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Phytosterols as functional food ingredients: Linkages to cardiovascular disease and cancer

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  • Nutritional Fundamentals for Health Inc

Abstract

To examine experimental evidence that has examined association of phytosterols and the reduction of the risk of cardiovascular disease and cancer. Phytosterols exist as naturally occurring plant sterols that are present in the nonsaponifiable fraction of plant oils. Phytosterols are plant components that have a chemical structure similar to cholesterol except for the addition of an extra methyl or ethyl group; however, phytosterol absorption in humans is considerably less than that of cholesterol. In fact, phytosterols reduce cholesterol absorption, although the exact mechanism is not known, and thus reduce circulating levels of cholesterol. The efficacy of phytosterols as cholesterol-lowering agents have been shown when incorporated into fat spreads as well as other food matrices. In addition, phytosterols have been combined with other beneficial dietary components including fish and olive oils, psyllium and beta-glucan to enhance their effect on risk factors of cardiovascular disease. Phytosterols appear not only to play an important role in the regulation of cardiovascular disease but also to exhibit anticancer properties. A side effect associated with the consumption of phytosterols is that they reduce the blood levels of carotenoid. Nevertheless, it has been suggested that compensation for this impact on serum carotenoid levels can occur either by increasing the intake of carotenoid-rich foods or by taking supplements containing these carotenoids. Dietary phytosterols appear to play an important role in the regulation of serum cholesterol and to exhibit anticancer properties.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Phytosterols as functional food ingredients: linkages to
cardiovascular disease and cancer
Peter J.H. Jones
a
and Suhad S. AbuMweis
b
Introduction
Phytosterols exist as naturally occurring plant sterols that
are present in the nonsaponifiable fraction of plant oils.
Structurally, phytosterols are similar to cholesterol
except for substitutions on the sterol side chain at the
C24 position. Phytosterols are not synthesized in
humans, are poorly absorbed, and are excreted faster
from the liver than cholesterol, which explains their low
abundance in human tissues. The primary phytosterols
in the diet are sitosterol, stigmasterol, and campesterol.
Typical consumption of plant sterols is approximately
200 –400 mg/day. The most abundant phytosterol in
western diets is beta-sitosterol, but these materials are
found in the tissues and plasma of healthy individuals
at concentrations 8001000 times lower than that of
endogenous cholesterol.
Epidemiological evidence indicates a reduced incidence
of various types of cancer, cardiovascular disease, and
other chronic conditions in populations consuming
diets rich in vegetables and fruits. Although many
studies have concentrated on the protective effects of
minerals, trace elements and vitamins, it is only in recent
years that the phytosterol content of the foods has been
taken into account and yielded positive correlations in
terms of chronic disease risk reduction. The purpose
of this review is to examine experimental evidence of
such associations.
Reduction of serum cholesterol levels
Phytosterols have been shown to inhibit the uptake of both
dietary and endogenously produced (biliary) cholesterol
from intestinal cells. Such inhibition results ina decrease in
serum total and LDL-cholesterol (LDL-C) levels [1
].
Levels of HDL-cholesterol and triglycerides do not appear
to be affected by dietary phytosterol consumption.
Human studies
For example, a 30-day trial [2] has shown that a 1.7 g/day
dose of oil phytosterols containing 20% sitostanol and
a
Richardson Centre for Functional Foods and
Nutraceuticals, University of Manitoba, Smartpark,
Winnipeg, Manitoba, Canada and
b
Department of
Clinical Nutrition and Dietetics, Faculty of Allied Health
Sciences, The Hashemite University, Zarqa, Jordan
Correspondence to Peter J.H. Jones, PhD, Richardson
Centre for Functional Foods and Nutraceuticals,
University of Manitoba, Smartpark, 196 Innovation
Drive, Winnipeg, MB, Canada R3T 6C5
Tel: +1 204 474 8883; fax: +1 204 474 7552;
e-mail: peter_jones@umanitoba.ca
Current Opinion in Clinical Nutrition and
Metabolic Care 2009, 12:147– 151
Purpose of review
To examine experimental evidence that has examined association of phytosterols and
the reduction of the risk of cardiovascular disease and cancer.
Recent findings
Phytosterols exist as naturally occurring plant sterols that are present in the
nonsaponifiable fraction of plant oils. Phytosterols are plant components that have a
chemical structure similar to cholesterol except for the addition of an extra methyl or
ethyl group; however, phytosterol absorption in humans is considerably less than that of
cholesterol. In fact, phytosterols reduce cholesterol absorption, although the exact
mechanism is not known, and thus reduce circulating levels of cholesterol. The efficacy
of phytosterols as cholesterol-lowering agents have been shown when incorporated
into fat spreads as well as other food matrices. In addition, phytosterols have been
combined with other beneficial dietary components including fish and olive oils, psyllium
and beta-glucan to enhance their effect on risk factors of cardiovascular disease.
Phytosterols appear not only to play an important role in the regulation of cardiovascular
disease but also to exhibit anticancer properties. A side effect associated with the
consumption of phytosterols is that they reduce the blood levels of carotenoid.
Nevertheless, it has been suggested that compensation for this impact on serum
carotenoid levels can occur either by increasing the intake of carotenoid-rich foods or by
taking supplements containing these carotenoids.
Summary
Dietary phytosterols appear to play an important role in the regulation of serum
cholesterol and to exhibit anticancer properties.
