cholecalciferol and gamma-sitosterol

Prostatism and erectile dysfunction (ED) are highly prevalent and closely comorbid. Prescription treatments are limitingly expensive but robust in mechanisms of action (MoA). Nutritional supplements (NS) are low-cost but inadequately supported by evidence. Do any NS use robust MoA? Could their efficacy be amplified via dosing, concentration of active principles, and/or use in combination? The goal is to develop an effective NS for prostatism and ED using the MoA of prescription treatments. Literature reviews were conducted on dietary supplements for prostatism or ED and MoA of relevant drugs. The most promising NS employing these MoA were chosen. A pilot study of a prototype combination was conducted. A protocol was created for an adequate dose-response trial to test the NS combination in men with ED and prostatism. The main measures were response rates, International Prostate Symptom Score, and International Index of Erectile Function. For drugs, the MoAs best proven for prostatism and ED were nitric oxide augmentation, mild androgen inhibition, and anti-inflammatory effects. The following NS best simulate these MoA and are best supported for efficacy; for prostatism: beta sitosterol; for ED: panax ginseng, arginine, and citrulline. Pilot clinical data provided support. A plan for a formal dose-response clinical trial was approved by a central institutional review board. NS using effective MoA might suffice for prostatism and ED. Pilot testing of a combination NS with the best-supported MoA supported further development. A dose-response trial should be conducted using adequate doses of L-citrulline, beta-sitosterol, ginseng, and vitamin D3.

Topics: Arginine; Cholecalciferol; Citrulline; Clinical Trials as Topic; Dietary Supplements; Erectile Dysfunction; Humans; Male; Meta-Analysis as Topic; Middle Aged; Panax; Pilot Projects; Plant Extracts; Prostatism; Sitosterols; Urination

Adequate vitamin D status is necessary and beneficial for health, although deficiency and insufficiency are very common. As cholecalciferol (vitamin D(3) ) structure is close to cholesterol structure, we hypothesized that phytosterols, frequently used to decrease cholesterol, intestinal absorption and consequently to reduce hypercholesterolemia, may also interact with cholecalciferol absorption.. β-Sitosterol effect on cholecalciferol postprandial response was first assessed in mice. We then evaluated the effect of different sterols on (i) cholecalciferol micellar incorporation, (ii) cholecalciferol apical uptake and (iii) basolateral efflux in vitro or ex vivo. In mice, cholecalciferol bioavailability was 15-fold lower in the presence of β-sitosterol (p<0.05). This can partly be explained by the fact that phytosterols significantly impaired cholecalciferol incorporation into mixed micelles (from -16 to -36% depending on sterol micellar composition). This can also be due to the fact that in Caco-2 cells and mouse intestinal explants, phytosterols significantly lowered cholecalciferol apical uptake (from -13 to -39%). Conversely, phytosterols had no effect on cholecalciferol secretion at the basolateral side of Caco-2 cells.. The present data suggest for the first time that phytosterols can interact with vitamin D(3) intestinal absorption. This interaction can be explained by a competition for micellar incorporation and for apical uptake.

Topics: Animals; Caco-2 Cells; Cholecalciferol; Cholesterol; Enterocytes; Humans; In Vitro Techniques; Intestinal Absorption; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Micelles; Phytosterols; Postprandial Period; Sitosterols; Vitamin D

Among the many functions of vitamin D (VD) is its role in the immunomodulation of macrophage. As VD deficiency is a wide-spread nutritional problem, there is a tendency for the public to overdose with vitamin D supplementation which can result in hypercalcemia and several associated disorders. The present study was designed to investigate the possibility that combining low doses of vitamin D with β-sitosterol (SIT), a common phytosterol in the diet without toxicity, enhances the efficacy of the vitamin. Murine macrophages were stimulated with LPS and supplemented with VD3 (80 nM) and SIT (8 μM) for 24 hr and examined for cell proliferation, release of nitric oxide (NO) and cytokines and the activation of NFκB. SIT (8 μM) was found to reduce cell proliferation by 62% while VD3 was found to be not effective. In combination, SIT and VD3 reduced cell proliferation by 75%.The amount of NO released, as influenced by 8 μM SIT or 80 nM VD3 treatments, was not significantly different from control. Combining SIT and VD3, resulted in a 220% greater increase in NO release compared to control. The SIT + VD3 treatment brought about significant increase in all the cytokine release, regardless of whether they were pro- or anti-inflammatory. The effects were either additive or synergistic. We conclude that SIT enhances the action of VD3 on the immune function of macrophages which could be beneficial to vitamin D deficient individuals and to those with autoimmune diseases such as multiple sclerosis.

Topics: Animals; Cell Line; Cell Proliferation; Cholecalciferol; Cytokines; Drug Synergism; Immunologic Factors; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; NF-kappa B; Nitric Oxide; Sitosterols; Vitamins

The rate of non-specific lipid transfer protein (nsLTP)-mediated exchange is independent of structure for dissimilar sterols: cholesterol, lanosterol, sitosterol and vitamin D-3. Conversely, the nsLTP-mediated exchange of cholesterol is markedly affected by the phospholipid composition of the donor liposome. Negatively charged phosphatidylglycerols strikingly increase cholesterol exchange in the presence of nsLTP while not altering the exchange in the absence of nsLTP. The presence of unsaturated acyl chains in the phospholipid enhances exchange. Sphingomyelin drastically decreases cholesterol exchange, as does di-O-alkylphosphatidylcholine. Decreased exchange produced by these substitutions can be reversed by addition of phosphatidylcholine. The presence of an acyl group and a negative charge in the phospholipid are critical for the nsLTP-mediated transfer of cholesterol. In addition to these studies on composition of the donor membrane, the charge on the membrane also appears critical. Maximal exchange rates accompany optimization of potential interaction of negatively charged surface and the basic nsLTP. The nsLTP also mediates an approximately equal rate of exchange of cholesterol and phosphatidylcholine. However, approaching equilibrium, only half of the phospholipid can be exchanged while there is exchange of about 90% of cholesterol. Thus, it appears that only the phospholipid in an outer membrane layer may be available whereas cholesterol is fully available. Therefore, in contrast to a 'carrier' model we suggest that nsLTP facilitates exchange by binding to the membranes, and binding is highly dependent upon lipid composition. Once bound, the protein functions as a bridge between membranes, thus, facilitating exchange.

Topics: Biological Transport; Carrier Proteins; Cholecalciferol; Cholesterol; Lanosterol; Lipids; Liposomes; Phosphatidylcholines; Phosphatidylglycerols; Phospholipids; Plant Proteins; Sitosterols; Sphingomyelins; Sterols