# Phytosterols and phytostanols: micelles, NPC1L1 and ABCG5/G8

- Canonical: https://nutrifit.health/knowledge/phytosterols-phytostanols-npc1l1-cholesterol-absorption
- Language: en
- Published: 2026-10-08T15:58:24.017Z
- Updated: 2026-10-08T15:58:24.017Z
- Author: NutriFit Editorial

> Plant sterol chemistry, mixed-micelle competition, NPC1L1 uptake, ABCG5/G8 efflux and hepatic feedback. LDL-C findings, sitosterolemia, combinations, formulation and the limits of clinical safety evidence.

Phytosterols are plant lipids structurally related to cholesterol. Their analogues with a saturated C5=C6 bond are called phytostanols. Adding them to the diet can reduce intestinal cholesterol absorption and low-density lipoprotein cholesterol (LDL-C). A lower laboratory value, however, does not establish prevention of myocardial infarction. This article connects sterol chemistry, micellar physics, cellular transport and clinical findings while distinguishing experimental models from conclusions in humans.

## 1. Plant biosynthesis and the dietary sterol pool

Animals and plants use squalene-2,3-epoxide as a sterol precursor. Animal lanosterol synthase and higher-plant cycloartenol synthase direct cyclization along different pathways. In plants, S-adenosylmethionine supplies methyl groups to sterol C-methyltransferases SMT1/SMT2, and side-chain modifications generate diverse phytosterols. This distinction does not mean that every plant is entirely cholesterol-free or that all eukaryotes share one pathway.

Sterols insert into phospholipid bilayers: the hydroxyl interacts with the polar region, while the rings and side chain lie among acyl chains. They modify packing, permeability and membrane phase behavior. Liquid-ordered and liquid-disordered phases can coexist in model membranes. Living-cell microdomains are dynamic; explaining them solely through an ideally flat sterol skeleton would oversimplify their biology. The relation between membrane composition and lipid damage is discussed in the article on [astaxanthin and membrane oxidation](/knowledge/astaxanthin-membrane-cross-linking-lipid-peroxidation).

Vegetable oils, nuts, seeds, cereals and legumes contain free sterols, esters and glycosides. Habitual intake is measured in hundreds of milligrams, whereas many enriched-food studies use gram quantities. Intestinal plant sterols encounter both dietary cholesterol and cholesterol secreted in bile. Their mechanism therefore remains relevant when dietary cholesterol intake is low: the biliary pool still matters.

Sitosterol's cholesterol-lowering effects have been investigated since the mid-twentieth century. Incorporating stanol esters into a food fat matrix was a practical advance. In the year-long randomized trial by Miettinen et al. (1995), stanol-ester margarine lowered LDL-C; the trial assessed blood lipids, rather than cardiovascular events. Subsequent discoveries of ABCG5/ABCG8 and NPC1L1 explained why chemically similar sterols have different absorption.

## 2. Chemical structure and limits of physicochemical comparisons

The common steroid skeleton contains three six-membered and one five-membered ring. Common sterols have a 3β-hydroxyl group and a side chain at C17. Cholesterol contains 27 carbons. Campesterol's C24 methyl and β-sitosterol's C24 ethyl increase the carbon count to 28 and 29 respectively. Stigmasterol has an additional trans C22=C23 double bond; brassicasterol combines C24 methylation with this unsaturation.

| Compound | Formula | Molar mass, g/mol | Principal distinction |
| --- | --- | --- | --- |
| Cholesterol | $C_{27}H_{46}O$ | 386.7 | C5=C6; no additional C24 alkyl |
| Campesterol | $C_{28}H_{48}O$ | 400.7 | C24 methyl |
| β-Sitosterol | $C_{29}H_{50}O$ | 414.7 | C24 ethyl |
| Stigmasterol | $C_{29}H_{48}O$ | 412.7 | C24 ethyl and C22=C23 |
| Brassicasterol | $C_{28}H_{46}O$ | 398.7 | C24 methyl and C22=C23 |
| Campestanol | $C_{28}H_{50}O$ | 402.7 | Saturated 5α analogue of campesterol |
| Sitostanol | $C_{29}H_{52}O$ | 416.7 | Saturated 5α analogue of sitosterol |

Reducing C5=C6 changes the A/B ring junction and local conformations, but does not flatten every ring: saturated six-membered rings retain three-dimensional conformations. C22=C23 restricts rotation about that bond; other side-chain bonds remain mobile. R/S assignments depend on substituent priorities and cannot be replaced with a universal rule that every plant sterol is 24R.