Keywords
cancer, cholesterol, phytosterols
Curr Opin Clin Nutr Metab Care 12:147– 151
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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
80% other phytosterols (primarily sitosterol and campes-
terol) reduced LDL-C by 24.4% in hypercholesterolemic
men compared with 8.9% with the control diet.
Moreover, a 9-week double-blind, crossover study was
designed to assess the cholesterol-lowering effect of two
table spreads fortified with free (nonesterified) vegetable
oil sterols (mainly from soybean oil) or with sheanut oil
sterols [3]. Plasma total cholesterol and LDL-C concen-
trations were statistically significantly reduced by 3.8 and
6%, respectively, for the spread enriched with free soy-
bean oil sterols compared with the control spread.
Other studies have determined the effect of whole corn
oil and purified phytosterol-free corn oil triglyceride on
cholesterol absorption in single-meal tests [4]. Deuter-
ated cholesterol was included in the meal and the plasma
enrichment was measured several days later. Cholesterol
tracer in plasma following a test meal containing sterol-
free oil was 38% (10%) higher than that observed using
native corn oil. Phytosterols were the principal nontrigly-
ceride component of commercial corn oil and readdition
of corn oil sterols to sterol-free oil restored cholesterol
absorption to the original value. Amounts of corn oil
sterols as small as 150 mg reduced cholesterol absorption
significantly. These data show a prominent effect of corn
oil phytosterols on cholesterol absorption at doses much
lower than those used in commercial supplements.
More recently, a clinical study [5] involving 15 hyper-
cholesterolemic persons showed that 1.8 g/day of free
sterols, free stanols, or a free stanol/sterol mixture incor-
porated into a dairy fat spread gave statistically similar
reductions in LDL-C in the range of 10–15%.
Factors affecting efficacy of phytosterols
The physical state of plant sterols may have an impact on
their cholesterol-lowering effect. For example, in a
double-blind randomized, placebo-controlled study, a
crystallizing method was used to add plant sterols into
dietary fats and oils homogeneously [6]. Hypercholester-
olemic participants consuming 1.5 or 3.0 g/day of free
unesterified plant sterols in this ‘microcrystalline’ form
experienced a 7.511.6% reduction in LDL-C levels.
However, conflicting data raise some doubts about the
biologic activity of the microcrystalline phytosterols.
During single-meal tests in humans, crystalline phytos-
terols (1000 mg) did not reduce absorption of labeled
cholesterol consistently, whereas 300 mg of phytosterols
complexed with lecithin reduced cholesterol absorption
by 34% [7]. Despite the increased sterol purity, it has
been suggested that the extremely stable state of the
crystalline structure requires both energy and time to
disrupt. Crystalline phytosterols took several days to
reach an equilibrium state during solubilization in
solutions of bile salts [8]. There is almost no transfer
of crystalline phytosterols from the solid state to the
micelles of artificial bile solutions over periods of a few
hours at physiologic temperature [7]. These in-vitro
findings suggest that it is unlikely that phytosterol crys-
tals are biologically active.
Phytosterols have been added to food matrices other than
fat spread including low-fat milk [9], bakery products
[10], orange juice [11], cereal bars [12], low-fat and nonfat
beverages [13], and chocolate bars [14]. A recent analysis
[1
] of these trials showed that compared with control,
LDL levels were reduced by 0.33 mmol/l [95% confi-
dence interval (CI) 0.38 to 0.28], 0.32 mmol/l (95% CI
0.40 to 0.25), 0.34 mmol/l (95% CI 0.40 to 0.28),
and 0.20 mmol/l (95% CI 0.28 to 0.11) in the fat spreads,
mayonnaise and salad dressing, milk and yoghurt drinks,
and other food products, respectively. Other food products
subgroup included studies testing the efficacy of plant
sterols incorporated in chocolate and cereal bars, bev-
erages, juices, meat and croissants, and muffins. Therefore,
the matrix to which phytosterols are added can influence
their efficacy as cholesterol-lowering agents.
It is also relevant to compare the cholesterol-lowering
activity of vegetable oil-based table spreads enriched in
plant sterol esters for normocholesterolemic with mildly
hypercholesterolemic participants. This was done in
two studies [15,16] in which consumption of margarine
or spreads enriched with plant sterols effectively lowered
plasma total and LDL-C concentrations. However,
the effects on blood lipids did not differ between nor-
mocholesterolemic and mildly hypercholesterolemic
participants.
These effects can also be seen even for those individuals
who are already on a low-cholesterol diet. For example, a
study chose to work with people following a National
Cholesterol Education Program Step I diet. Participants
consuming 1.1 and 2.2g of sterols per day had total
cholesterol values that were 5.2 and 6.6% lower, LDL-C
values that were 7.6 and 8.1% lower, respectively, than
values for the control group [17]. In another clinical trial, a
combination of low-fat margarine and milk enriched with
plant sterols reduced LDL-C by 7.7% and apolipoprotein
B by 4.6%, compared to placebo, in mildly hypercholes-
terolemic participants [18]. So plant sterols can offer an
additional, significant reduction in serum cholesterol
concentrations to that obtained with a low-fat diet alone.
Phytosterols in combination with other
agents
A recent set of studies compared the cholesterol-lowering
efficacy of different esters of plant sterols [19,20]. Partici-
pants were fed five different dietary sterols including
148 Lipid metabolism and therapy
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olive oil, fish oil, and fatty acid plant sterol esters of
sunflower oil, as well as olive oil, and fish oil at level of
1.7 g/day for 28 days, each separated by washout periods.
