Francis C. Lau

Safety and toxicological evaluation of a novel chromium(III) dinicocysteinate complex

Chromium(III) is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Chromium(III) dinicocysteinate (CDNC) is a unique form of bioavailable chromium(III). This study was focused on determining the broad spectrum safety of CDNC. Acute oral, acute dermal, primary dermal and eye irritation studies, Ames’ bacterial reverse mutation assay, mammalian erythrocyte micronucleus test, and a 90-day dose-dependent oral toxicity study were conducted. Acute oral and dermal LD50 of CDNC was found to be greater than 2000 mg/kg in Sprague-Dawley rats. A primary skin irritation study in New Zealand Albino rabbits demonstrated CDNC as slightly irritating. An eye irritation study exhibited that CDNC is moderately irritating. Ames’ bacterial reverse mutation assay and mammalian erythrocyte micronucleus test demonstrated CDNC as non-mutagenic. A dose-dependent 90-day oral toxicity study demonstrated no significant toxicity of CDNC. Body weight, food and water consumption, selected organ weights (expressed as percentages of body or brain weights), ocular health, hematology, blood chemistry, and histopathology showed no abnormal changes. Clinical and histopathological evaluation of CDNC identified a dose level of 5.7 mg/kg/day as the no observed adverse effect level (NOAEL). Overall, these results demonstrate the broad spectrum safety of CDNC.

Nutrigenomic analysis of diet-gene interactions on functional supplements for weight management.

Recent advances in molecular biology combined with the wealth of information generated by the Human Genome Project have fostered the emergence of nutrigenomics, a new discipline in the field of nutritional research. Nutrigenomics may provide the strategies for the development of safe and effective dietary interventions against the obesity epidemic. According to the World Health Organization, more than 60% of the global disease burden will be attributed to chronic disorders associated with obesity by 2020. Meanwhile in the US, the prevalence of obesity has doubled in adults and tripled in children during the past three decades. In this regard, a number of natural dietary supplements and micronutrients have been studied for their potential in weight management. Among these supplements, (–)-hydroxycitric acid (HCA), a natural extract isolated from the dried fruit rind of Garcinia cambogia, and the micronutrient niacin-bound chromium(III) (NBC) have been shown to be safe and efficacious for weight loss. Utilizing cDNA microarrays, we demonstrated for the first time that HCA-supplementation altered the expression of genes involved in lipolytic and adipogenic pathways in adipocytes from obese women and up-regulated the expression of serotonin receptor gene in the abdominal fat of rats. Similarly, we showed that NBC-supplementation up-regulated the expression of myogenic genes while suppressed the expression of genes that are highly expressed in brown adipose tissue in diabetic obese mice. The potential biological mechanisms underlying the observed beneficial effects of these supplements as elucidated by the state-of-the-art nutrigenomic technologies will be systematically discussed in this review.

Safety assessment of a calcium-potassium salt of (−)-hydroxycitric acid

The safety of Garcinia cambogiaextract, its active ingredient (–)-hydroxycitric acid (HCA), and the marketed weight management formula, Super CitriMax® (HCA-SX), is supported by numerous in vitro and animal experimental studies as well as several clinical studies. HCA-SX has been shown to reduce appetite, inhibit fat synthesis, and decrease body weight. A series of toxicological tests including acute, short-term, and sub-chronic studies as well as teratogenicity/reproduction and genotoxicity studies were performed on HCA-SX. In the acute oral toxicity study, administration of a single dose of 5,000 mg/kg of HCA-SX did not reveal any significant changes for all examined tissues. Following the high dose safety testing, there were no remarkable changes or differences observed in any of the experimental conditions monitored. There were no macroscopic abnormalities for any examined tissues at scheduled necropsies. On the basis of these findings, the consumption of HCA-SX at dose level of up to 4667 mg/day is considered safe.

Safety and toxicological evaluation of Meratrim®: an herbal formulation for weight management.

Meratrim is a unique dietary ingredient consisting of extracts from Sphaeranthus indicus flower heads and Garcinia mangostana fruit rind. Clinical studies have demonstrated that Meratrim is effective and well-tolerated in weight management. Herein we assessed the broad spectrum safety of Meratrim in a battery of in vitro and animal toxicological studies including a sub-chronic repeated-dose 13-week oral toxicity study to determine the no-observable-adverse-effect-level (NOAEL). The LD50 levels of Meratrim in Sprague-Dawley (SD) rats, as determined by the acute oral and dermal toxicity studies, were >5000 and >2000 mg/kg body weight, respectively. The primary skin and eye irritation tests classified Meratrim as non-irritating to the skin and mildly irritating to the eye. Genotoxicity studies showed that Meratrim is non-mutagenic. In the repeated-dose 13-week oral toxicity study, SD rats were orally gavaged with Meratrim at 0, 250, 500 or 1000 mg/kg/day. No morbidity, mortality, or significant adverse events were observed either during the course of the study or on the 13th week. The NOAEL of Meratrim was concluded to be 1000 mg/kg of body weight/day in male and female SD rats. These results, combined with the tolerability of Meratrim in the human clinical trials, demonstrate the broad spectrum safety of Meratrim.