All these compounds dissolve poorly in water. Additional alkyl groups affect lipophilicity, crystal packing and membrane interactions. Nevertheless, octanol/water $\log P$, aqueous solubility, monolayer molecular area and bile-micelle solubility are different properties. Values depend on the method, temperature, crystal form and medium. A calculated $\log P$ does not yield a universal “3.5-fold micellar affinity” or a clinical LDL-C reduction. The table consequently retains verifiable structural comparisons without treating unsupported constants as a unified experimental matrix.

## 3. Mixed micelles: partitioning, competition and precipitation

During fat digestion, bile salts, phosphatidylcholine and lysophospholipids, fatty acids and monoacylglycerols form mixed aggregates. Pancreatic lipase with colipase hydrolyzes triacylglycerols; phospholipase A2 contributes to phospholipid digestion. Micelles, vesicles, emulsion droplets and other phases coexist in intestinal contents. There is no single micelle diameter, critical micellar concentration or sterol/bile-salt ratio applicable to every meal.

Micellar solubilization makes hydrophobic sterols more available near the brush border. The unstirred water layer creates diffusion resistance. A micelle need not enter the enterocyte intact: sterols can exchange between aggregates, aqueous surroundings and membranes. Both exchange rates and aggregate capacity reflect molecular packing as well as hydrophobicity.

Armstrong and Carey (1987) measured equilibrium solubility of different sterols in defined bile-salt solutions. Mel'nikov et al. (2004) investigated dietary mixed micelles in vitro. These experiments support structure-dependent solubilization and competition, but do not demonstrate an inevitable human sequence in which sitostanol always has the highest affinity and all displaced cholesterol immediately crystallizes.

Transfer thermodynamics can be expressed as:

$$
\Delta G^\circ_{\mathrm{transfer}}=\mu^\circ_{\mathrm{micelle}}-\mu^\circ_{\mathrm{water}}=-RT\ln K_p
$$

Here $\mu^\circ$ is standard chemical potential, $R$ the gas constant, $T$ absolute temperature in kelvin, and $K_p$ a dimensionless partition constant with consistently defined standard states. A negative $\Delta G^\circ$ indicates preference for the micellar environment under those conditions. This is not an individual's supplement response; $K_p$ does not automatically equal octanol/water $P$.

If dissolved cholesterol exceeds the equilibrium solubility of a specified phase, supersaturation is possible:

$$
S=\frac{C}{C_{\mathrm{sat}}}
$$

$C$ and $C_{\mathrm{sat}}$ use the same units; $S>1$ denotes supersaturation. Precipitation, co-crystallization and cholesterol-monohydrate formation are physically possible, but their kinetics depend on composition and time. Crystallization in model bile is not an obligatory clinically established step of every intestinal phytosterol response. The supported practical conclusion is more limited: phytosterols reduce cholesterol availability for uptake and increase elimination of unabsorbed sterols. Microbiota can convert some cholesterol to coprostanol.

In Racette et al. (2010), 18 adults completed controlled crossover feeding periods with different phytosterol intakes, four weeks each. Compared with 59 mg/day, 459 and 2059 mg/day increased fecal cholesterol elimination and reduced absorption; LDL-C fell significantly at the highest intake. This directly examined sterol balance, but does not define a fixed 40–60% absorption reduction for all products and individuals.

## 4. NPC1L1: sterol capture, domains and endocytosis

The NPC1L1 gene lies at 7p13 and contains 20 exons. Alternative splicing generates different isoforms, so the length of one sequence should not be assigned to every experimental construct. The overall architecture contains more than 1300 amino acids and 13 transmembrane segments.

