Phytosterol

β-sitosterol, a prototypical phytosterol

Phytosterols are phytosteroids, similar to cholesterol, that

serve as structural components of biological membranes
of plants.[1] They encompass plant sterols and stanols.[1] More
than 250 sterols and related compounds have been
identified.[2] Free phytosterols extracted from oils are
insoluble in water, relatively insoluble in oil, and soluble in alcohols.
Phytosterol-enriched foods and dietary supplements have been marketed for decades.[3] Despite
well-documented LDL cholesterol-lowering effects from long-term consumption of phytosterols,
there is insufficient evidence for an effect on cardiovascular diseases, fasting blood sugar, glycated
hemoglobin, or overall mortality rate.[4][5]

Structure
Nomenclature of the structure of a tetracyclic damarane triterpene

They have a fused polycyclic structure and vary in carbon side

chains and / or presence or absence of a double
bond (saturation).[3] They[clarification needed] are divided into 4,4-
dimethyl phytosterols, 4-monomethyl phytosterols, and 4-
desmethyl phytosterols based on the location of methyl groups
at the carbon-4 position.[6] Stanols are saturated sterols,
having no double bonds in the sterol ring structure.
The molecule in the article lead is β-sitosterol. The nomenclature is shown on the right.

• By removing carbon 242, campesterol is obtained.

• By removing carbons 241 and 242, cholesterol is obtained.
• Removing a hydrogen from carbons 22 and 23 yields stigmasterol (stigmasta-5,22-dien-3β-
ol).
• By hydrogenating the double bond between carbons 5 and 6, β-sitostanol (Stigmastanol) is
obtained.
• By hydrogenating the double bond between carbons 5 and 6 and removing carbon
242, campestanol is obtained.
• Removing carbon 242 and hydrogens from carbons 22 and 23, and inverting the
stereochemistry at C-24 yields brassicasterol (ergosta-5,22-dien-3β-ol).
• Further removal of hydrogens from carbons 7 and 8 from brassicasterol
yields ergosterol (ergosta-5,7,22-trien-3β-ol). Important: Ergosterol is not a plant sterol.
Ergosterol is a component of fungal cell membranes, serving the same function in fungi that
cholesterol serves in animal cells.
In addition:

• Esterification of the hydroxyl group at carbon 3 with fatty/organic acids or carbohydrates

results in plant sterol esters, i.e. oleates, ferulates and (acyl) glycosides.

Cholesterol

Dietary phytosterols
 The richest naturally occurring sources of phytosterols are vegetable oils and products made from
them. Sterols can be present in the free form and as fatty acid esters and glycolipids. The bound
form is usually hydrolyzed in the small intestines by pancreatic enzymes.[7] Some of the sterols are
removed during the deodorization step of refining oils and fats, without, however, changing their
relative composition. Sterols are therefore a useful tool in checking authenticity.
As common sources of phytosterols, vegetable oils have been developed as margarine products
highlighting phytosterol content.[3] Cereal products, vegetables, fruit and berries, which are not as
rich in phytosterols, may also be significant sources of phytosterols due to their higher intakes.[8]
The intake of naturally occurring phytosterols ranges between ~200–300 mg/day depending on
eating habits.[9] Specially designed vegetarian experimental diets have been produced yielding
upwards of 700 mg/day.[10] The most commonly occurring phytosterols in the human diet are β-
sitosterol, campesterol and stigmasterol,[3] which account for about 65%, 30% and 3% of diet
contents, respectively.[11] The most common plant stanols in the human diet are sitostanol and
campestanol, which combined make up about 5% of dietary phytosterol.[12]
Sterol composition in crude oils (as percentage of total sterol fraction)

β- ∆5- ∆7- ∆7-

Cholester Brassicaster Campester Stigmaster
Sitoster Avenaster Avenaster Stigmaster
ol ol ol ol
ol ol ol ol

