Non-cholesterol sterols are validated biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis. However, their use in metabolic disturbances has not been systematically explored. Therefore, we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders. Potentially relevant studies were retrieved by a systematic search of three databases in July 2018 and ninety-four human studies were included. Cholesterol-standardized levels of campesterol, sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis. Their use as biomarkers was examined in the following metabolic disorders: overweight/obesity (n = 16), diabetes mellitus (n = 15), metabolic syndrome (n = 5), hyperlipidemia (n = 11), cardiovascular disease (n = 17), and diseases related to intestine (n = 16), liver (n = 22) or kidney (n = 2). In general, markers for cholesterol absorption and synthesis displayed reciprocal patterns, showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis. Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified, suggesting that metabolic disorders can be classified as ‘cholesterol absorbers or cholesterol synthesizers’. Future studies should be performed to confirm or refute these findings and to examine whether this information can be used for targeted (dietary) interventions.

A wealth of data demonstrates a causal link between serum low-density lipoprotein cholesterol (LDL-C) concentrations and cardiovascular disease (CVD). Any decrease in serum LDL-C concentrations is associated with a decreased CVD risk, and this benefit is similar to a comparable LDL-C reduction after drug treatment and dietary intervention. Moreover, life-long reductions in serum LDL-C levels have a large impact on CVD risk and a long-term dietary enrichment with functional foods or supplements with a proven LDL lowering efficacy is therefore a feasible and efficient approach to decrease future CVD risk. Functional foods with an LDL-C lowering effect can improve health and/or a reduce the risk of disease. However, it has not been mentioned specifically whether this concerns mainly universal prevention or whether this can also be applied to the hierarchy towards care related prevention. Therefore, we here describe the effects of a list of interesting functional food ingredients with proven benefit in LDL-C lowering. In addition, we pay particular attention to the emerging evidence that the addition of these functional ingredients and supplements is advisable as universal and selective prevention in the general population. Moreover, functional ingredients and supplements are also helpful in care related prevention, i.e. in patients with elevated LDL-C concentrations who are statin-intolerant or are not able to achieve their LDL-C target levels. Furthermore, we will highlight practical aspects regarding the use of functional foods with an LDL-C lowering effect, such as the increasing importance of shared decision making of medical doctors and dieticians with patients to ensure proper empowerment and better adherence to dietary approaches. In addition, we will address costs issues related to the use of these functional foods, which might be a barrier in some populations.

Purpose Plant sterols and stanols interfere with intestinal cholesterol absorption, and it has been questioned whether absorption and plasma concentrations of fat-soluble vitamins and carotenoids are also affected. We conducted a meta-analysis to assess the effects of plant sterol and stanol consumption on plasma fat-soluble vitamin and carotenoid concentrations. Methods Forty-one randomized controlled trials involving 3306 subjects were included. Weighted absolute and relative changes of non-standardized and total cholesterol (TC)-standardized values (expressed as summary estimates and 95 % CIs) were calculated for three fat-soluble vitamins (α- and γ-tocopherol, retinol and vitamin D) and six carotenoids (β-carotene, α-carotene, lycopene, lutein, zeaxanthin and β-cryptoxanthin) using a random effects model. Heterogeneity was assessed using predefined subject and treatment characteristics. Results Average plant sterol or stanol intake was 2.5 g/d. Relative non-standardized and TC-standardized concentrations of β-carotene decreased by, respectively, −16.3 % (95 % CI −18.3; −14.3) and −10.1 % (−12.3; −8.0), α-carotene by −14.4 % (−17.5; 11.3) and −7.8 % (−11.3; −4.3), and lycopene by −12.3 % (−14.6; −10.1) and −6.3 % (−8.6; −4.0). Lutein concentrations decreased by −7.4 % (−10.1; −4.8), while TC-standardized concentrations were not changed. For zeaxanthin, these values were −12.9 % (−18.9; −6.8) and −7.7 % (−13.8; −1.7) and for β-cryptoxanthin −10.6 % (−14.3; −6.9) and −4.8 % (−8.7; −0.9). Non-standardized α-tocopherol concentrations decreased by −7.1 % (−8.0; −6.2) and γ-tocopherol by −6.9 % (−9.8; −3.9), while TC-standardized tocopherol concentrations were not changed. Non-standardized retinol and vitamin D concentrations were not affected. Results were not affected by baseline concentrations, dose, duration and type of plant sterols/stanols, except for significant effects of duration (≤4 vs. >4 weeks) on TC-standardized lutein concentrations (1.0 vs. −5.6 %) and type of plant sterol/stanol on TC-standardized β-carotene concentrations (−8.9 vs. −14.2 %). Conclusions Plant sterol and stanol intake lowers TC-standardized hydrocarbon carotenoid concentrations, differently affects TC-standardized oxygenated carotenoid concentrations, but does not affect TC-standardized tocopherol concentrations or absolute retinol and vitamin D concentrations. Observed concentrations remained within normal ranges.

Despite increased serum plant sterol concentrations after consumption of plant sterol enriched margarines, plasma oxyphytosterol concentrations were not increased in healthy subjects. Here, we assessed plasma oxyphytosterol concentrations and whether they are affected by antioxidants in subjects with elevated oxidative stress. Twenty subjects with impaired glucose tolerance (IGT) or type 2 diabetes (DM2) consumed for 4 weeks placebo, vitamin E (804 mg/d) or lipoic acid capsules (600 mg/d). Plasma and blood cell oxyphytosterol and oxycholesterol concentrations were determined in butylated hydroxytoluene-enriched EDTA plasma via GC-MS. Also, markers reflecting oxidative stress and antioxidant capacity were measured. Plasma oxycampesterol and oxysitosterol concentrations were 122% and 83% higher in IGT or DM2 subjects than in healthy subjects, as determined in an earlier study. Vitamin E or lipoic acid supplementation did not reduce plasma oxyphytosterol and oxycholesterol concentrations, or other markers reflecting oxidative stress or antioxidative capacity. Concentrations of different oxyphytosterols correlated within plasma, and within red blood cells and platelets. However, plasma and blood cell oxyphytosterol levels did not correlate. Although plasma oxyphytosterol concentrations are higher in IGT or DM2 subjects than in healthy subjects, 4-weeks vitamin E or lipoic acid supplementation does not lower plasma oxycholesterol or oxyphytosterol concentrations.