Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants

Baumgartner, Sabine; Ras, Rouyanne T.; Trautwein, Elke A.; Konings, Maurice; Mensink, Ronald P.

doi:10.1194/jlr.ra119000274

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…There is no clear explanation for this discrepancy, which might be caused by differences in the background diet of the study population. More recently, Fuhrmann et al [37] and Baumgartner et al [38] showed that the mean POP concentrations in two large cohorts (400‒500 subjects) were 22‒33 nmol/L, which is within the range of the data obtained in our study. These studies [37,38] further showed that none of the investigated POP, except for 7α-OH-campesterol and the 7α-OH-campesterol-to-cholesterol ratio in the Fuhrmann et al [37] study, showed an association with cardiovascular events.…”

Section: Discussionsupporting

confidence: 90%

Serum Concentration of Plant Sterol Oxidation Products (POP) Compared to Cholesterol Oxidation Products (COP) after Intake of Oxidized Plant Sterols: A Randomised, Placebo-Controlled, Double-Blind Dose–Response Pilot Study

et al. 2019

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Plant sterols (PS) are oxidized to PS oxidation products (POP). This study quantified the change in serum POP compared to cholesterol oxidation products (COP) after the intake of increasing POP doses. This was a double-blind, randomized, placebo-controlled, dose‒response pilot study with healthy individuals in four groups (15 per group). The control group received products with no added PS or POP and treatment groups received daily 20–25 g margarine with added PS (mean 3 g/d) and two cookies (~28 g) for six weeks. Cookies delivered 8.7 (low-dose), 15.2 (medium-dose), or 37.2 (high-dose) mg/d POP. Fasting serum POP and COP were measured at the baseline, days 14, 28, and 42 in all participants and days 7, 21, and 35 in a subset. Sixty individuals completed the study; 52 were included in per protocol analysis. Serum POP increased with increasing POP intake and plateaued at dose >15 mg/d. Stabilized POP concentrations were (mean ± SD) 38.9 ± 6.9, 91.0 ± 27.9, 144.4 ± 37.9 and 203.0 ± 63.7 nmol/L, for control, low-, medium-, and high-dose POP groups, respectively. For all groups, the serum COP ranged from 213 to 262 nmol/L and the average POP/COP ratio was <1. Serum POP concentrations increased non-linearly, reaching stabilized concentrations in <7 days, and remained below COP concentrations after the intake of increasing POP doses.

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Section: Discussionsupporting

confidence: 90%

Serum Concentration of Plant Sterol Oxidation Products (POP) Compared to Cholesterol Oxidation Products (COP) after Intake of Oxidized Plant Sterols: A Randomised, Placebo-Controlled, Double-Blind Dose–Response Pilot Study

et al. 2019

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“…While some studies have shown a positive association between campesterol or absorption marker levels and cardiovascular risk, 28 , 29 , 30 others have reported conflicting results. 31 , 32 , 33 A study demonstrated that plasma campesterol was positively associated with carotid plaques in asymptomatic subjects. 28 Another study found that the combined reduction of campesterol and lathosterol predicts future cardiac events in patients with early‐stage nonischemic dilated cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

“… 30 In the Framingham Offspring Study, campesterol, sitosterol, and cholestanol were associated with coronary artery disease, while lathosterol was negatively related to the coronary disease. 31 However, contrasting results have been reported regarding the relationship between cholesterol absorption and synthesis markers and CVEs. Campesterol and sitosterol were unrelated to coronary artery disease in the EPIC‐Norfolk (European Prospective Investigation Into Cancer–Norfolk) cohort study.…”

Section: Discussionmentioning

confidence: 99%

Higher Cholesterol Absorption Marker at Baseline Predicts Fewer Cardiovascular Events in Elderly Patients Receiving Hypercholesterolemia Treatment: The KEEP Study