Coconut
0.6 – 2 0 – 0.9 7 – 10 12 – 18 50 – 70 5 – 16 0.6 – 2 2–8
oil
Corn oil 0.2 – 0.6 0 – 0.2 18 – 24 4–8 55 – 67 4–8 1–3 1–4
Cottonse
0.7 – 2.3 0.1 – 0.9 7.2 – 8.4 1.2 – 1.8 80 – 90 1.9 – 3.8 1.4 – 3.3 0.7 – 1.4
ed oil
75.6 –
Olive oil 0 – 0.5 2.3 – 3.6 0.6 – 2 3.1 – 14 0–4
90
50.2 –
Palm oil 2.2 – 6.7 18.7 – 29.1 8.9 – 13.9 0 – 2.8 0 – 5.1 0.2 – 2.4
62.1
Palm 62.6 –
1 – 3.7 0 – 0.3 8.4 – 12.7 12.3 – 16.1 4–9 0 – 1.4 0 – 2.1
kernel oil 70.4
Peanut
0.6 – 3.8 0 – 0.2 12 – 20 5 – 13 48 – 65 7–9 0–5 0–5
oil
Rapeseed
0.4 – 2 5 – 13 18 – 39 0 – 0.7 45 – 58 0 – 6.6 0 – 0.8 0–5
oil
Soybean
0.6 – 1.4 0 – 0.3 16 – 24 16 – 19 52 – 58 2–4 1 – 4.5 1.5 – 5
oil
Sunflowe
0.2 – 1.3 0 – 0.2 7 – 13 8 – 11 56 – 63 2–7 7 – 13 3–6
r oil

Health claims
EFSA
The European Foods Safety Authority (EFSA) concluded that blood cholesterol can be reduced on
average by 7 to 10.5% if a person consumes 1.5 to 2.4 grams of plant sterols and stanols per day,
an effect usually established within 2–3 weeks. Longer-term studies extending up to 85 weeks
showed that the cholesterol-lowering effect could be sustained.[14] Based on this and other efficacy
data, the EFSA scientific panel provided the following health advisory: "Plant sterols have been
shown to lower/reduce blood cholesterol. Blood cholesterol lowering may reduce the risk
of coronary heart disease".[15]
FDA[edit]
The FDA has approved the following claim for phytosterols: For plant sterol esters: (i) Foods
containing at least 0.65 g per serving of plant sterol esters, eaten twice a day with meals for a daily
total intake of at least 1.3 g, as part of a diet low in saturated fat and cholesterol, may reduce the
risk of heart disease. A serving of [name of the food] supplies ___grams of vegetable oil sterol
esters.[16] For plant stanol esters: (i) Foods containing at least 1.7 g per serving of plant stanol
esters, eaten twice a day with meals for a total daily intake of at least 3.4 g, as part of a diet low in
saturated fat and cholesterol, may reduce the risk of heart disease. A serving of [name of the food]
supplies ___grams of plant stanol esters.[17] Reviewing clinical trials involving phytosterol
supplementation, the FDA concluded that when consumed in the range of 1 to 3 grams in enriched
foods, phytosterols resulted in statistically significant (5-15%) reductions in blood LDL
cholesterol levels relative to placebo. The FDA also concluded that a daily dietary intake of 2
grams a day of phytosterols (expressed as non-esterified phytosterols) is required to demonstrate
a relationship between phytosterol consumption and cholesterol lowering for reduced CVD risk.[18]
Health Canada[edit]
Health Canada reviewed the evidence of 84 randomized controlled trials published between 1994
and 2007 involving phytosterol supplementation. An average 8.8% reduction in LDL-cholesterol
was observed at a mean intake of 2 grams per day.[19] Health Canada concluded that sufficient
scientific evidence exists to support a relationship between phytosterol consumption and blood
cholesterol lowering. Based on this evidence, Health Canada approved the following statements
for qualifying foods intended for hypercholesterolemic individuals: Primary statement: "[serving
size from Nutrition Facts table in metric and common household measures] of [naming the
product] provides X% of the daily amount* of plant sterols shown to help reduce/lower cholesterol
in adults." Two additional statements that could be used in combination or alone, adjacent to the
primary statement, without any intervening printed, written or graphic material: "Plant sterols help
reduce [or help lower] cholesterol." This statement when used, shall be shown in letters up to twice
the size and prominence as those of the primary statement. "High cholesterol is a risk factor for
heart disease." This statement when used, shall be shown in letters up to the same size and
prominence as those of the primary statement.