Diets were controlled precisely so that participants
ate meals provided from a central metabolic kitchen to
maintain weight balance. Plant sterol-fish oil ester
reduced fasting and postprandial plasma triacylglycerol
levels compared with plant sterol-sunflower oil ester by
39 and 40%, respectively. Compared with an olive oil
diet, plant sterol-fish oil ester and plant sterol-sunflower
oil ester lowered LDL-C levels by 3 and 6%, respect-
ively. HDL-cholesterol levels were not affected by any of
the treatments. Fish oil and sunflower oil plant sterols
resulted in a lower total cholesterol : HDL-cholesterol
ratio and lower apolipoprotein B levels than olive oil
and fish oil.
Phytosterols are also effective when combined with other
dietary factors including psyllium [21], fish oil [22

],
beta-glucan [23], or statin drugs [24,25] and could be
useful in secondary prevention of heart disease when
greater targeted reductions in LDL-C are needed.
Mechanism of action of phytosterols
The exact mechanism by which phytosterols decrease
serum cholesterol levels is not completely understood,
but several theories have been proposed [26]. One of
them suggests that cholesterol in the intestine, already
marginally soluble, is precipitated into a nonabsorbable
state in the presence of added phytosterols and stanols.
Another theory is based on the fact that cholesterol must
enter bile-salt and phospholipid-containing ‘mixed
micelles’ in order to pass through intestinal cells and to
be absorbed into the bloodstream. Moreover, phytosterols
may modulate the action of key transporters involved in
cholesterol absorption (Fig. 1). Cholesterol absorption is a
very important physiological mechanism that regulates
cholesterol metabolism. A recent trial showed that efficacy
of phytosterols is not influenced by dietary cholesterol
intake in hypercholesterolemic individuals [27]. Both
dietary cholesterol (300 mg/day) and recirculating biliary
cholesterol (1000 mg/day) mix in the intestine and are
partially absorbed. Failure to reabsorb intestinal choles-
terol is the principal means of cholesterol elimination from
the body. Some studies show that phytosterols compete
with and displace cholesterol from bile salt/phospholipid
micelles, the form from which cholesterol absorption
occurs. During one trial, nine adults were fed a meal
containing 500 mg of cholesterol and 1 g beta-sitosterol
or 2 g beta-sitosteryl oleate [28]. The addition of beta-
sitosterol resulted in a 42% decrease in cholesterol
absorption, and the beta-sitosteryl oleate caused a 33%
reduction compared to the control group, which resulted
in a consequent decrease in plasma cholesterol. Sitos-
terol has increased affinity for biliary micelles compared
with cholesterol, so sitosterol uptake by micelles is
energetically favored. Further evidence of the import-
ance of micellar solubility is the finding that the absorb-
ability of different sterols is directly related to their
equilibrium micellar concentration [8].
Unlike cholesterol, phytosterols, and to a greater extent,
phytostanols, are poorly absorbed and the small amount
that is absorbed is actively re-excreted in bile. This
results in low serum levels of these sterol molecules.
The inhibition of cholesterol absorption is thought to
produce a state of relative cholesterol deficiency that is
followed by upregulation of cholesterol biosynthesis and
LDL receptor activity [29]. Although the exact effect on
serum lipoprotein levels is not yet known, it is interesting
to notice that some of the known effects of vegetable fats
on lipid metabolism are compatible with known mech-
anisms of action for phytosterols. For example, some
unsaturated vegetable oils increase hepatic LDL recep-
tor activity, decrease LDL production, and increase LDL
clearance. These actions correspond to what is anticip-
ated from the known effect of phytosterols to reduce
delivery of dietary and biliary cholesterol to the liver.
Reduction of cancer risk
Several studies suggest a protective role of phytosterols,
especially beta-sitosterol, from colon, prostate, and breast
cancer. Animal studies have investigated the effect of
Phytosterols as functional food ingredients Jones and AbuMweis 149
Figure 1 Mechanism of action of phytosterols
Phytosterols may reduce cholesterol absorption by competing with
cholesterol for incorporation into the bile salts micelles, or for uptaking
of cholesterol by enterocytes through Niemann Pick C1 Like 1
(NPC1L1) transporter. In addition, phytosterols may enhance choles-
terol excretion back into the intestinal lumen through the adenosine
triphosphate binding cassette G 5 (ABCG5) and G 8 (ABCG8) trans-
porters. Phytosterols could also prevent esterification of the free cho-
lesterol into cholesterol esters and thus its assembling into the
chylomicrons. As a result of reducing cholesterol absorption by phytos-
terols, the cholesterol synthesis rate increase, but the net effect is a
reduction in LDL-cholesterol levels.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
dietary phytosterols on human breast cancer cell line
xenografted in mice [30]. After 8 weeks, the tumor size
in animals fed phytosterols was 33% smaller and they had
20% fewer metastases to lymph nodes and lungs than the
control group (cholesterol-fed). The tumor weight of the
animals fed the phytosterol diet was also less than that of
the cholesterol group. It is concluded that dietary phytos-
terols retard the growth and spread of breast cancer cells.
An in-vitro study [31] showed that tumor growth of
HT-29 cells (a human colon cancer cell line) was effec-
tively inhibited by beta-sitosterol as compared to cho-
lesterol or to the control (no sterol supplementation).
