Plant Sterols (Phytosterols) | Supplementopedia

Overview

Plant sterols, also called phytosterols, are a group of naturally occurring, plant‑derived sterols and stanols that structurally resemble cholesterol.
The primary purpose of dietary phytosterols is to modulate lipid metabolism, most notably by reducing intestinal absorption of dietary cholesterol, thereby supporting cardiovascular health.

Daily intake of 1.5–2.5 g of phytosterols can lower LDL‑cholesterol by 8–12 % without affecting HDL‑cholesterol or triglycerides, as shown in extensive randomized controlled trials.
This LDL‑cholesterol reduction translates into modest reductions in cardiovascular‑disease risk when combined with a heart‑healthy diet.
Meta‑analyses suggest modest improvements in post‑prandial glucose excursions and insulin sensitivity, supporting metabolic health.
Emerging evidence indicates that phytosterols may modestly reduce inflammatory markers (e.g., CRP) and improve endothelial function, although effects on cognition or physical performance are not consistently demonstrated.
The most robust and clinically relevant benefit is the LDL‑cholesterol‑lowering effect, which is recognized by the FDA (health claim) and EFSA (health claim) for cardiovascular risk reduction.

Phytosterols compete with dietary and biliary cholesterol for incorporation into mixed micelles in the intestinal lumen due to their similar sterol backbone but higher hydrophobicity.
This competition reduces the solubilization of cholesterol, decreasing its incorporation into micelles and consequently its absorption across the enterocyte brush‑border via the NPC1L1 transporter.
The unabsorbed cholesterol is excreted in feces.
Within enterocytes, the limited cholesterol influx up‑regulates LDL‑receptor expression in the liver via SREBP‑2, enhancing clearance of circulating LDL particles.
Additionally, phytosterols may modestly inhibit HMG‑CoA reductase activity and modulate bile acid synthesis, further contributing to lower serum LDL.
Their anti‑inflammatory and antioxidant properties are thought to arise from modulation of NF‑κB signaling and reduction of oxidative LDL, but these pathways are less well quantified.

The most studied and effective dose range for cholesterol‑lowering is 1.5–2.5 g of total phytosterols per day, typically delivered as a blend of β‑sitosterol, campesterol, and stigmasterol.
A single 2 g dose taken with a main meal (preferably containing some fat) maximizes micellar competition; split dosing (e.g., 1 g with breakfast and 1 g with dinner) yields similar efficacy.
For individuals targeting modest LDL reductions, 1 g per day may still provide a 3–4 % reduction.
Individuals on cholesterol‑lowering drugs (statins, ezetimibe) can use the same dosage, but clinicians often monitor LDL to avoid overly low values.
In children, doses are weight‑adjusted (≈0.5 g/70 kg) and limited to ≤1 g/day, per pediatric guidelines.

Phytosterols are generally well tolerated; the most common adverse events are mild gastrointestinal symptoms (flatulence, bloating, or stool softening) occurring in ≤10 % of users.
No significant effects on fat‑soluble vitamin (A, D, E, K) absorption have been reported at typical doses, though very high intakes (>3 g/day) may modestly reduce carotenoid absorption.
Contraindications include sitosterolemia (a rare autosomal recessive disorder) where phytosterol accumulation is pathogenic.
Caution is advised for pregnant or lactating women; while no adverse outcomes have been reported, most guidelines recommend limiting intake to <2 g/day and consulting a health professional.
No clinically relevant interactions with statins, fibrates, or ezetimibe have been observed, but concurrent use may amplify LDL‑cholesterol reductions, warranting periodic lipid monitoring.

Phytosterols are tetracyclic triterpenoid alcohols (C27–C29) with a characteristic cyclopentanoperhydrophenanthrene nucleus, a side‑chain at C‑17, and a methyl group at C‑24.
The most abundant member, β‑sitosterol, has the formula C₂₉H₅₀O and the IUPAC name (3β,24R)-Stigmast-5-en-3-ol.
Other common phytosterols include campesterol (C₂₈H₄₈O) and stigmasterol (C₂₉H₄₈O).
They are highly lipophilic (log P ≈ 7–8) and poorly soluble in water but readily dissolve in oils and lipid membranes.
Their structural similarity to cholesterol (identical sterol nucleus) underlies their competitive absorption, while the additional ethyl or methyl groups at C‑24 confer a slightly larger steric bulk, reducing membrane permeability and favoring excretion.

Commercial phytosterols are extracted primarily from plant oils (e.g., soybean, corn, and canola) and wheat germ by solvent extraction (hexane or supercritical CO₂) followed by crystallization or chromatography to enrich the sterol fraction.
Tall oil (a by‑product of the pulp and paper industry) is another industrial source, especially for β‑sitosterol.
Proprietary processes may use enzymatic esterification to improve solubility in food matrices.
For supplements, the phytosterol content is expressed as “total phytosterols” (including free sterols and sterol esters).
High‑quality products are ≥ 90 % purity, free of heavy metals, pesticides, and trans‑fat contaminants.
Standardized extracts must comply with pharmaco‑peia specifications (e.g., USP, European Pharmacopeia) and be tested for oxidative stability (e.g., peroxide value) to ensure efficacy and safety.