Cholesterol lowering[edit]
The ability of phytosterols to reduce cholesterol levels was first demonstrated in humans in
1953.[20][21] From 1954 to 1982, phytosterols were subsequently marketed as a pharmaceutical
under the name Cytellin as a treatment for elevated cholesterol.[22]
Unlike the statins, where cholesterol lowering has been proven to reduce risk of cardiovascular
diseases (CVD) and overall mortality under well-defined circumstances, the evidence has been
inconsistent for phytosterol-enriched foods or supplements to lower risk of CVD, with two reviews
indicating no or marginal effect,[23][4] and another review showing evidence for use of dietary
phytosterols to attain a cholesterol-lowering effect.[24]
Coadministration of statins with phytosterol-enriched foods increases the cholesterol-lowering
effect of phytosterols, again without any proof of clinical benefit and with anecdotal evidence of
potential adverse effects.[23] Statins work by reducing cholesterol synthesis via inhibition of the
rate-limiting HMG-CoA reductase enzyme. Phytosterols reduce cholesterol levels by competing
with cholesterol absorption in the gut via one or several possible mechanisms,[25][26][27] an effect
that complements statins. Phytosterols further reduce cholesterol levels by about 9% to 17% in
statin users.[28] The type or dose of statin does not appear to affect the cholesterol-lowering efficacy
of phytosterols.[29]
Because of their cholesterol reducing properties, some manufacturers are using sterols or stanols
as a food additive.[3][30]

Safety[edit]
Phytosterols have a long history of safe use,[3] dating back to Cytellin, the pharmaceutical
preparation of phytosterols marketed in the US from 1954 to 1982.[22] Phytosterol esters
have generally recognized as safe (GRAS) status in the US.[31] Phytosterol-containing functional
foods were subject to postlaunch monitoring after being introduced to the EU market in 2000, and
no unpredicted side effects were reported.[32]
A potential safety concern regarding phytosterol consumption is in patients with phytosterolaemia,
a rare genetic disorder which results in a 50- to 100-fold increase in blood plant sterol levels and
is associated with rapid development of coronary atherosclerosis. Phytosterolaemia has been
linked to mutations in the ABCG5/G8 proteins which pump plant sterols out of enterocytes and
hepatocytes into the lumen and bile ducts, respectively. Plant sterol levels in the blood have been
shown to be positively, negatively or not associated with CVD risk, depending on the study
population investigated.[33][34][35][36][37][38][39][40]
The link between plant sterols and CVD or CHD risk is complicated because phytosterol levels
reflect cholesterol absorption. (See Phytosterols as a marker for cholesterol absorption).[citation
needed]

Sterol vs stanol[edit]
The equivalent ability and safety of plant sterols and plant stanols to lower cholesterol continues
to be a hotly debated topic. Plant sterols and stanols, when compared head-to-head in clinical trials,
have been shown to equally reduce cholesterol levels.[41][42][43] A meta-analysis of 14 randomized,
controlled trials comparing plant sterols to plant stanols directly at doses of 0.6 to 2.5 g/day showed
no difference between the two forms on total cholesterol, LDL cholesterol, HDL cholesterol, or
triglyceride levels.[44] Trials looking at high doses (> 4 g/day) of plant sterols or stanols are very
limited, and none have yet to be completed comparing the same high dose of plant sterol to plant
stanol.
The debate regarding sterol vs. stanol safety is centered on their differing intestinal absorption and
resulting plasma concentrations. Phytostanols have a lower estimated intestinal absorption rate
(0.02 - 0.3%) than phytosterols (0.4 - 5%) and consequently blood phytostanol concentration is
generally lower than phytosterol concentration.[23]

Research
Phytosterols are under preliminary research for their potential to inhibit lung, stomach, ovarian
and breast cancers,[45][46] as well as colon and prostate cancers.[47]

Functions in plants
Sterols are essential for all eukaryotes. In contrast to animal and fungal cells, which contain only
one major sterol, plant cells synthesize an array of sterol mixtures in
which sitosterol and stigmasterol predominate.[48] Sitosterol regulates membrane fluidity and
permeability in a similar manner to cholesterol in mammalian cell membranes.[49] Plant sterols can
also modulate the activity of membrane-bound enzymes.[49] Phytosterols are also linked to plant
adaptation to temperature and plant immunity against pathogens.[50]