NPC1L1 resides on the apical enterocyte surface. The human protein has over 1300 amino acids and 13 transmembrane segments, a sterol-sensing region and large extracellular N-terminal, middle and C-terminal domains. Altmann et al. (2004) demonstrated its critical role in cholesterol absorption using knockout mice. Davis et al. (2004) showed involvement in phytosterol uptake as well. The process should not be described as completely indiscriminate: several sequential barriers determine systemic exposure.

The N-terminal domain (NTD) contains a sterol-binding cavity. Structure 3QNT characterizes the human NTD. Dissociation constants and residue lists require identification of the actual protein, ligand and method; universal cholesterol and β-sitosterol values are not assigned to every structure here.

Huang et al. (2020) obtained cryo-EM structures of rat NPC1L1: apo 6V3F and 6V3H with the potent analogue ezetimibe-PS. In the open form, the NTD cavity is accessible; an approximately 60° NTD rotation connects it to an internal tunnel. The inhibitor analogue obstructs this route. The “closed” domain arrangement therefore does not mean the tunnel is absent: it forms but contains the inhibitor. The study supports a membrane-delivery model, rather than directly observing every human absorption step.

Ge et al. (2008) linked NPC1L1-mediated uptake to clathrin endocytosis in a cellular system. Li et al. (2014) identified **Numb** as the adaptor recognizing the C-terminal YVNXXF motif and participating in recruitment of clathrin/AP-2 machinery. Assigning direct universal motif recognition solely to AP-2 μ2 would be inaccurate. Membrane delivery, endocytosis and recycling of NPC1L1 are related but distinct, with model-dependent contributions. Ezetimibe interacts with NPC1L1 and reduces absorption; structural findings do not imply that all cellular vesicle formation stops.

Human NPC1L1 also occurs in hepatocyte canalicular membranes. Temel et al. (2007) studied its influence on biliary cholesterol, including in a transgenic model. This difference between human liver and conventional mouse models matters for translation.

[![NPC1L1 takes individual sterols into the enterocyte; ATP-dependent ABCG5/G8 exports them to the lumen; chylomicrons enter lymph.](https://api.nutrifit.health/api/v2/public/knowledge/files/images/nutrifit-scientific-20261002-phytosterols-phytostanols-npc1l1-cholesterol-absorption-transport-en-v1.png)](https://api.nutrifit.health/api/v2/public/knowledge/files/images/nutrifit-scientific-20261002-phytosterols-phytostanols-npc1l1-cholesterol-absorption-transport-en-v1.png)

## 5. ABCG5/ABCG8: reverse flux and separate compartments

Adjacent ABCG5 and ABCG8 genes on chromosome 2p21 encode half-transporters with N-terminal nucleotide-binding and C-terminal transmembrane domains. Heterodimerization is required for trafficking and function. The complex occupies apical enterocyte and canalicular hepatocyte membranes. Export goes into the intestinal lumen in the former and bile in the latter; these directions must be kept distinct.

Lee et al. (2016) determined nucleotide-free human ABCG5/G8 structure 5DO7 at 3.9 Å resolution. Six transmembrane helices per subunit form the transport complex. The two composite nucleotide sites are catalytically unequal: structural and functional data indicate asymmetry rather than two identical active ATPases. ATP binding and hydrolysis couple to membrane-domain rearrangements. The simplified reaction $ATP+H_2O\rightarrow ADP+P_i$ describes energy supply but does not establish a fixed two-ATP-per-sterol stoichiometry.

The complex exports cholesterol as well as plant sterols. Exclusive recognition of a “foreign” C24 alkyl through a single static pocket remains an oversimplification. Genetic and functional experiments establish its protective role: loss of function markedly increases phytosterol accumulation. Repa et al. (2002) demonstrated LXR-mediated expression regulation; Yu et al. (2002) found increased biliary secretion and reduced absorption with overexpression in mice. Neither establishes a universal threefold human phytosterol export rate.

After enterocyte entry, some cholesterol is esterified by SOAT2/ACAT2 and incorporated into ApoB-48-containing chylomicrons with MTP participation. Chylomicrons enter lymph and subsequently blood; their remnants deliver lipids to the liver. A small absorbed phytosterol fraction also reaches the liver, where canalicular ABCG5/G8 provides a second export barrier. Low plasma levels reflect both limited absorption and effective elimination, rather than absolutely absent transport.

