Insight Report: Size, Industry, Share, Growth and Forecast 2019-2024

The present invention relates to a process of production of a compound, which is useful as an intermediate (building block) in organic synthesis, especially in the synthesis of vitamin A or β-carotene and derivatives thereof, e.g. canthaxanthin, astaxanthin or zeaxanthin.

Disclosed are methods of purifying (20R) and (20S) analogs of 2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D3 to obtain the (20R) and (20S) analogs in crystalline form. The method includes the steps of preparing a solvent of either diethyl ether or a mixture of 2-propanol and hexane, dissolving a product containing the (20R) and (20S) analog to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.

Methods and compositions for treating 25-hydroxyvitamin D insufficiency and deficiency in a patient are described herein. The method includes orally administering to the patient a delayed, sustained release formulation including a first ingredient selected from the group consisting of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, or it includes gradually administering to the patient a sterile intravenous formulation including a first ingredient selected from the group consisting of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3.

The present invention provides novel 16,23-diene 25-oxime ether analogs of 1,25-dihydroxy vitamin D3, compositions comprising these compounds and methods of using these compounds as inhibitors of CYP24. In particular, the novel compound of the invention are useful for treating diseases which benefit from a modulation of the levels of 1,25-dihydroxy vitamin D3, for example, cell-proliferative disorders.

Disclosed are methods of purifying the compound (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.

This invention discloses N-cyclopropyl-(20R)-2-methylene-19,26,27-trinor-25-aza-vitamin D analogs, and specifically N-cyclopropyl-(20R)-2-methylene-19,26,27-trinor-25-aza-1α-hydroxyvitamin D3 and pharmaceutical uses therefor. This compound exhibits relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of leukemia, colon cancer, breast cancer, skin cancer or prostate cancer.

This invention discloses 3-desoxy-2-methylene-19-nor-vitamin D analogs, and specifically (20S)-3-desoxy-2-methylene-1α,25-dihydroxy-19-nor-vitamin D3 and (20R)-3-desoxy-2-methylene-1α,25-dihydroxy-19-nor-vitamin D3 as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to monocytes thus evidencing use as anti-cancer agents especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also exhibit relatively high calcemic activity evidencing use in the treatment of bone diseases.

To provide a novel vitamin D3 derivative useful as a therapeutic agent for osteoporosis. Provided is a vitamin D3 derivative represented by the following formula (1) or a medicinally acceptable solvate thereof: wherein R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkylcarbonyloxyalkyl group with each alkyl having 1 to 6 carbon atoms, or an arylcarbonyloxyalkyl group with the aryl having 6 to 10 carbon atoms and the alkyl having 1 to 6 carbon atoms; R2 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or, together with the other R2 and the carbon atom to which they are bound to, may form a cyclic alkyl group having 3 to 6 carbon atoms; R3 represents an alkyl group having 1 to 6 carbon atoms or, together with the other R3 and the carbon atom to which they are bound to, may form a cyclic alkyl group having 3 to 6 carbon atoms; X represents an oxygen atom or a methylene group; and n represents an integer of 1 or 2.

The present invention provides a compound which functions as a selective vitamin D receptor modulator and has action-selectivity or tissue-selectivity such that it does not induce hypercalcemia but causes other effects. There is provided a compound represented by formula (I), a solvate thereof or a prodrug thereof. wherein m and n each independently represent 1 or 0;R represents a hydrogen atom or an alkyl group;Y represents an ethane-1,1-diyl group or an ethyne-1,2-diyl group; andZ1 represents a hydrogen atom and Z2 represents a hydroxyalkoxy group, orZ1 and Z2 jointly form a methylene group.

Disclosed are methods of purifying the compound (20R)-19-nor-24-difluoro-1α,25-dihydroxyvitamin D3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.

