index of ≥ 25kg/m2. A total of 142 subjects completed a 7-day wash-in period using a 12g Arg/day dose. All the remaining eligible 101 subjects who tolerated the wash-in dose (45 men and 56 women) were assigned randomly to ingest 0, 15 or 30g Arg (as pharmaceutical-grade Arg-HCl) per day for 90days. Arg was taken daily in at least two divided doses by mixing with a flavored beverage. At Days 0 and 90, blood pressures of study subjects were recorded,their physical examinations were performed, andtheirblood and 24-h urine samples were obtained to measure: (1) serum concentrations of amino acids, glucose, fatty acids, and related metabolites; and (2) renal, hepatic, endocrine and metabolic parameters. Our results indicate that the serum concentration of Arg in men or women increased (P < 0.05) progressively with increasing oral Arg doses from 0 to 30g/day. Dietary supplementation with 30g Arg/day reduced (P < 0.05) systolic blood pressure and serum glucose concentration in females, as well as serum concentrations of free fatty acids in both males and females. Based on physiological and biochemical variables, study subjects tolerated oral administration of 15 and 30g Arg/day without adverse events. We conclude that a long-term safe level of dietary Arg supplementation is at least 30g/day in adult humans.