Cholesterol is generally absorbed much more efficiently than plant sterols; campesterol is often absorbed better than sitosterol, and stanols less well still. Exact percentages depend on the molecule and measurement. Salen et al. (1970) found sitosterol absorption of up to 5% of intake versus 45–54% for cholesterol. Thus “all phytosterols strictly below 1%” is incorrect. Concentrations expressed in micromoles per liter likewise cannot be called submicromolar when they exceed one micromole per liter.

## 6. Sitosterolemia: failure of the protective barrier

Biallelic pathogenic variants in ABCG5 or ABCG8 cause autosomal recessive sitosterolemia. Berge et al. (2000) and Lu et al. (2001) linked the disease to these adjacent genes. Both intestinal export and biliary elimination are impaired. Manifestations vary: xanthomas, premature atherosclerosis, hemolysis, stomatocytosis, large platelets and thrombocytopenia occur in different combinations. Cholesterol can be elevated, sometimes substantially; a normal routine lipid result does not exclude the condition.

Routine lipids do not replace plant-sterol measurements by gas or liquid chromatography with mass spectrometry. Genetic testing clarifies suspected disease. Sterol incorporation into blood-cell membranes helps explain hematological findings, but experimental eNOS, NLRP3 and ER-stress pathways should not be presented as one established cause of every premature vascular event.

Specialist management includes limiting excess dietary sterols and reducing absorption, including with ezetimibe. A diet containing no sterol molecules is impractical. In the randomized Salen et al. (2004) trial, 37 patients received ezetimibe 10 mg/day or placebo; active treatment reduced sitosterol by 21% and campesterol by 24% after eight weeks. This is neither a guaranteed 70–85% response nor proof of resolving every blood-cell abnormality or preventing infarction. Sterol/stanol-enriched products are unsuitable in confirmed sitosterolemia. A single heterozygous variant requires individual interpretation and is not automatically equivalent to biallelic disease.

## 7. Hepatic feedback: SCAP, SREBP-2 and LDL receptors

Lower delivery of absorbed cholesterol can alter the regulated hepatic pool. SCAP escorts the membrane transcription factor SREBP-2; when sterol availability is sufficient, INSIG retains the complex in the endoplasmic reticulum (ER). Falling accessible cholesterol changes SCAP interactions and availability of its MELADL sorting signal to COPII machinery. The complex moves to the Golgi, where S1P cleaves the luminal SREBP loop and S2P performs intramembrane proteolysis. The released N-terminal transcriptional fragment enters the nucleus.

It activates uptake and synthesis programs, including LDLR and HMGCR. Increased LDL-receptor clearance can lower LDL-C, while compensatory synthesis partially offsets the response. Radhakrishnan et al. (2008) demonstrated switch-like SREBP-2 transport around 5 mol% ER cholesterol in a cellular model. This is an experimental sensor threshold, not a clinical assay or proof that 2 g phytosterols lowers every person's hepatic cholesterol below it. Specific percentages for increased LDLR or synthesis cannot be assigned to all consumers.

[![Reduced cholesterol delivery, SCAP/SREBP-2 transport from ER through COPII to Golgi, S1P/S2P cleavage and nuclear induction of LDLR and HMGCR.](https://api.nutrifit.health/api/v2/public/knowledge/files/images/nutrifit-scientific-20261002-phytosterols-phytostanols-npc1l1-cholesterol-absorption-feedback-en-v1.png)](https://api.nutrifit.health/api/v2/public/knowledge/files/images/nutrifit-scientific-20261002-phytosterols-phytostanols-npc1l1-cholesterol-absorption-feedback-en-v1.png)

Statins inhibit HMG-CoA reductase, ezetimibe targets NPC1L1, and plant sterols alter cholesterol availability in intestinal contents. Different intervention points explain potential additional LDL lowering, while true “synergy” requires an interaction analysis. Other LDL-receptor and PCSK9 mechanisms are covered in the article on [berberine and dihydroberberine](/knowledge/berberine-vs-dihydroberberine-ampk-pcsk9).