The invention relates to compounds and methods for targeting radionuclide-based imaging agents to cells having receptors for a vitamin, or vitamin receptor binding derivative or analog thereof, by using such a vitamin as the targeting ligand for the imaging agent. The vitamin-based compounds can be used to target radionuclides to cells, such as a variety of tumor cell types, for use in diagnostic imaging of the targeted cells.

Provided are a detection agent for detecting hydroxy vitamin D, preparation method thereof, and use thereof in 25-hydroxy vitamin D immunological detection. The detection agent comprises a conjugate formed by a 25-hydroxy vitamin D antigen derivative and protein carrier, and magnetic spheres coated by the conjugate. Also provided is a 25-hydroxy vitamin D detection kit comprising the detection agent.

More importantly right now, does a higher level of vitamin D enable you to fight off infections such as influenza and COVID? Of course, as I stated at the beginning, in the middle of the COVID maelstrom, people are claiming everything about everything.

How long have you been trying to build a team and generate a residual income with Usana Vitamins? Well whether it is 3 days. 3 months or 3 years it really does not matter. You will benefit from the information I am going to share with you today.

Some people might want to consider it during the pandemic. Here's why.

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R^–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by ²H/¹³C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.

Belinda S. O’Connell
Aug 1, 2001; 14:
Articles

Shani V. Davis
Aug 1, 2011; 24:148-153
Feature Article/Vitamin D in African Americans

Teresa Martin
May 1, 2011; 24:113-118
Pharmacy and Therapeutics

(Anglia Ruskin University) A new study has found an association between low average levels of vitamin D and high numbers of COVID-19 cases and mortality rates across 20 European countries.

Belinda S. O’Connell
Aug 1, 2001; 14:
Articles

Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Some molecules of retinaldehyde upon release from opsin are efficiently reduced to retinol. Other molecules are released into the lipid phase of the disc membrane where they form a conjugate (N-retinylidene-PE, NRPE) through a Schiff base linkage with phosphatidylethanolamine (PE). The reversible formation of NRPE serves as a transient sink for retinaldehyde that is intended to return retinaldehyde to the visual cycle. However, if instead of hydrolyzing to PE and retinaldehyde, NRPE reacts with a second molecule of retinaldehyde a synthetic pathway is initiated that leads to the formation of multiple species of unwanted bisretinoid fluorophores. We report on recently identified members of the bisretinoid family some of which differ with respect to the acyl chains associated with the glycerol backbone. We discuss processing of the lipid moieties of these fluorophores in lysosomes of retinal pigment epithelial (RPE) cells, their fluorescence characters and new findings related to light and iron-associated oxidation of bisretinoids.

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R^–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by ²H/¹³C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.

Meritxell Morró
May 1, 2020; 69:927-939
Islet Studies

Despite high quality systematic reviews reporting ineffectiveness, many guideline groups continue to recommend vitamin D supplementation (with or without calcium) for fall or fracture prevention. Recently Public Health England recommended that everyone needs vitamin D equivalent to an average daily intake of 10 μg (400 IU) to protect bone and...

Welcome to this, trial run, of a new kind of BMJ podcast - here we’re going to be focusing on all things EBM. Duncan Jarvies, Helen Macdonald and Carl Heneghan - and occasional guests- will be back every month to discuss what's been happening in the world of evidence. We'll bring you our Verdict on what you should start or stop doing, geek out...

Antonio Ceriello
Jan 1, 1991; 14:68-72
Short Report

Massimo Cigolini
Mar 1, 2006; 29:722-724
BR Cardiovascular and Metabolic Risk

Earl S. Ford
May 1, 2005; 28:1228-1230
BR Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes

Vitamin D levels in the general population have decreased considerably over the past decade. The implications of maternal vitamin D insufficiency during pregnancy for offspring neurocognitive development remain unclear.

Studying a large sample and using a prospective longitudinal design, this study demonstrates a link between maternal vitamin D insufficiency during pregnancy and offspring language impairment. There was no association with childhood behavioral or emotional problems. (Read the full article)

Postpartum vitamin A supplementation is a strategy to combat vitamin A deficiency and seems to reduce maternal/infant morbidity and mortality. However, controversies exist regarding which dose has a greater efficacy, 200 000 IU (WHO protocol) or 400 000 IU (IVACG protocol).

