-
1.
Safety and tolerability of a natural supplement containing glucosinolates, phytosterols and citrus flavonoids in adult women: a randomized phase I, placebo-controlled, multi-arm, double-blinded clinical trial.
Villar-López, M, Soto-Becerra, P, Curse Choque, R, Al-Kassab-Córdova, A, Bernuy-Barrera, F, Palomino, H, Rojas, PA, Vera, C, Lugo-Martínez, G, Mezones-Holguín, E
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(10):906-913
Abstract
OBJECTIVE To evaluate the safety and tolerability of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids (Warmi®, Lima Perú;) in otherwise healthy adult women. METHODS This was a phase-I, randomized parallel three arms, double-blinded, and a placebo-controlled clinical trial. A total of 55 participants aged 18-40 were randomly assigned to one of three groups to receive for three months: (1) an oral herbal supplement of 1650 mg/day; (2) an oral herbal supplement of 3300 mg/day; or (3) an oral placebo 3300 mg/day. The primary endpoints were oral safety and tolerability of the supplement. The secondary endpoint was its effect on vital functions, anthropometrics, and laboratory tests. We used an exploratory approach by covariance analysis (ANCOVA) adjusted for the variables' baseline value for the secondary outcomes. RESULTS All women completed three months of follow-up, reporting no side effects. Our exploratory analysis revealed that treatment with the herbal supplement of 1650 mg/day was associated with increased glucose and uric acid levels. In comparison, the herbal supplement 3300 mg/day was associated with reduced breathing rate, increased basal temperature, and systolic blood pressure, both compared to the placebo group. However, despite significant differences, none of these was clinically significant. CONCLUSION The oral herbal supplement had a favorable safety and tolerability profile in studied women. There is a need to study its potential as an option to treat menopausal symptoms.
-
2.
Phytosterols Supplementation Reduces Endothelin-1 Plasma Concentration in Moderately Hypercholesterolemic Individuals Independently of Their Cholesterol-Lowering Properties.
Oliveira Godoy Ilha, A, Sutti Nunes, V, Silva Afonso, M, Regina Nakandakare, E, da Silva Ferreira, G, de Paula Assis Bombo, R, Rodrigues Giorgi, R, Marcondes Machado, R, Carlos Rocha Quintão, E, Lottenberg, AM
Nutrients. 2020;(5)
Abstract
Experimental and clinical studies have demonstrated the effect of phytosterols (PS) on reducing plasma levels of cholesterol and LDL-c, but the effects of plant sterols beyond cholesterol-lowering are still questionable. Since inflammation and endothelial dysfunction are involved in the pathogenesis of atherosclerosis, this study aims to evaluate the effect of PS on biomarkers involved in atherosclerosis progression and whether these effects are independent of alterations in plasma LDL-c levels. Thirty-eight moderately hypercholesterolemic volunteers (58 ± 12 years; LDL-c ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and lipid profiles and biomarkers for inflammation and endothelial dysfunction determined. The results showed that PS treatment reduced endothelin-1 plasma concentration by 11% (p = 0.02) independently of variations in plasma levels of LDL-c. No alterations were observed regarding fibrinogen, IL-6, hs-CRP, SAA, TNFα, or VCAM-1 between placebo and PS-treated groups. Furthermore, PS reduced total plasma cholesterol concentration (-5,5%, p < 0.001), LDL-c (-6.4%, p < 0.05), triglycerides (-8.3%, p < 0.05), and apo B (-5.3%, p < 0.05), without changing HDL-c concentration (p > 0.05). Therefore, PS supplementation effectively lowers endothelin-1 independently of the reductions in plasma levels of LDL-c, contributing to the comprehension of the effect of plant sterols on endothelial function and prevention of cardiovascular diseases.
-
3.
Noncholesterol Sterols as Surrogate Markers in Patients with Severe Alcoholic Hepatitis.