After supplementation with 16 mmol/l beta-sitosterol
for 9 days, cell growth was only one-third that of cells
supplemented with equimolar concentration of choles-
terol. Similar results to those obtained in HT-29 cells, but
at a lower extent, in LNCaP, a human prostate cancer cell
line [32]. Compared with cholesterol, beta-sitosterol
(16 mmol/l) decreased growth by 24% and induced apop-
tosis four-fold. More whole animal and clinical research
is required, however, before we can place too much
emphasis on the results of in-vitro work.
Dietary supplementation of beta-sitosterol at 60 mg/day
for 6 months has been shown to improve significantly the
clinical symptoms of prostatic hyperplasia in humans
[33]. This disorder, which is benign and does not lead
to prostate cancer, is common among older men and
results in restricted urinary flow and polyuria due to
the enlargement of the gland. In Europe, prostatic hyper-
plasia is treated clinically with beta-sitosterol-containing
products.
The exact mechanism by which phytosterols offer pro-
tection from cancer is not known. However, several
theories have been reviewed [34]: they are incorporated
in the cell membrane, altering membrane fluidity and the
activity of membrane-bound enzymes. They can alter
signal transduction in pathways leading to tumor growth
and stimulate apoptosis in tumor cell lines. They have
been shown to enhance in-vitro human peripheral blood
lymphocyte and T-cell proliferation in vitro, which
suggests a possible stimulation of the immune system
function. Finally, by altering the level of fecal sterols
resulting from the conversion of cholesterol and primary
bile acids to coprostanol and secondary bile acids by
bacterial action in the large intestine, plant sterols may
play a role in the prevention of colon cancer.
Effects on the absorption of fat soluble vitamins and
antioxidants
The most important concern about plant sterols is that
they reduce the absorption of some fat-soluble vitamins.
A review of some of these randomized trials showed that
plant sterols and stanols lower blood concentrations of
beta-carotene by about 25%, concentrations of alpha-
carotene by 10%, and concentrations of vitamin E by
8% [35]. However, an important point in the interpret-
ation of these results is that a key role for these vitamins
may be to protect LDL-C from oxidation. Sterols appear
to reduce the amount of LDL-C, and lipophilic caroten-
oids and tocopherols are known to be associated with
LDL particles. Thus, it may be appropriate to adjust, or
correct, blood concentrations of these vitamins for the
lower LDL-C concentrations. With this adjustment, sta-
nols and sterols did not significantly lower blood concen-
tration of vitamin E, but concentrations of beta-carotene
were reduced by 819%.
It has been suggested that compensation for this impact
on serum carotenoid levels can occur either by increasing
the intake of carotenoid-rich foods or by taking supple-
ments containing these carotenoids. This has been
attempted in one clinical study, which indicated that
an increase in dietary carotenoids when consuming plant
sterols or stanols was effective in maintaining plasma
carotenoid levels [36].
A recent study showed that consumption of phytosterol-
fish oil ester resulted in higher beta-carotene and retinol
levels than other phytosterol esters [37]. Finally, it has
been noted that administration of free phytosterols and
phytostanols may not induce malabsorption of fat-soluble
vitamins and antioxidants as much as that caused from
consumption of the fatty acid ester forms [38]. If this is
verified in more studies, it might bring even more atten-
tion to the use of the free phytosterols and phytostanols in
functional foods.
Conclusion
Dietary phytosterols appear to play an important role in
the regulation of serum cholesterol and appear to provo-
catively exhibit anticancer properties. These data pro-
vide a strong rationale for their use in functional foods.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
of special interest
 of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (pp. 211 212).
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Phytosterols as functional food ingredients Jones and AbuMweis 151
... On the other hand, a number of illness, such as diabetes, heart disease, and arthritis, can be brought on by persistent inflammation. Numerous in In-vivo investigation have shown that P. thonningii root has anti-inflammatory properties (Ighodaro et al.,2012;Jones & AbuMweis, 2009). ...
... These compounds can scavenge free radicals and inhibit microbial growth, supporting their use in oxidative stress management and infection treatment. Moreover, the slight presence of phytosterols and saponins in the extract aligns with their documented benefits in reducing cholesterol levels and boosting immunity, as reported by (Jones & AbuMweis, 2009;Zhang et al., 2024). The absence of flavonoids and steroids in the extract suggests limitations in certain antioxidant and hormonal activities, respectively, which are typically associated with these compounds (Chaves et al., 2016). ...
... Higher concentrations of the root crude extract show an increasing percentage inhibition of oxidation, indicating the existence of antioxidant chemicals in the roots of Piliostigma thonningii. This finding is consistent with research by (Jones & AbuMweis, 2009) who used comparable antioxidant tests to demonstrate strong antioxidant activity in Piliostigma thonningii root extracts. ...
