The objective of this review was to apply the risk assessment methodology used by the Food and Nutrition Board (FNB) to derive a revised safe Tolerable Upper Intake Level (UL) for vitamin D. New data continue to emerge regarding the health benefits of vitamin D beyond its role in bone. The intakes associated with those benefits suggest a need for levels of supplementation, food fortification, or both that are higher than current levels. A prevailing concern exists, however, regarding the potential for toxicity related to excessive vitamin D intakes. The UL established by the FNB for vitamin D (50 microg, or 2000 IU) is not based on current evidence and is viewed by many as being too restrictive, thus curtailing research, commercial development, and optimization of nutritional policy. Human clinical trial data published subsequent to the establishment of the FNB vitamin D UL published in 1997 support a significantly higher UL. We present a risk assessment based on relevant, well-designed human clinical trials of vitamin D. Collectively, the absence of toxicity in trials conducted in healthy adults that used vitamin D dose > or = 250 microg/d (10,000 IU vitamin D3) supports the confident selection of this value as the UL.

We document the configuration and emergent simulation features from the Geophysical Fluid Dynamics Laboratory (GFDL) OM4.0 ocean/sea ice model. OM4 serves as the ocean/sea ice component for the GFDL climate and Earth system models. It is also used for climate science research and is contributing to the Coupled Model Intercomparison Project version 6 Ocean Model Intercomparison Project. The ocean component of OM4 uses version 6 of the Modular Ocean Model and the sea ice component uses version 2 of the Sea Ice Simulator, which have identical horizontal grid layouts (Arakawa C‐grid). We follow the Coordinated Ocean‐sea ice Reference Experiments protocol to assess simulation quality across a broad suite of climate‐relevant features. We present results from two versions differing by horizontal grid spacing and physical parameterizations: OM4p5 has nominal 0.5° spacing and includes mesoscale eddy parameterizations and OM4p25 has nominal 0.25° spacing with no mesoscale eddy parameterization. Modular Ocean Model version 6 makes use of a vertical Lagrangian‐remap algorithm that enables general vertical coordinates. We show that use of a hybrid depth‐isopycnal coordinate reduces the middepth ocean warming drift commonly found in pure z* vertical coordinate ocean models. To test the need for the mesoscale eddy parameterization used in OM4p5, we examine the results from a simulation that removes the eddy parameterization. The water mass structure and model drift are physically degraded relative to OM4p5, thus supporting the key role for a mesoscale closure at this resolution.

Abstract. The Canadian Earth System Model version 5 (CanESM5) is a global model developed to simulate historical climate change and variability, to make centennial-scale projections of future climate, and to produce initialized seasonal and decadal predictions. This paper describes the model components and their coupling, as well as various aspects of model development, including tuning, optimization, and a reproducibility strategy. We also document the stability of the model using a long control simulation, quantify the model's ability to reproduce large-scale features of the historical climate, and evaluate the response of the model to external forcing. CanESM5 is comprised of three-dimensional atmosphere (T63 spectral resolution equivalent roughly to 2.8∘) and ocean (nominally 1∘) general circulation models, a sea-ice model, a land surface scheme, and explicit land and ocean carbon cycle models. The model features relatively coarse resolution and high throughput, which facilitates the production of large ensembles. CanESM5 has a notably higher equilibrium climate sensitivity (5.6 K) than its predecessor, CanESM2 (3.7 K), which we briefly discuss, along with simulated changes over the historical period. CanESM5 simulations contribute to the Coupled Model Intercomparison Project phase 6 (CMIP6) and will be employed for climate science and service applications in Canada.

Introduction-To assess the benefit of higher dose and higher achieved 25-hydroxyvitamin D levels (25(OH)D) versus any associated risk.

No abstract

Creatine has become one of the most popular dietary supplements in the sports nutrition market. The form of creatine that has been most extensively studied and commonly used in dietary supplements is creatine monohydrate (CM). Studies have consistently indicated that CM supplementation increases muscle creatine and phosphocreatine concentrations by approximately 15-40%, enhances anaerobic exercise capacity, and increases training volume leading to greater gains in strength, power, and muscle mass. A number of potential therapeutic benefits have also been suggested in various clinical populations. Studies have indicated that CM is not degraded during normal digestion and that nearly 99% of orally ingested CM is either taken up by muscle or excreted in urine. Further, no medically significant side effects have been reported in literature. Nevertheless, supplement manufacturers have continually introduced newer forms of creatine into the marketplace. These newer forms have been purported to have better physical and chemical properties, bioavailability, efficacy, and/or safety profiles than CM. However, there is little to no evidence that any of the newer forms of creatine are more effective and/or safer than CM whether ingested alone and/or in combination with other nutrients. In addition, whereas the safety, efficacy, and regulatory status of CM is clearly defined in almost all global markets; the safety, efficacy, and regulatory status of other forms of creatine present in today's marketplace as a dietary or food supplement is less clear.

A systematic review of published toxicology and human intervention studies was performed to characterize potential hazards associated with consumption of green tea and its preparations. A review of toxicological evidence from laboratory studies revealed the liver as the target organ and hepatotoxicity as the critical effect, which was strongly associated with certain dosing conditions (e.g. bolus dose via gavage, fasting), and positively correlated with total catechin and epigallocatechingallate (EGCG) content. A review of adverse event (AE) data from 159 human intervention studies yielded findings consistent with toxicological evidence in that a limited range of concentrated, catechin-rich green tea preparations resulted in hepatic AEs in a dose-dependent manner when ingested in large bolus doses, but not when consumed as brewed tea or extracts in beverages or as part of food. Toxico- and pharmacokinetic evidence further suggests internal dose of catechins is a key determinant in the occurrence and severity of hepatotoxicity. A safe intake level of 338 mg EGCG/day for adults was derived from toxicological and human safety data for tea preparations ingested as a solid bolus dose. An Observed Safe Level (OSL) of 704 mg EGCG/day might be considered for tea preparations in beverage form based on human AE data.

Abstract. The Canadian Earth System Model version 5 (CanESM5) is a global model developed to simulate historical climate change and variability, to make centennial scale projections of future climate, and to produce initialized seasonal and decadal predictions. This paper describes the model components and their coupling, as well as various aspects of model development, including tuning, optimization and a reproducibility strategy. We also document the stability of the model using a long control simulation, quantify the model's ability to reproduce large scale features of the historical climate, and evaluate the response of the model to external forcing. CanESM5 is comprised of three dimensional atmosphere (T63 spectral resolution/2.8°) and ocean (nominally 1°) general circulation models, a sea ice model, a land surface scheme, and explicit land and ocean carbon cycle models. The model features relatively coarse resolution and high throughput, which facilitates the production of large ensembles. CanESM5 has a notably higher equilibrium climate sensitivity (5.7 K) than its predecessor CanESM2 (3.8 K), which we briefly discuss, along with simulated changes over the historical period. CanESM5 simulations are contributing to the Coupled Model Intercomparison Project Phase 6 (CMIP6), and will be employed for climate science and service applications in Canada.