Elisabeth Stoecklin

The role of menaquinones (vitamin K 2 ) in human health

Recent reports have attributed the potential health benefits of vitamin K beyond its function to activate hepatic coagulation factors. Moreover, several studies have suggested that menaquinones, also known as vitamin K2, may be more effective in activating extra-hepatic vitamin K-dependent proteins than phylloquinone, also known as vitamin K1. Nevertheless, present dietary reference values (DRV) for vitamin K are exclusively based on phylloquinone, and its function in coagulation. The present review describes the current knowledge on menaquinones based on the following criteria for setting DRV: optimal dietary intake; nutrient amount required to prevent deficiency, maintain optimal body stores and/or prevent chronic disease; factors influencing requirements such as absorption, metabolism, age and sex. Dietary intake of menaquinones accounts for up to 25% of total vitamin K intake and contributes to the biological functions of vitamin K. However, menaquinones are different from phylloquinone with respect to their chemical structure and pharmacokinetics, which affects bioavailability, metabolism and perhaps impact on health outcomes. There are significant gaps in the current knowledge on menaquinones based on the criteria for setting DRV. Therefore, we conclude that further investigations are needed to establish how differences among the vitamin K forms may influence tissue specificities and their role in human health. However, there is merit for considering both menaquinones and phylloquinone when developing future recommendations for vitamin K intake.

Pharmacokinetics of oral vitamin D3 and calcifediol

AIM Long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol (the 25-hydroxyvitamin D3 metabolite) are not well studied. Additionally, it is unclear whether bolus doses of vitamin D3 or calcifediol lead to 25(OH)D3 plasma concentrations considered desirable for fracture prevention (30ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D3 during different vitamin D3 and calcifediol supplementation regimens. METHODS In this seven-arm, randomised, double-blind, controlled parallel-group study, 35 healthy females aged 50 - 70years (5 per group) received 20μg calcifediol or vitaminD3 daily, 140μg calcifediol or vitaminD3 weekly, for 15weeks, or a single bolus of either 140μg calcifediol, or vitaminD3, or both. 25(OH)D3 plasma concentrations were quantified using LC-MS/MS in 14 clinical visits among all participants. RESULTS For daily (weekly) dosing, the area under the concentration-time curve (AUC0-24h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitaminD3. After 15weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D3 concentrations >30ng/mL (mean, 16.8days), but only 70% in the vitaminD3 daily or weekly groups reached this concentration (mean, 68.4days). A single dose of 140μg calcifediol led to 117% higher 25(OH)D3 AUC0-96h values than 140μg vitaminD3, while the simultaneous intake of both did not further increase exposure. CONCLUSIONS Calcifediol given daily, weekly, or as a single bolus is about 2-3 times more potent in increasing plasma 25(OH)D3 concentrations than vitamin D3. Plasma 25(OH)D3 concentrations of 30ng/mL were reached more rapidly and reliably with calcifediol.

Dietary vitamin E modulates differential gene expression in the rat hippocampus: potential implications for its neuroprotective properties

Abstract A wide range of cell culture, animal and human epidemiological studies are suggestive of a role of vitamin E (VE) in brain function and in the prevention of neurodegeneration. However, the underlying molecular mechanisms remain largely unknown. In the current investigation Affymetrix gene chip technology was utilised to establish the impact of chronic VE deficiency on hippocampal genes expression. Male albino rats were fed either a VE deficient or standard diet (60?mg/kg feed) for a period of 9 months. Rats were sacrificed, the hippocampus removed and genes expression established in individual animals. VE deficiency showed to have a strong impact on genes expression in the hippocampus. An important number of genes found to be regulated by VE was associated with hormones and hormone metabolism, nerve growth factor, apoptosis, dopaminergic neurotransmission, and clearance of amyloid-beta and advanced glycated endproducts. In particular, VE strongly affected the expression of an array of genes encoding for proteins directly or indirectly involved in the clearance of amyloid beta, changes which are consistent with a protective effect of VE on Alzheimers disease progression.

Cortical Gene Expression in the Vitamin E-Deficient Rat: Possible Mechanisms for the Electrophysiological Abnormalities of Visual and Neural Function

In mammals, severe and chronic deficiency of vitamin E (α-tocopherol) is associated with a characteristic neurological syndrome. Previously, we have shown that this syndrome is accompanied by electrophysiological abnormalities of neural and visual function. To investigate the molecular basis of the observed abnormalities, we used microarrays to monitor the expression of ∼14,000 genes in the cerebral cortex from rats which had received diets containing 0, 1.25 and 5.0 mg/kg diet of all-rac-α-tocopheryl acetate for 14 months. Compared to the groups receiving 1.25 and 5.0 mg/kg α-tocopheryl acetate, a total of 11 genes were statistically significantly upregulated (≧1.3-fold) and 34 downregulated (≤1.3-fold) in the vitamin E-deficient group. Increased expression was observed for the genes encoding the antioxidant enzyme catalase and the axon guidance molecule tenascin-R, while decreased expression was detected for genes encoding protein components of myelin and determinants of neuronal signal propagation. Thus our observations suggest that vitamin E deficiency results in transcriptional alterations in the cerebral cortex of the rat which are consistent with the observed neurological and electrophysiological alterations.