Kuwabara,

Sasaki,

Ouchi

et al. 2024

JAHA

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Background Higher cholesterol absorption has been reported to be related to a higher incidence of cardiovascular events (CVEs). The KEEP (Kyushu Elderly Ezetimibe Phytosterol) study, a substudy of the EWTOPIA 75 (Ezetimibe Lipid‐Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older) study, investigated the relationships of cholesterol absorption and synthesis markers with CVEs in older old individuals with hypercholesterolemia, particularly in relation to ezetimibe treatment. Methods and Results Eligible patients were those aged ≥75 years who had low‐density lipoprotein cholesterol ≥140 mg/dL, no history of coronary artery disease, and no recent use of lipid‐lowering drugs. Participants were randomly assigned into a diet‐only or diet‐plus‐ezetimibe group. Baseline and 24‐week follow‐up blood samples were analyzed for cholesterol absorption (eg, campesterol) and synthesis markers (eg, lathosterol). Of 1287 patients, 1061 patients with baseline measurement were analyzed. Over a median follow‐up of 4.0 years, 64 CVEs occurred. Higher campesterol levels at baseline were significantly associated with a lower risk of CVEs. After adjustment for sex, age, and treatment, the hazard ratios for the lowest to highest quartile categories of baseline campesterol were 1.00 (reference), 0.59 (95% CI, 0.30–1.17), 0.44 (95% CI, 0.21–0.94), and 0.44 (95% CI, 0.21–0.93), respectively (trend P =0.01). This association persisted after further adjustment for hypertension, diabetes, and other cardiovascular risk factors. Neither interactions with ezetimibe treatment nor mediating effects of the changes in cholesterol absorption markers were observed. Conclusions The KEEP study indicated that higher campesterol levels without lipid‐lowering drugs were associated with a lower incidence of CVEs in older old individuals with hypercholesterolemia who were subsequently treated with diet or ezetimibe. Registration URL: https://www.umin.ac.jp ; unique identifier: UMIN000017769.

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“…GC-MS/MS has also been scarcely utilized for the quantitative analysis of POPs. Both hydroxyl and keto forms of sitosterol and campesterol oxidation products were identified and quantified in human serum [ 67 , 68 ]. The concentrations of POPs were found to increase after consuming phytosterol-enriched food.…”

Section: Analysis Of Phytosterol Oxidation Productsmentioning

confidence: 99%

Analytical Strategies to Analyze the Oxidation Products of Phytosterols, and Formulation-Based Approaches to Reduce Their Generation

2021

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Phytosterols are a class of lipid molecules present in plants that are structurally similar to cholesterol and have been widely utilized as cholesterol-lowering agents. However, the susceptibility of phytosterols to oxidation has led to concerns regarding their safety and tolerability. Phytosterol oxidation products (POPs) present in a variety of enriched and non-enriched foods can show pro-atherogenic and pro-inflammatory properties. Therefore, it is crucial to screen and analyze various phytosterol-containing products for the presence of POPs and ultimately design or modify phytosterols in such a way that prevents the generation of POPs and yet maintains their pharmacological activity. The main approaches for the analysis of POPs include the use of mass spectrometry (MS) linked to a suitable separation technique, notably gas chromatography (GC). However, liquid chromatography (LC)-MS has the potential to simplify the analysis due to the elimination of any derivatization step, usually required for GC-MS. To reduce the transformation of phytosterols to their oxidized counterparts, formulation strategies can theoretically be adopted, including the use of microemulsions, microcapsules, micelles, nanoparticles, and liposomes. In addition, co-formulation with antioxidants, such as tocopherols, may prove useful in substantially preventing POP generation. The main objectives of this review article are to evaluate the various analytical strategies that have been adopted for analyzing them. In addition, formulation approaches that can prevent the generation of these oxidation products are proposed.

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Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants

Abstract: Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants.

Cited by 8 publications

References 38 publications

Serum Concentration of Plant Sterol Oxidation Products (POP) Compared to Cholesterol Oxidation Products (COP) after Intake of Oxidized Plant Sterols: A Randomised, Placebo-Controlled, Double-Blind Dose–Response Pilot Study

Serum Concentration of Plant Sterol Oxidation Products (POP) Compared to Cholesterol Oxidation Products (COP) after Intake of Oxidized Plant Sterols: A Randomised, Placebo-Controlled, Double-Blind Dose–Response Pilot Study

Higher Cholesterol Absorption Marker at Baseline Predicts Fewer Cardiovascular Events in Elderly Patients Receiving Hypercholesterolemia Treatment: The KEEP Study

Analytical Strategies to Analyze the Oxidation Products of Phytosterols, and Formulation-Based Approaches to Reduce Their Generation

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