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Medicinal plants have been widely explored for their therapeutic potential due to their rich phytochemical composition. Piliostigma thonningii, a widely used plant in traditional medicine, is known for its diverse bioactive compounds with potential health benefits. This study aims to the phytochemical composition, antioxidant activity, and anti-inflammatory properties of the methanol root extract of Piliostigma thonningii. Standard qualitative methods revealed the presence of anthraquinones, alkaloids, phenols, tannins, phytosterols, and saponins, while cardiac glycosides, glycosides, flavonoids, and steroids were absent. Antioxidant potential was assessed using DPPH radical-scavenging, ferric reducing antioxidant potential (FRAP), and hydrogen peroxide scavenging assays, revealing dose-dependent radical inhibition. The root crude extract of Piliostigma thonningii exhibits dose-dependent antioxidant activity across DPPH, FRAP, and hydrogen peroxide scavenging assays, with higher concentrations showing increased efficacy. The presence of bioactive phytochemicals, including flavonoids and phenolic compounds, contributes to its ability to reduce oxidative stress and inhibit free radicals. Anti-inflammatory activity was evaluated in vitro via albumin denaturation inhibition and in vivo using the carrageenan-induced paw edema model in rats. At 100 mg/kg, the extract exhibited moderate anti-inflammatory effects, with paw edema peaking at 4 hours (9.093 ± 0.071) and declining at 5 hours (7.362 ± 0.089). However, higher concentrations (200 and 400 mg/kg) showed increased inflammation, peaking at 4 hours (19.621 ± 0.033) and 5 hours (20.001 ± 0.056), respectively. Diclofenac (negative control) demonstrated controlled inflammatory responses, with edema peaking at 4 hours (10.585 ± 0.066) and declining by 5 hours (9.207 ± 0.022). These findings suggest that while the extract has notable anti-inflammatory effects at lower doses, higher doses may exhibit pro-inflammatory tendencies. This study highlights the potential of Piliostigma thonningii root extract as a natural source of anti-inflammatory agents, warranting further investigation for therapeutic applications.
... [91,92] The consumption of plant-based ingredients with a high content of antioxidant compounds and phytosterols play an important role in lowering total and LDL cholesterol and regulating cardiovascular diseases. [14,93] A diet enriched with quinoa protein-rich flour in male Wistar rats has been observed to positively affect the plasma lipid profile by reducing total cholesterol and LDL cholesterol levels. However, it was noted to increase the level of plasma inflammatory markers. ...
Article
Quinoa is a particularly nutrient-rich grain crop, which is abundant in micro-nutrients, fibre, and essential amino acids, making it an excellent staple food source. The current review provides an outline of the antioxidant and anti-inflammatory properties of quinoa and a critical evaluation of health benefits following its consumption focusing on diabetes and diabetes risk factors,non-alcoholic fatty liver disease, hypertension, cancer risk, body weight regulation and obesity, and cardiovascular disease risk factors. Quinoa has been demonstrated to have as hypoglycaemic effect and inducing favour-able changes in cholesterol, HDL and LDL levels, inflammatory markers as well as body weight in humans.
... Cancers of the breast, colon, prostate, and other organs may also be prevented by it. Because phytosterols physically bind to carcinogens, they have an anticarcinogenic effect (Jones & Abumweis, 2009). With an average phytosterol density of 1054 mg/kg-25% more than winter wheat-einkorn wheat, a type of Triticum, has the greatest phytosterol density. ...
... In addition to their lipidlowering effects, plant molecules have been shown to have other potential health benefits. For example, plant sterols are associated with a lower risk of certain cancers and may have anti-inflammatory properties (Jones and AbuMweis 2009). The role of plant products in the treatment of hyperlipidemia has been the subject of numerous studies in recent years. ...
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A known risk factor for cardiovascular disease is hyperlipidemia. Herbal therapy for hyperlipidemia is popular because it has fewer adverse effects, is less costly, and is readily available. Several medicinal herbs have been shown in studies to lower blood cholesterol levels by decreasing the action of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA). However, conducting direct studies in animals and humans to evaluate the efficacy of herbal medicines for hyperlipidemia raises ethical concerns. Therefore, in silico studies are needed to evaluate the safety and efficacy of phytoconstituents before animal studies and human clinical trials are conducted. This problem can be solved by using insilico studies. Molecular docking has become increasingly important as a method for drug discovery. Molecular docking can be used to mimic the interaction between a small molecule and a protein at the atomic level. This allows us to define the behaviour of small molecules at the binding sites of target proteins and shed light on important biochemical processes. Molecular docking plays an important role in the search for new drugs at significantly lower cost and faster pace. Aim: The aim of study is to evaluate natural products against hyperlipidemia using molecular docking. Material and Natural products were selected after reading various literature sources. For each chemical, a molecular structure file was obtained from the PubChem database. The crystal structure of the protein (PDB ID: 1HW9) was obtained from the Protein Data Bank. The protein molecule was freed from all bound components (ligands and cofactors) and solvent molecules. Active binding sites were identified using the Biovia Discovery programme. PyRx was used to perform docking experiments for natural products against the 1HW9 protein. Results of molecular docking study shows that indirubin has a more negative binding energy value than atorvastatin and it binds more strongly to the receptor HMG-CoA. In this study, numerous bioactive compounds were screened using the Lipinski five rule, and indirubin was found to be more stable toward HMG-CoA than atorvastatin. It can be concluded that the indirubin has the potential to act as an antihyperlipidemic drug.
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The aim of this study is to analyze the types of secondary metabolite compounds found in cistanche (Cistanche deserticola) plants. Methanolic extracts of callus tissues and shoots (stolon) of cistanche were obtained by lyophilic drying and grinding to powdered state using 80% methanol. Secondary metabolites within cystanche callus were first identified by GC-MS (gas chromatography-mass spectroscopy). The identification results of the methanolic extracts revealed various types of compounds including fatty acids (hexadecanoic acid, methyl ester); phenolic compounds and their derivatives (phenol, 2,4-bis(1,1-dimethylethyl)-, 2-methoxy-4-vinylphenol, homovanillyl alcohol, phenol, 2,6-dimethoxy;) sterols (γ-sitosterol); sugars, glycosides and other carbohydrates (ethyl α-D-glucopyranoside, sucrose), glycols and their derivatives (tetraethylene glycol, diethylene glycol monodododecyl ether), etc. Some of the detected compounds may be precursors or by-products of phenylethanoid glycosides biosynthesis. We also found a correlation between callus color and its chemical composition of secondary metabolites. The data can be used for further optimization of C. deserticola cultivation methods to increase the content of target secondary metabolites.