## 8. Clinical effects, dose response and combinations

Ras et al. (2014) pooled 124 studies with 201 strata. Across 0.6–3.3 g/day, mean LDL-C lowering rose gradually from approximately 6% to 12%, with benefit increasing to around 3 g/day. Studies above 4 g/day were too few and scattered for a reliable separate pooled estimate. Demonty et al. (2009) also modeled a continuous dose response. The findings support moderate LDL lowering at gram intakes, without a sharp plateau exactly at 2–2.5 g.

A saturating function can serve as an empirical model:

$$
E(D)=\frac{E_{\max}D}{ED_{50}+D}
$$

$D$ is free sterol/stanol-equivalent intake in g/day, $E(D)$ LDL-C lowering in percent, $E_{\max}$ the fitted maximal effect and $ED_{50}$ the dose producing half that effect. This Emax form does not establish Michaelis–Menten enzymatic kinetics inside micelles. Without fitted parameters it cannot calculate an individual's dose. Absolute concentration changes require baseline LDL-C: a 10% decrease from 3.0 mmol/L is 0.30 mmol/L, versus 0.50 mmol/L from 5.0 mmol/L.

Sterols and stanols produce comparable average LDL effects at commonly studied intakes. Lower stanol absorption does not establish zero risk. Non-HDL-C and ApoB can change alongside LDL, while triglyceride responses depend on baseline status; universal percentages for every lipoprotein are unjustified.

Adding sterols to statin treatment can further reduce LDL-C, but equating the result with “three statin dose doublings without toxicity” is incorrect. Drugs differ in potency, dose response and outcome evidence. At high cardiovascular risk, a food product does not replace treatments with established clinical benefit.

In Lin et al. (2011), 21 participants completed three three-week periods: control, ezetimibe 10 mg/day, and ezetimibe with phytosterols 2.5 g/day. Mean LDL-C was 129, 108 and 101 mg/dL respectively, and combination treatment enhanced changes in cholesterol balance. This small short trial did not include a statin in the compared regimen or cardiovascular events. It does not establish a universal 4–7% addition to every triple regimen. IMPROVE-IT (Cannon et al., 2015) tested ezetimibe plus statin after acute coronary syndrome; those outcome data cannot be transferred to phytosterol supplementation.

## 9. Product form, hydrolysis and nutrient balance

Esterifying the hydroxyl facilitates incorporation into a food-fat matrix. Ester mass includes the fatty acid: 2 g of esters and 2 g of free sterol equivalents are different amounts. Carboxyl ester lipase participates in digestive ester hydrolysis. The conceptual reaction is:

$$
\mathrm{Sterol{-}O{-}CO{-}R}+H_2O\rightarrow\mathrm{Sterol{-}OH}+\mathrm{R{-}COOH}
$$

$R$ denotes the fatty acid hydrocarbon group. Dispersion, matrix composition and hydrolysis affect free-sterol availability in the lumen. Properly formulated free sterols also work: Richelle et al. (2004) compared both forms in a beverage in 26 men and found similar cholesterol-absorption reduction. Poor water solubility alone does not make every free-sterol preparation ineffective.

The same short crossover study found lower β-carotene and α-tocopherol bioavailability. This was absorption in a particular experiment, rather than an automatic vitamin-deficiency diagnosis. Plasma tocopherol interpretation should account for changes in lipoprotein carriers. Carotenoids respond differently; “vitamins A, D and K never change” is too categorical. Varied vegetables and fruit support carotenoid intake, but a single portion cannot guarantee complete prevention of changes in everyone.

Taking a product with food helps its integration into digestive aggregates. Dietary fat stimulates cholecystokinin, bile release and pancreatic secretion, but this does not imply a universal minimum of 10–15 g fat or an absence of bile when fasting. The tested formulation and product directions matter; increasing dietary fat solely for a supplement is unnecessary.