In this study, postpartum maternal supplementation with 400 000 IU of vitamin A did not provide any additional beneficial effect in reducing infant morbidity compared with the standard dose of 200 000 IU. (Read the full article)

There is no literature on the concentrations of vitamin B₆ vitamers in cerebrospinal fluid of preterm and term newborn infants. This knowledge, however, is highly important, because vitamin B₆ plays a pivotal role in brain development and functioning.

In cerebrospinal fluid of newborn infants, B₆ vitamer concentrations are strongly dependent on postmenstrual age, indicating that vitamin B₆ homeostasis in brain differs between preterm and term newborns. This has implications for the evaluation of epilepsy and vitamin B₆ deficiency. (Read the full article)

Vitamin D is essential for bone health and for cardiovascular and immune function. In critically ill adults, vitamin D deficiency is common and associated with sepsis and with higher critical illness severity. The influence on pediatric critical illness is unclear.

We found a high prevalence of vitamin D deficiency in critically ill children, which was associated with higher critical illness severity. Vitamin D deficiency was less common in younger patients, in non-Hispanic white patients, in patients admitted over the summer, and in children taking supplemental vitamin D, with increasing amounts being more protective. (Read the full article)

Vitamin D is a pleiotropic hormone important for proper functioning of multiple organs. Adult critical care studies have suggested vitamin D as a modifiable risk factor. No studies have investigated the prevalence, risk factors, or role in pediatric critical illness.

This study provides evidence that the majority of critically ill children have vitamin D deficiency at the time of PICU admission, and that lower levels are associated with hypocalcemia, catecholamine administration, significant fluid bolus requirements, and longer PICU admissions. (Read the full article)

Cholestasis predisposes to the development of fat-soluble vitamin (FSV) deficiency. D-α tocopheryl polyethylene glycol-1000 succinate and coadministered FSVs are absorbed in spite of cholestasis.

Infants with biliary atresia with total bilirubin >2 mg/dL are at risk for fat-soluble vitamin (FSV) deficiency. A multivitamin preparation containing d-α tocopheryl polyethylene glycol-1000 succinate alone is not effective in treating biochemical FSV insufficiency in cholestatic infants. (Read the full article)

A growing number of epidemiologic studies suggest that individuals with lower vitamin D levels are at higher risk of acute respiratory tract infection. Randomized controlled trials are needed to determine if vitamin D supplementation would decrease this risk.

In a randomized controlled trial of 247 Mongolian children with vitamin D deficiency in winter, with double-blinding and 99% follow-up, vitamin D supplementation significantly reduced the risk of acute respiratory tract infections. (Read the full article)

Forearm fractures are unique injuries which are associated with lower bone mineral density in adults and white children. The relationships among bone mineral density, 25-hydroxyvitamin D status, and risk for forearm fracture have not been investigated in African American children.

Our data support an association between both lower bone mineral density and vitamin D deficiency and increased odds of forearm fracture in African American children. Promotion of bone health is indicated in this population. (Read the full article)

Despite numerous preventive strategies including prophylaxis with 400 IU/day of vitamin D in recent years, the deficiency of vitamin D in infants is still a global health problem.

This study reveals that the risk of vitamin D deficiency is high in exclusively breastfed infants, especially in winter, despite vitamin D supplementation. Therefore, it is suggested that an adjustment of vitamin D dosage for seasonal variation might be necessary. (Read the full article)

The rising burden of allergy is most evident in infancy, indicating the importance of early exposures. Reduced vitamin D status in pregnancy has been associated with atopy and respiratory outcomes, but there is less information on other early allergic outcomes.