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Phytosterols are recognized for their cholesterol-reducing effects and are commonly used as dietary supplements or added to foods due to their potential cardiovascular benefits. However, evidence regarding the impact of phytosterol supplementation on inflammatory markers remains inconclusive. This systematic review and meta-analysis aim to evaluate the effect of phytosterols in reducing levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP). A systematic literature search of the primary databases was conducted up to May 2024 to identify eligible studies. The measurement of effect sizes was determined using WMD (weighted mean difference) and 95% CI. For the meta-analysis, 14 publications (19 study arms) for hs-CRP and 10 publications (16 study arms) for CRP were included. The pooled analysis showed that the administration of phytosterol did not significantly reduce CRP compared to control with WMD= -0.04 mg/l (95% CI: -0.28 to 0.20, P = 0.74). However, phytosterol supplementation significantly decreased the hs-CRP level compared to the control group with WMD of -0.25 mg/l (95% CI: -0.42 to -0.07, P = 0.006). The WMD for hs-CRP reduction was − 0.36 mg/l (95% CI: -0.53 to -0.18, P < 0.001) for supplementation with a phytosterol dose ≥ 2000 mg/day compared to the control group. Phytosterol supplementation may be effective in reducing hs-CRP levels.
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Functional foods are known not only for their nutritional value but also for their positive effects on health. Compared to traditional foods, functional foods enhance individuals' overall quality of life, promoting a more balanced mood. This study aims to systematically analyze the effects of functional foods on mood, stress, depression, and other mental health conditions and to evaluate this from a gastronomy perspective. Understanding the impact of functional foods on mental health is essential for improving individuals' quality of life and fostering healthier societies. Additionally, evaluating this issue from a gastronomic perspective is crucial to increasing the consumption of these foods. The study involved a comprehensive review of research conducted in the past ten years, using the keywords "functional foods" and "mental health" in the Web of Science (WOS) academic database. After identifying the effects of functional foods on mental health from the existing literature, the subject was further explored through gastronomy. The study concludes that more research is needed in gastronomy to promote the societal use of functional foods, which significantly impact mental health.
Chapter
In recent years, the use of renewable raw materials and natural biopolymers has increased significantly to overcome the issues associated with environmental pollution and dwindling fossil fuel resources. Lipids and proteins are inexpensive, renewable raw materials, which are considered ideal feedstock for the development of a variety of functional materials. This book provides an international viewpoint on recent developments in the utilisation of lipids and proteins together, for the development of functional materials in food engineering, environmental and industry applications. This book presents the cutting-edge research in the utilization of lipids and proteins in food, cosmetics, therapeutics, food packaging, water remediation, biofuels, lubricants, biomaterials, and composite preparations. Researchers, scientists, engineers and students working on lipids and proteins derived materials will benefit from this book, which is highly application oriented. Focusing on the latest developments in the field, this will be the first book to describe lipids and proteins together, allowing it to act as a single reference for researchers working in this area.
Chapter
This chapter explores the multifaceted role of lipids in promoting health and well-being through their incorporation into functional foods and nutraceutical formulations. Lipids, traditionally known for their energy storage function, have emerged as essential components with diverse biological activities that extend beyond mere calorie sources. This chapter delves into the various lipid classes, including fatty acids, triglycerides, phospholipids and sterols, elucidating their potential therapeutic applications in preventing and managing chronic diseases. The chapter also addresses challenges related to the incorporation of lipids into functional foods and nutraceuticals, including issues of stability, bioavailability and taste.
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La quinoa (Chenopodium quinua), al igual que otros cereales, puede emplearse para la obtención de medicamentos y productos con gran valor nutricional. El objetivo de esta investigación fue caracterizar el contenido de polifenoles y la capacidad antioxidante de diez variedades de aceite de quinua, Blanca Junín, INIA 433, Hualhuas, Blanca criolla, Salcedo, Mantaro, Chupaca, Huancayo, Rosada Junín, Pasankalla, determinando sus propiedades fitoquímicas para su posible aplicación alimentaria e industrial. Los resultados revelaron una variabilidad significativa en los niveles de polifenoles entre las distintas variedades, se destacó Blanca Criolla (33.94±0.07 mg/g) por su alto contenido de polifenoles y una notable capacidad antioxidante; en contraste, la variedad INIA-433 (28.27± 0.05mg/g) presenta la menor cantidad de estos compuestos. Se comprueba una correlación positiva, significativamente alta, entre la capacidad antioxidante y el contenido de polifenoles, lo que fortalece la confiabilidad de los métodos de evaluación utilizados en las variedades de aceite de quinua examinadas. Se resalta la relevancia de seleccionar variedades con altos niveles de polifenoles para aplicaciones que busquen propiedades antioxidantes.