Safety and toxicological evaluation of undenatured type II collagen

Previous research has shown that undenatured type II collagen is effective in the treatment of arthritis. The present study evaluated the broad-spectrum safety of UC-II by a variety of toxicological assays including acute oral, acute dermal, primary dermal irritation, and primary eye irritation toxicity. In addition, genotoxicity studies such as Ames bacterial reverse mutation assay and mouse lymphoma tests, as well as a dose-dependent 90-day sub-chronic toxicity study were conducted. Safety studies indicated that acute oral LD50 of UC-II was greater than 5000 mg/kg in female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of UC-II was determined to be greater than 2000 mg/kg. Primary skin irritation tests conducted on New Zealand Albino rabbits classified UC-II as slightly irritating. Primary eye irritation tests conducted on rabbits indicated that UC-II was moderately irritating to the eye. UC-II did not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Similarly, UC-II did not induce a mutagenic effect in the gene mutation test in mouse lymphoma cells either with or without metabolic activation. A dose-dependent 90-day sub-chronic toxicity study revealed no pathologically significant changes in selected organ weights individually or as percentages of body or brain weights. No significant changes were observed in hematology and clinical chemistry. Therefore, the results from the current study show a broad-spectrum safety profile of UC-II.

The Benefits of Antioxidant-Rich Fruits on Skin Health

Publisher Summary Skin is the largest organ that is under constant assault by environmental oxidative stress including ultraviolet radiation (UVR), air pollutants, and chemical oxidants. Premature skin aging may occur due to factors such as external oxidative stress as well as smoking, imbalanced nutrition, excessive dieting, and mental stress. Studies suggest that antioxidants regulate the biomarkers associated with premature aging by reducing oxidative stress including environmental stress such as ozone and cigarette smoking. Oral and topical natural antioxidant treatments protect against the development of premature skin aging due to oxidative damage. Therefore, natural fruits and vegetables rich in antioxidants may protect skin against premature aging. The focus of this chapter is on the beneficial effects of antioxidant-rich berries on skin health. Consuming natural antioxidants provides a plethora of health benefits, including lowering age-related oxidative stress and inflammation. Anthocyanins are the common components of fruits and vegetables, particularly in berries, which provide the bright red, blue, and purple hues to the plants. Anthocyanins are naturally occurring antioxidants. In vitro and in vivo studies have shown that berry anthocyanins possess potent antioxidant activity and many potential health benefits, including cardiovascular protection, anticarcinogenic potential, antidiabetic properties, brain function enhancement, ocular and vision health, urinary tract health, and skin health. Based on these health benefits, a formulation of a synergistic blend (OptiBerry) containing wild blueberry, bilberry, cranberry, elderberry, strawberry, and raspberry seed extracts was developed which has been found to be superior in bioavailability and antioxidative properties, providing whole-body antioxidant protection.

Ricin and Abrin

Publisher Summary Human toxicity of castor beans (ricin) and jequirity seeds (abrin) has been acknowledged throughout medical history, worldwide. Ricin and abrin are natural protein toxins isolated from plant seeds Ricinus communis and Abrus precatorius, respectively. Ricin and abrin share extensive identity and structural similarities of two polypeptide chains: an A-chain subunit and a larger B-chain subunit linked by a disulfide bond. The mechanisms of toxic action of abrin and ricin are also similar in which the B-chain achieves cellular recognition and binding function to facilitate toxin transport across the cell membrane whereas, the A-chain, once internalized by the cell, blocks protein synthesis by catalytically modifying the ribosomes. Both toxins ultimately kill target cells in animal or cell culture models by both necrosis and apoptosis. Numerous laboratory studies in mammals have demonstrated that ricin and abrin are highly toxic and potentially fatal to animals and humans. Major symptoms of both ricin and abrin poisoning are dependent on the route of exposure, the dose received, or the content of toxin in the seed. There is no specific treatment for ricin or abrin. Therefore, the only recommendation is to rid the body of the toxins as quickly as possible. Ricin and abrin poisoning is treated by giving victims the appropriate supportive medical care to minimize the effects of the poisoning. Cases of gastrointestinal exposure are the best managed by vigorous gastric decontamination with activated charcoal, followed by use of cathartics such as magnesium citrate.

Supplementation: Its Evolving Role in Prevention

Modern Western thinking expresses reliance on nutritional intervention as well as behavioral modalities such as meditation or acupuncture as “alternative medicine,” with our twentieth-century construct of pharmaceutical and surgical interventions cast as “mainstream medicine.” This nomenclature lacks historical perspective, as traditional, largely plant-based medicine can be found in cultures around the globe, such as the Ayurvedic, Traditional Chinese Medicine, or the European phytochemistry traditions such as are represented today by the German Commission E monographs. Indeed, the modern pharmaceutical industry has heavily relied on natural products for medicinal chemistry leads and sometimes for pharmaceutical actives themselves. All nutrition-based approaches can be considered alternative medicine in the US, as the curriculum of most medical schools is tragically deficient in nutrition education (Am J Clin Nutr 83:941S–4S, 2006).

Enhanced Urinary Excretion of Lipid Metabolites Following Exposure to Structurally Diverse Toxicants: A Unique Experimental Model for the Assessment of Oxidative Stress

Structurally diverse toxicants in the environment are responsible for the production of reactive oxygen species (ROS) in biological systems. The accumulation of ROS results in oxidative stress and causes damage to macromolecules such as DNA, proteins, lipids and carbohydrates. Consequently, exposure to environmental oxidants increases the occurrence of a number of diseases as well as reproductive and developmental defects. One of the hallmarks of oxidant-induced oxidative stress is the production of fat metabolites caused by lipid peroxidation. Lipid metabolites such as acetaldehyde, acetone, formaldehyde and malondialdehyde can be quantified in biological fluids including serum and urine using high-performance liquid chromatography, gas chromatography and/or mass spectrometry. In this regard, the simultaneous detection of lipid metabolites using these procedures may provide a powerful tool for the rapid, accurate, reproducible and noninvasive assessment of oxidative stress induced by environmental exposure to toxicants. This chapter reviews the application of these methodologies in the evaluation of temporal effects of toxicant exposure on lipid peroxidation in a variety of experimental systems.