Sahlman, P, Nissinen, M, Simonen, P, Färkkilä, M
Lipids. 2018;(3):323-334
Abstract
Severe alcoholic hepatitis (AH) is a life-threatening condition lacking good serologic markers to tailor treatment and predict recovery. We examined the cholesterol metabolism in severe AH to explore prognostic markers and evaluate the profile of cholesterol precursors, cholestanol and phytosterols, in this context. We assessed serum cholesterol, cholesterol precursors, cholestanol, phytosterols, and biochemical markers in 24 patients with severe AH treated with prednisolone and randomized to ciprofloxacin in the ratio 1:1. Response to prednisolone was assessed with the Lille model. Evaluations were made between responders and nonresponders to corticosteroid treatment and during follow-up for 180 days. The findings were compared with those from patients with primary sclerosing cholangitis (PSC) (n = 156) and healthy individuals (n = 124). Responders to prednisolone had ~56-60% higher (p-value 0.032-0.044) serum ratios to cholesterol of phytosterols, while the lathosterol/campesterol ratio was ~76% (p = 0.031) lower compared to nonresponders. Stigmasterol/cholesterol predicted response to corticosteroid therapy. Surrogate markers of cholesterol synthesis (lathosterol and desmosterol) inversely reflected those of absorption (cholestanol and phytosterols) in PSC and controls (r-range -0.247 to -0.559, p < 0.01 for all), contrary to AH patients, among whom this reciprocal regulation was partially recovered on day 90 (lathosterol: r-range -0.733 to -0.952, p < 0.05 for all). AH patients had ~26% lower lathosterol/cholesterol, but 1.13-3.87-fold higher cholestanol/cholesterol and sitosterol/cholesterol compared to control groups (p < 0.05 for all). Median ferritin concentration at baseline was ~37% lower (p = 0.011) among the responders. Cholesterol precursors and phytosterols have a disease-specific profile in AH. Phytosterols and ferritin may serve as surrogate markers for short-term response.
-
4.
Postprandial plasma oxyphytosterol concentrations after consumption of plant sterol or stanol enriched mixed meals in healthy subjects.
Baumgartner, S, Mensink, RP, Konings, M, Schött, HF, Friedrichs, S, Husche, C, Lütjohann, D, Plat, J
Steroids. 2015;(Pt B):281-6
Abstract
Epidemiological studies have reported inconsistent results on the relationship between increased plant sterol concentrations with cardiovascular risk, which might be related to the formation of oxyphytosterols (plant sterol oxidation products) from plant sterols. However, determinants of oxyphytosterol formation and metabolism are largely unknown. It is known, however, that serum plant sterol concentrations increase after daily consumption of plant sterol enriched products, while concentrations decrease after plant stanol consumption. Still, we have earlier reported that fasting oxyphytosterol concentrations did not increase after consuming a plant sterol- or a plant stanol enriched margarine (3.0g/d of plant sterols or stanols) for 4weeks. Since humans are in a non-fasting state for most part of the day, we have now investigated effects on oxyphytosterol concentrations during the postprandial state. For this, subjects consumed a shake (50g of fat, 12g of protein, 67g of carbohydrates), containing no, or 3.0g of plant sterols or plant stanols. Blood samples were taken up to 8h and after 4h subjects received a second shake (without plant sterols or plant stanols). Serum oxyphytosterol concentrations were determined in BHT-enriched EDTA plasma via GC-MS/MS. 7β-OH-campesterol and 7β-OH-sitosterol concentrations were significantly higher after consumption of a mixed meal enriched with plant sterol esters compared to the control and plant stanol ester meal. These increases were seen only after consumption of the second shake, illustrative for a second meal effect. Non-oxidized campesterol and sitosterol concentrations also increased after plant sterol consumption, in parallel with 7β-OH concentrations and again only after the second meal. Apparently, plant sterols and oxyphytosterols follow the same second meal effect as described for dietary cholesterol. However, the question remains whether the increase in oxyphytosterols in the postprandial phase is due to absorption or endogenous formation.
-
5.
Comparable reduction in cholesterol absorption after two different ways of phytosterol administration in humans.