Cord blood 25-hydroxyvitamin D₃ concentrations <50 nmol/L were highly prevalent in an Australian population. Lower vitamin D levels were associated with increased risk of eczema at 12 months of age, whereas there was no association with sensitization or food allergy. (Read the full article)

Cow’s milk consumption has opposite effects on vitamin D and iron levels in children; however, the amount of cow’s milk intake required for sufficient stores of vitamin D and iron is poorly understood, and existing guidelines on consumption are unclear.

Two cups of cow’s milk per day is sufficient to maintain healthy vitamin D and iron stores for most children. Wintertime vitamin D supplementation appears particularly important among children with darker skin pigmentation. (Read the full article)

Adequate vitamin D is essential for skeletal health in developing children. Although excess body weight is associated with risk of vitamin D deficiency, the national prevalence of vitamin D deficiency in overweight and obese children is unknown.

Vitamin D deficiency is highly prevalent in overweight and obese children, and severely obese and minority children are disproportionately affected. There are many modifiable factors associated with vitamin D deficiency in overweight and obese children. (Read the full article)

Hypovitaminosis D is common among children. Although there is prolific biochemical literature linking vitamin D to enteric immunologic function, there is a paucity of prospective data exploring the role of supplementation in prevention of diarrheal illnesses.

In a high-risk population, quarterly supplementation with 100 000 IU of vitamin D₃ did not reduce the risk for first or recurrent diarrheal illnesses in a population of children aged 1 to 29 months in a low-income inner city setting. (Read the full article)

Preterm infants are born with low serum levels and low body stores of tocopherol. Serum levels ≥0.5 mg/dL are required for protection against lipid peroxidation. Previous studies have shown good intestinal absorption of vitamin E given intragastrically to preterm infants.

Serum α-tocopherol increases after a single 50-IU/kg dose of vitamin E as dl-α-tocopheryl acetate given intragastrically to very preterm infants soon after birth; however, 30% of infants still have serum α-tocopherol level <0.5 mg/dL 24 hours after dosing. (Read the full article)

A serum 25-hydroxyvitamin D (25(OH)D) concentration of 20 ng/mL meets the requirements of at least 97.5% of the population older than 1 year. A recommended dietary intake to achieve this serum 25(OH)D concentration has not been established during infancy.

Daily maternal (during pregnancy) and then infant vitamin supplementation with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥20 ng/mL during infancy with the higher dose sustaining this increase for longer. (Read the full article)

Studies have shown dysfunction in the baroreflex mechanism and the autonomic nervous system, particularly in the sympathetic nervous system, in the pathophysiology of chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and syncope.

Vitamin B₁₂ deficiency is associated with postural orthostatic tachycardia syndrome in adolescence. (Read the full article)

Despite widespread prevalence of vitamin D deficiency, there is a paucity of evidence on the appropriate supplemental dose in preterm infants. Various professional organizations empirically recommend different doses of vitamin D, ranging from 400 to 1000 IU per day.

Daily vitamin D supplementation at a dose of 800 IU compared with 400 IU significantly reduces the prevalence of vitamin D deficiency in preterm infants. The clinical significance of achieving vitamin D sufficiency needs to be studied in larger trials. (Read the full article)

Many young children are at risk for caries, which is the most common chronic disease of childhood. As primary teeth begin to develop in utero, prenatal influences are believed to affect the integrity of enamel and subsequent resistance to decay.

This study shows, for the first time, that maternal prenatal 25-hydroxyvitamin D levels may have an influence on the primary dentition and the development of early childhood caries. Specifically, lower levels are associated with increased risk of caries in infants. (Read the full article)

The World Health Organization recommends using vaccination contacts to deliver high-dose vitamin A supplementation (VAS) to children aged 6 to 59 months. The effect of this policy on overall child mortality has not been assessed.

In this first randomized controlled trial of VAS at routine vaccination contacts after 6 months, VAS had no overall effect on mortality but was associated with reduced mortality in girls and increased mortality in boys. (Read the full article)