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Background: Phytosterol feeding in human clinical trials has had generally small and inconsistent effects on serum cholesterol concentrations, raising doubts about the importance of phytosterols in natural diets and supplements. Objective: The hypothesis tested was that the low intestinal bioavailability of purified phytosterols can be increased by formulation with lecithin. Design: The ability of sitostanol to reduce cholesterol absorption was measured directly by including hexadeuterated cholesterol tracer in a standard test breakfast and measuring plasma tracer concentration 4 and 5 d later by gas chromatography–negative ion mass spectrometry. The tracer amount after a test meal containing sitostanol was compared with that after an identical meal containing placebo. Each subject served as his or her own control and the order of testing was random. Sitostanol was formulated either as a powder or as a sonicated micellar solution with lecithin. A total of 38 single-meal tests were performed in 6 healthy subjects. Results: Sitostanol powder (1 g) reduced cholesterol absorption by only 11.3 ± 7.4% (P = 0.2), confirming in vitro data showing poor solubility of sitostanol powder in artificial bile. In contrast, sitostanol in lecithin micelles reduced cholesterol absorption by 36.7 ± 4.2% (P = 0.003) at a dose of 700 mg and by 34.4 ± 5.8% (P = 0.01) at a dose of 300 mg. Conclusions: Sitostanol reduced cholesterol absorption at doses lower than reported previously, but only if presented in lecithin micelles. Properly formulated sitostanol as well as naturally occurring complexes of phytosterol and phospholipid might be therapeutically useful for cholesterol lowering.
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We examined, by reverse-phase high performance liquid chromatography (HPLC), the hydrophilic-hydrophobic balance of cholesterol and 12 non-cholesterol sterols and related this property to their equilibrium micellar solubilities in sodium taurocholate and sodium glycodeoxycholate solutions. Sterols investigated exhibited structural variations in the polar function (3 alpha-OH, 3 beta-OH, 3 beta-SH), nuclear double bonds (none, delta 5, or delta 7), side chain length (C27, C28, C29) and side chain double bonds (none, delta 22, or delta 24). In general, a sterol's hydrophilic-hydrophobic balance became progressively more hydrophobic (as exemplified by increasing HPLC retention values, k') with additions of side chain methyl (C28) and ethyl (C29) groups and with 3 beta-SH substitution of the 3-OH polar function. Side chain delta 22 and especially delta 24 double bonds rendered the sterols appreciably more hydrophilic, whereas a single nuclear double bond had little influence. Sterol solubilities (24 degrees C, 0.15 M Na+) were uniformly greater in 50 mM solutions of sodium glycodeoxycholate (range 0.15 to 2.5 mM) than in equimolar solutions of the more hydrophilic bile salt, sodium taurocholate (range 0.07 to 0.67 mM). For each bile salt system, a strong inverse correlation existed between micellar solubilities of sterols and their HPLC k' values, indicating that more hydrophilic sterols had greater micellar solubilities than the more hydrophobic ones. Based upon the aqueous monomeric solubilities of cholesterol (C27) and beta-sitosterol (C29) at 24 degrees C, we derived free energy changes associated with micellar binding and found that solubilization of both sterols was more energetically favored in glycodeoxycholate solutions. Although cholesterol exhibited a higher binding affinity than beta-sitosterol in glycodeoxycholate micelles, solubilization of beta-sitosterol in taurocholate micelles was more energetically favored than cholesterol by -0.6 kcal/mol. Based upon these results we offer a thermodynamic explanation for the greater micellar solubilities of more hydrophilic sterols and suggest that the high affinity, but low capacity, of a typical phytosterol for binding to trihydroxy bile salt micelles may provide a physical-chemical basis for its inhibition of intestinal cholesterol absorption.
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Most animal and human studies show that phytosterols reduce serum/or plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels. Phytosterols are structurally very similar to cholesterol except that they always contain some substitutions at the C24 position on the sterol side chain. Plasma phytosterol levels in mammalian tissue are normally very low due primarily to poor absorption from the intestine and faster excretion from liver compared to cholesterol. Phytosterols are able to be metabolized in the liver into C21 bile acids via liver other than normal C24 bile acids in mammals. It is generally assumed that cholesterol reduction results directly from inhibition of cholesterol absorption through displacement of cholesterol from micelles. Structure-specific effects of individual phytosterol constituents have recently been shown where saturated phytosterols are more efficient compared to unsaturated compounds in reducing cholesterol levels. In addition, phytosterols produce a wide spectrum of therapeutic effects in animals including anti-tumour properties. Phytosterols have been shown experimentally to inhibit colon cancer development. With regard to toxicity, no obvious side effects of phytosterol have been observed in studies to date, except in individual with phytosterolemia, an inherited lipid disorder. Further characterization of the influence of various phytosterol subcomponents on lipoprotein profiles in humans is required to maximize the usefulness of this non-pharmacological approach to reduction of atherosclerosis in the population.