## 10. Use and remaining uncertainties

| Situation | Meaning of the evidence |
| --- | --- |
| An adult with elevated LDL-C | An enriched food may provide moderate additional lowering within a diet; overall risk informs the decision |
| Statin or ezetimibe already prescribed | Additional lipid effects are possible; goals and combinations should be discussed with the treating clinician |
| Suspected familial hypercholesterolemia in a child | Specialist diagnosis is needed; a food product neither replaces therapy nor defines one pediatric regimen |
| Sitosterolemia | Avoid sterol/stanol-enriched foods and treat the transport disorder |
| Pregnancy, breastfeeding or a young child | Evidence is insufficient for self-prescribing enriched products; ordinary plant foods are distinct from supplements |

Response can be assessed by repeating the lipid profile after several weeks of a stable regimen, accounting for changes in diet, medication and adherence. Nonresponse does not establish an NPC1L1 defect; elevated plasma plant sterols are also not a simple stand-alone test for excessive absorption without clinical context.

The principal evidence limitation is the predominance of short lipid studies. The evidence considered here does not include a reliable trial establishing fewer infarctions or deaths specifically from phytosterol-enriched foods. Genetic disease, observational associations of circulating sterols and animal experiments inform mechanisms and potential risks, but cannot replace such a trial. The scientifically supported position combines established LDL lowering, a multicomponent intestinal barrier and uncertainty about long-term outcomes.

## FAQ

### Do phytosterols prevent myocardial infarction?

LDL-C lowering is established. Ezetimibe/statin outcome trials do not establish the same benefit for enriched foods; direct cardiovascular event reduction remains unconfirmed.

### Are stanols completely unabsorbed?

Absorption is much lower than cholesterol and many sterols, but low absorption does not mean absolute zero or proven zero risk.

### Are all free sterols ineffective?

No. Dispersion and food matrix matter; a randomized beverage study found similar cholesterol-absorption reductions with free and esterified sterols.

### Should intake exceed 3 g/day?

There is no universal individual dose. Average benefit increases to around 3 g/day; higher intakes are less well studied and do not justify self-directed escalation.

### Who should avoid enriched products?

Avoid them in confirmed sitosterolemia. Evidence is insufficient for self-prescribing during pregnancy, breastfeeding or early childhood.