Amiot, MJ, Knol, D, Cardinault, N, Nowicki, M, Bott, R, Antona, C, Borel, P, Bernard, JP, Duchateau, G, Lairon, D
European journal of nutrition. 2013;(3):1215-22
Abstract
PURPOSE Consumption of phytosterols is a nutritional strategy to reduce cholesterol absorption, but the efficacy of various phytosterol intake modalities remains uncertain. The main objective was to investigate the effects of phytosterol esters (PE) provided either as a spread (dispersed in fat) during a mixed meal or as a minidrink (micro-dispersed in liquid form) after a meal. METHODS In a randomized, single-blinded crossover design, 12 healthy intubated volunteers tested three different liquid meal sequences with and without PE. The liquid meal (500 mL, Fortisip) contained an oral dose (80 mg) of deuterium-enriched cholesterol (D7C). The intubation was stopped at 240 min, and the fate of sterols was determined in the different phases of duodenal content samples as function of time. A second solid fat-containing meal without sterols was consumed at 270 min. D7C was quantified in chylomicrons and plasma for 8 h. The conditions tested were as follows: (1) no PE added (control), (2) PE in a spread added into a liquid meal (PE-spread meal) and (3) PE given 30 min after a liquid meal as 100-g yoghurt drink (PE-minidrink meal). RESULTS Addition of PE decreased the incorporation of cholesterol into the duodenum aqueous phase including micelles. PE added as a spread or as a minidrink significantly and comparably lowered meal cholesterol occurrence in chylomicrons (-40 % for PE-spread and -54 % for PE-minidrink, p < 0.0001) compared with the control meal. CONCLUSIONS PE either dispersed in fat during a meal or micro-dispersed in a liquid form after a meal resulted in a markedly reduced occurrence of meal-derived cholesterol in the circulation at a comparable extent.
-
6.
In vivo evaluation of a Poly-2p barrier cream protective effect.
Lembo, S, Lembo, C, Lo Conte, V, Gallo, L, La Bella, S, Martellotta, D, Ayala, F
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2010;(6):703-8
Abstract
AIM: Theoretically, skin barrier creams reduce or even prevent the penetration into the skin by building up a physical barrier, like a thin film between the skin and the irritant. Practically, controversial experiences concerning the effectiveness of barrier creams exist. For this, we propose an in vivo method to evaluate the efficacy of barrier creams trough clinical scoring and instrumental analysis. METHODS Nineteen housewives with hand dermatitis in remission phase were enrolled in the study. Every patient was evaluated clinically and an arbitrary score was assigned by the investigator considering erythema, exudation, lichenification and xerosis. A score was also assigned by every patient to itching and burning. As measurement of the functional state of the skin and of the effectiveness of the barrier cream, transepidermal water loss (TEWL), corneometry, colorimetry and visco-elasticity determination were performed. To investigate the protection properties against irritant products, the 24-h irritancy patch test with sodium lauryl sulphate 1% in water was used. RESULTS Through the patch test technique the efficacy of the barrier cream was tested compared to other topical products containing corticosteroids, lipids, humectants or urea, with already known anti-inflammatory, lenitive or protective properties. The results showed this methods easy and fast in handling, non-invasive, standardized, and in vivo applicable for evaluation and ranking of barrier creams. CONCLUSION The study preparation demonstrated high tolerability and indubitable efficacy in improving the skin barrier function even towards a very well known irritant.
-
7.
Very high plant stanol intake and serum plant stanols and non-cholesterol sterols.
Gylling, H, Hallikainen, M, Nissinen, MJ, Simonen, P, Miettinen, TA
European journal of nutrition. 2010;(2):111-7
Abstract
BACKGROUND Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored. AIM OF THE STUDY We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols. METHODS In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41-73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption. RESULTS When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% (P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 +/- 1 microg/dL, staest: 37 +/- 2 microg/dL, serum campestanol during intervention, controls: 0.5 +/- 0 microg/dL, staest: 9 +/- 1 microg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks. CONCLUSIONS Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2-3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.
-
8.
Effect of plant sterols in combination with other cholesterol-lowering foods.
Jenkins, DJ, Kendall, CW, Nguyen, TH, Marchie, A, Faulkner, DA, Ireland, C, Josse, AR, Vidgen, E, Trautwein, EA, Lapsley, KG, et al
Metabolism: clinical and experimental. 2008;(1):130-9
Abstract
The National Cholesterol Education Program Adult Treatment Panel III guidelines advocate effective combinations of cholesterol-lowering dietary components. This approach (dietary portfolio) produces large reductions in serum cholesterol, but the contribution of individual components remains to be established. We therefore assessed the effect of eliminating one out of the 4 dietary portfolio components. Plant sterols were selected because at 2 g/d, they have been reported to reduce low-density lipoprotein cholesterol (LDL-C) by 9% to 14%. Forty-two hyperlipidemic subjects were prescribed diets high in soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal) for 80 weeks. Subjects were instructed to take these together with plant sterols (1.0 g/1000 kcal) except between weeks 52 and 62. While taking the full dietary portfolio, including plant sterols, mean LDL-C reduction from baseline was 15.4% +/- 1.6% (P < .001). After sterol elimination, mean LDL-C reduction was 9.0% +/- 1.5% (P < .001). Comparable LDL-C reductions were also seen for the 18 subjects with a complete data set: on plant sterols, 16.7% +/- 3.1% (P < .001) and off plant sterols, 10.3% +/- 2.6% (P < .001), resulting in a 6.3% +/- 2.0% (P = .005) difference attributable to plant sterols. Compliance in this group of 18 was 67.0% +/- 5.9% for plant sterols and 61.9% +/- 4.8% for the other components. In combination with other cholesterol-lowering foods and against the background of a low-saturated fat diet, plant sterols contributed over one third of the LDL-C reduction seen with the dietary portfolio after 1 year of following dietary advice.