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To compare effects on plasma total-, LDL-, and HDL-cholesterol concentrations of margarines enriched with different vegetable oil sterols or sitostanol-ester. A randomized double-blind placebo-controlled balanced incomplete Latin square design with five treatments and four periods of 3.5 weeks. Margarines enriched with sterols from soybean, sheanut or ricebran oil or with sitostanol-ester were compared to a non-enriched control margarine. Sterol intake was between 1.5-3.3 g/d. Two thirds of the soybean oil sterols were esterified to fatty acids. Unilever Research Laboratory, Vlaardingen, The Netherlands. One hundred healthy non-obese normocholesterolaemic and mildly hypercholesterolaemic volunteers aged 45+/-12.8 y, with plasma total cholesterol levels below 8 mmol/L at entry. Plasma lipid, carotenoid and sterol concentrations, blood clinical chemistry and haematology, fatty acid composition of plasma cholesterylesters and food intake. Ninety-five volunteers completed the study. None of the margarines induced adverse changes in blood clinical chemistry, serum total bile acids or haematology. Plasma total- and LDL-cholesterol concentrations were significantly reduced by 8-13% (0.37-0.44 mmol/L) compared to control for margarines enriched in soybean oil sterol-esters or sitostanol-ester. No effect on HDL-cholesterol concentrations occurred. The LDL- to HDL-cholesterol ratio was reduced by 0.37 and 0.33 units for these margarines, respectively. Effects on blood lipids did not differ between normocholesterolaemic and mildly hypercholesterolaemic subjects. Plasma sitosterol and campesterol levels were significantly higher for the soybean oil sterol margarine and significantly lower for the sitostanol-ester margarine compared to control. Dietary intake was very similar across treatments. The fatty acid composition of plasma cholesterylesters confirmed the good compliance to the treatment. All sterol enriched margarines reduced lipid-standardized plasma alpha- plus beta-carotene levels. Plasma lycopene levels were also reduced but this effect was not significant for all products. A margarine with sterol-esters from soybean oil, mainly esters from sitosterol, campesterol and stigmasterol, is as effective as a margarine with sitostanol-ester in lowering blood total- and LDL-cholesterol levels without affecting HDL-cholesterol concentrations. Incorporation in edible fat containing products of such substances may substantially reduce the risk of cardiovascular disease in the population.
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Background: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. Objective: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. Design: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). Results: Subjects in the low- and high-sterol groups who consumed ≥80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). Conclusion: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.
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Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multi-centre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg β-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6·7 (SD 4·0) points in the β-sitosterol-treated group versus -2·1 (3·2) points in the placebo group p
Article
Cholesterol is an essential lipid for mammalian life, but a high cholesterol level can almost guarantee the eventual onset of vascular diseases and, in some cases, can lead to death. It has been shown that there is a direct connection between high cholesterol levels and vascular diseases. Some methods for lowering the serum cholesterol level, thereby preventing the development of these diseases, have been developed and those include drugs and food additives. Since both drugs and food additives act to inhibit the uptake of cholesterol, understanding the sterol absorption process is the key to understanding exactly how drugs and food additives reduce serum cholesterol levels. The major drawback of using anti-cholesterol drugs is related to their side effects, and therefore, natural food additives called plant sterols (phytosterols) have been developed as an attractive alternative.
Article
During three experimental periods, nine adults were hospitalized on a metabolic ward and fed a meal containing 500 mg of cholesterol as a component of scrambled eggs. In addition, the meal contained: 1) no additive, 2) 1 g beta-sitosterol, or 3) 2 g beta-sitosteryl oleate. Stools for the succeeding 5 days were analyzed to determine the percentage of the cholesterol in the test meal that was absorbed. The addition of beta-sitosterol resulted in a 42% decrease in cholesterol absorption; the beta-sitosteryl oleate caused a 33% reduction. These results indicate that the judicious addition of beta-sitosterol or beta-sitosteryl oleate to meals containing cholesterol-rich foods will result in a significant decrease in cholesterol absorption, with a consequent decrease in plasma cholesterol.
Article
Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multicentre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg beta-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6.7 (SD 4.0) points in the beta-sitosterol-treated group versus -2.1 (3.2) points in the placebo group p < 0.01. There was a decrease in IPSS (-7.4 [3.8] points in the beta-sitosterol-treated group vs -2.1 [3.8] points in the placebo group) and changes in urine flow parameters: beta-sitosterol treatment resulted in increasing peak flow (15.2 [5.7] mL/s from 9.9 [2.5] mL/s), and decrease of mean residual urinary volume (30.4 [39.9] mL from 65.8 [20.8] mL). These parameters did not change in the placebo group (p < 0.01). No relevant reduction of prostatic volume was observed in either group. Significant improvement in symptoms and urinary flow parameters show the effectiveness of beta-sitosterol in the treatment of benign prostatic hyperplasia.
Article
The purpose of the present study was to examine the effect of beta-sitosterol, the main dietary phytosterol on the growth of HT-29 cells, a human colon cancer cell line. In addition, the incorporation of this phytosterol into cellular membranes and how this might influence the lipid composition of the membranes were investigated. Tumor cells were grown in DMEM containing 10% FBS and supplemented with sterols (cholesterol or beta-sitosterol) at final concentrations up to 16 microM. The sterols were supplied to the media in the form of sterol cyclodextrin complexes. The cyclodextrin used was 2-hydroxypropyl-beta-cyclodextrin. The sterol to cyclodextrin molar ratio was maintained at 1:300. The study indicated that 8 and 16 microM beta-sitosterol were effective at cel growth inhibition as compared to cholesterol or to the control (no sterol supplementation). After supplementation with 16 microM beta-sitosterol for 9 days, cell growth was only one-third that of cells supplemented with equimolar concentration of cholesterol. No effect was observed on total membrane phospholipid concentration. At 16 microM beta-sitosterol supplementation, membrane cholesterol was reduced by 26%. Cholesterol supplementation resulted in a significant increase in the cholesterol/phospholipid ratio compared to either beta-sitosterol supplemented cells or controls. There was a 50% reduction in membrane sphingomyelin (SM) of cells grown in 16 microM beta-sitosterol. Additional changes were observed in the fatty acid composition of minor phospholipids of beta-sitosterol supplemented cells, such as SM, phosphatidylserine (PS), and phosphatidylinositol (PI). Only in the case of PI, was there an effect of these fatty acid changes on the unsaturation index, beta-sitosterol incorporation resulted in an increase in the U.I. It is possible that the observed growth inhibition by beta-sitosterol may be mediated through the influence of signal transduction pathways that involve membrane phospholipids.