## Sources

- [Ras RT, Geleijnse JM, Trautwein EA. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br J Nutr. 2014;112:214–219.](https://pubmed.ncbi.nlm.nih.gov/24780090/)
- [Demonty I et al. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr. 2009;139:271–284.](https://pubmed.ncbi.nlm.nih.gov/19091798/)
- [Huang CS, Yu X, Min X, Wang Z. Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition. Sci Adv. 2020;6:eabb1989.](https://pubmed.ncbi.nlm.nih.gov/32596471/)
- [Lee JY et al. Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature. 2016;533:561–564.](https://pubmed.ncbi.nlm.nih.gov/27144356/)
- [Altmann SW et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004;303:1201–1204.](https://pubmed.ncbi.nlm.nih.gov/14976318/)
- [Davis HR Jr et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem. 2004;279:33586–33592.](https://pubmed.ncbi.nlm.nih.gov/15173162/)
- [Berge KE et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000;290:1771–1775.](https://pubmed.ncbi.nlm.nih.gov/11099417/)
- [Armstrong MJ, Carey MC. Thermodynamic and molecular determinants of sterol solubilities in bile salt micelles. J Lipid Res. 1987;28:1144–1155.](https://pubmed.ncbi.nlm.nih.gov/3681139/)
- [Ge L et al. The cholesterol absorption inhibitor ezetimibe acts by preventing the endocytosis of NPC1L1. Cell Metab. 2008;7:508–519.](https://pubmed.ncbi.nlm.nih.gov/18522832/)
- [Li PS et al. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nat Med. 2014;20:80–86.](https://pubmed.ncbi.nlm.nih.gov/24336247/)
- [Temel RE et al. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest. 2007;117:1968–1978.](https://pubmed.ncbi.nlm.nih.gov/17571164/)
- [Miettinen TA et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med. 1995;333:1308–1312.](https://pubmed.ncbi.nlm.nih.gov/7566021/)
- [Lu K et al. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet. 2001;69:278–290.](https://pubmed.ncbi.nlm.nih.gov/11452359/)
- [Repa JJ et al. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem. 2002;277:18793–18800.](https://pubmed.ncbi.nlm.nih.gov/11901146/)
- [Yu L et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest. 2002;110:671–680.](https://www.jci.org/articles/view/16001)
- [Salen G, Ahrens EH Jr, Grundy SM. Metabolism of beta-sitosterol in man. J Clin Invest. 1970;49:952–967.](https://www.jci.org/articles/view/106315)
- [Salen G et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation. 2004;109:966–971.](https://pubmed.ncbi.nlm.nih.gov/14769702/)
- [Radhakrishnan A et al. Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Cell Metab. 2008;8:512–521.](https://pubmed.ncbi.nlm.nih.gov/19041766/)
- [Cannon CP et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–2397.](https://pubmed.ncbi.nlm.nih.gov/26039521/)
- [Mel’nikov SM, Seijen ten Hoorn JW, Eijkelenboom AP. Effect of phytosterols and phytostanols on the solubilization of cholesterol by dietary mixed micelles: an in vitro study. Chem Phys Lipids. 2004;127:121–141.](https://pubmed.ncbi.nlm.nih.gov/14725996/)
- [Racette SB et al. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study. Am J Clin Nutr. 2010;91:32–38.](https://pubmed.ncbi.nlm.nih.gov/19889819/)
- [Richelle M et al. Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans. Am J Clin Nutr. 2004;80:171–177.](https://pubmed.ncbi.nlm.nih.gov/15213045/)
- [Lin X et al. Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans. Circulation. 2011;124:596–601.](https://pubmed.ncbi.nlm.nih.gov/21768544/)
- [Noakes M et al. An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations. Am J Clin Nutr. 2002;75:79–86.](https://pubmed.ncbi.nlm.nih.gov/11756063/)
- [Vuorio AF et al. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH–North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500–506.](https://pubmed.ncbi.nlm.nih.gov/10669649/)
- [Diener AC et al. STEROL METHYLTRANSFERASE 1 controls the level of cholesterol in plants. Plant Cell. 2000;12:853–870.](https://pmc.ncbi.nlm.nih.gov/articles/PMC149089/)
- [Bouvier-Navé P, Husselstein T, Benveniste P. Two families of sterol methyltransferases are involved in the first and the second methylation steps of plant sterol biosynthesis. Eur J Biochem. 1998;256:88–96.](https://pubmed.ncbi.nlm.nih.gov/9746350/)
- [RCSB PDB 3QNT. Crystal structure of the N-terminal domain of human NPC1L1.](https://www.rcsb.org/structure/3QNT)
- [RCSB PDB 6V3F. Cryo-EM structure of rat NPC1L1 in apo state.](https://www.rcsb.org/structure/6V3F)
- [RCSB PDB 6V3H. Rat NPC1L1 with ezetimibe-PS analogue.](https://www.rcsb.org/structure/6V3H)
- [RCSB PDB 5DO7. Human ABCG5/ABCG8 heterodimer.](https://www.rcsb.org/structure/5DO7)
- [PubChem. Cholesterol: molecular formula, stereochemical structure and molecular weight.](https://pubchem.ncbi.nlm.nih.gov/compound/Cholesterol)
- [PubChem. Campesterol: molecular formula, stereochemical structure and molecular weight.](https://pubchem.ncbi.nlm.nih.gov/compound/Campesterol)
- [PubChem. beta-Sitosterol: molecular formula, stereochemical structure and molecular weight.](https://pubchem.ncbi.nlm.nih.gov/compound/beta-Sitosterol)
- [PubChem. Stigmasterol: molecular formula, stereochemical structure and molecular weight.](https://pubchem.ncbi.nlm.nih.gov/compound/Stigmasterol)
- [PubChem. Brassicasterol: molecular formula, stereochemical structure and molecular weight.](https://pubchem.ncbi.nlm.nih.gov/compound/Brassicasterol)
- [PubChem. Campestanol: molecular formula, stereochemical structure and molecular weight.](https://pubchem.ncbi.nlm.nih.gov/compound/Campestanol)
- [PubChem. Sitostanol: molecular formula, stereochemical structure and molecular weight.](https://pubchem.ncbi.nlm.nih.gov/compound/Sitostanol)
- [Association of rs2072183 SNP and serum lipid levels in the Mulao and Han populations. Primary genetic association study; NPC1L1 locus and gene organization.](https://pmc.ncbi.nlm.nih.gov/articles/PMC3422998/)