-
9.
Respective hydrolysis and esterification of esterified and free plant stanols occur rapidly in human intestine after their duodenal infusion in triacyl- or diacylglycerol.
Nissinen, MJ, Vuoristo, M, Gylling, H, Miettinen, TA
Lipids. 2007;(7):603-12
Abstract
Esterification of dietary phytosterols and glycerols may affect intestinal absorption of cholesterol and non-cholesterol sterols. We infused plant stanol esters in triacylglycerol (TAG) (F1) and diacylglycerol (DG) (F2) oils, and free plant stanols in F1 and F2 (F3) to the duodenum of healthy human subjects and sampled the contents from the proximal jejunum (PJ). Free and ester sterols were analysed from the infusates, and intestinal contents before and after ultracentrifuge separation of oil, micelle and sediment phases. During the 60-cm intestinal passage, over 40% of plant stanol esters were hydrolysed (P < 0.05) but around 30% of the infused free plant stanols (P < 0.05) and up to 40% of cholesterol (P < 0.05) were esterified in PJ after infusions. TAG in F1 favoured accumulation of plant stanol esters in the oil phase of the PJ aspirates as compared with respective values of F2 and F3 (P < 0.05 for both). About one third of free plant stanols of F3 had been esterified (P < 0.05) and 17% precipitated mainly in free form in the PJ aspirates (P < 0.05 compared with F1 and F2). In conclusion, DG- and TAG-oils had no profound superiority over each other as intestinal carriers regarding hydrolysis/esterification of administered plant stanol esters and cholesterol and their partition in oil, micellar and sediment phases in the PJ. The unesterified plant stanols experienced partial esterification and sedimentation during their intestinal passage, which might influence their biochemical properties in that segment of the gut where cholesterol is absorbed.
-
10.
Effect of plant sterols and endurance training on LDL particle size and distribution in previously sedentary hypercholesterolemic adults.
Varady, KA, St-Pierre, AC, Lamarche, B, Jones, PJ
European journal of clinical nutrition. 2005;(4):518-25
Abstract
BACKGROUND Plant sterols and exercise favourably alter lipid profiles in a way that protect against future coronary heart disease (CHD). However, their effects on other indicators of CHD risk, such as LDL particle size, still need further clarification. OBJECTIVE This study examined the effect of plant sterols, exercise, and the combination of plant sterols and exercise, on LDL particle size and distribution in previously sedentary, hypercholesterolemic adults. DESIGN In an 8-week, placebo-controlled, parallel-arm clinical trial, 84 subjects were randomized to one of four intervention groups: (1) combination of sterols and exercise, (2) exercise, (3) sterol, or (4) control. RESULTS Exercise significantly (P < 0.05) reduced post-treatment LDL peak particle size from 255 to 253 A. Additionally, exercise significantly (P < 0.05) decreased the proportion of large LDL particles within plasma. Sterol supplementation significantly (P < 0.05) decreased the estimated cholesterol concentrations within small, medium, and large LDL particles by 13.4, 13.5, and 14.4%, respectively, yet had no effect on the distribution of cholesterol among various LDL particle sizes. Furthermore, decreased body weight post-training was associated with increased cholesterol in small LDL particles (r = -0.52, P < 0.0001). Decrease in body fat percent (BF%) post-training was associated with increased cholesterol concentrations in small LDL particles (r = -0.29, P < 0.01). CONCLUSION On the basis of modulating LDL electrophoretic characteristics, the present study demonstrates that plant sterols have no effect on CHD risk, while short-term exercise may potentially increase CHD risk by decreasing LDL peak particle size. SPONSORSHIP This study was sponsored by The Heart and Stroke Foundation of Canada.