Throughout human evolution, plant foods have been a significant part of the human diet. These foods are rich in fiber, plant protein, and phytosterols, plant-derived compounds that are structurally similar to cholesterol. While cholesterol is the predominant sterol in animals, including humans, plants contain a variety of sterols. This article explores the role of plant sterols and stanols in our diet, their impact on cholesterol levels, and their potential health benefits.
Understanding Sterols and Stanols
Cholesterol in human blood and tissues comes from the diet and endogenous cholesterol synthesis. However, all phytosterols in human blood and tissues are derived from the diet because humans cannot synthesize them. Plant sterols have a double bond in the sterol ring, while plant stanols lack this double bond. Plant sterol or stanol esters are plant sterols or stanols esterified by creating an ester bond between a fatty acid and the sterol or stanol. This esterification, occurring in intestinal cells and industrially, makes plant sterols and stanols more fat-soluble, allowing easy incorporation into fat-containing foods like margarines and salad dressings.
How Sterols and Stanols Affect Cholesterol Absorption
Dietary cholesterol must be incorporated into mixed micelles to be absorbed by enterocytes, the cells lining the intestine. Mixed micelles are mixtures of bile salts, lipids, and sterols formed in the small intestine after consuming a fat-containing meal. The intestinal cholesterol transporter, Niemann Pick C1-Like 1 (NPC1L1), mediates transport across the apical membrane of enterocytes and is also involved in phytosterol uptake.
Inside the enterocyte, cholesterol is esterified by intestinal acyl-coenzyme A (CoA) cholesterol acyltransferases (ACATs) and incorporated into triglyceride-rich lipoproteins called chylomicrons, which are secreted into the intestinal lymphatics. The thoracic lymphatic duct collects the lymph before draining into the systemic blood circulation. As circulating chylomicrons become depleted of triglycerides, they become chylomicron remnants, which the liver takes up.
Although varied diets typically contain similar amounts of phytosterols and cholesterol, serum phytosterol concentrations are usually much lower than serum cholesterol concentrations in humans. Less than 5% of dietary plant sterols and less than 0.5% of dietary plant stanols are systemically absorbed, compared to about 50%-60% of dietary cholesterol.
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Like cholesterol, phytosterols must be incorporated into mixed micelles before being taken up by enterocytes. Once inside the enterocyte, the activity of an efflux transporter, consisting of ATP-binding cassette (ABC) proteins ABCG5 and ABCG8, inhibits the systemic absorption of phytosterols. ABCG5 and ABCG8 form a transporter that secretes phytosterols and unesterified cholesterol from the enterocyte into the intestinal lumen. Phytosterols are not as readily esterified as cholesterol within the enterocyte, so they are incorporated into chylomicrons at much lower concentrations. Those that are incorporated into chylomicrons enter the circulation and are taken up by the liver. Once inside the liver, hepatic ABCG5/G8 transporters rapidly secrete phytosterols into bile. Although cholesterol is also secreted into bile, the rate of phytosterol secretion into bile is much greater.
Cholesterol-Lowering Effects of Plant Sterols and Stanols
High intakes of plant sterols or stanols can lower serum total and low-density lipoprotein (LDL)-cholesterol concentrations in humans. Different mechanisms underlie this cholesterol-lowering effect. In the intestinal lumen, phytosterols displace cholesterol from mixed micelles and reduce cholesterol absorption. Phytosterols might also interfere with the esterification and incorporation of cholesterol into chylomicrons inside the enterocytes.
A placebo-controlled, cross-over trial showed that consuming moderate (0.46 g/day) and high (2.1 g/day) phytosterol-enriched beverages reduced cholesterol absorption by about 10% and 25%, respectively. Moderate and high phytosterol intakes also significantly increased the excretion of biliary and dietary cholesterol in the feces by 36% and 74%, respectively. Phytosterols might facilitate cholesterol efflux from peripheral tissues and macrophages lining vessel walls, transporting cholesterol to the liver for incorporation into bile stored in the gallbladder.
A decrease in intestinal-derived cholesterol entering the circulation as chylomicrons triggers the endogenous production of cholesterol to maintain cholesterol homeostasis. Cell surface LDL-receptor expression is also up-regulated to enhance the receptor-mediated uptake of circulating LDL-cholesterol into cells, increasing the clearance of circulating LDL from the blood. Within the cells, LDL particles are dismantled in lysosomes, and cholesterol becomes available for metabolic needs. Through inhibiting the sterol regulatory element-binding protein (SREBP) pathway, LDL and LDL-derived cholesterol then suppress the transcription of the genes coding for 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase and other enzymes involved in the synthesis of cholesterol and the LDL-receptor.
Potential Health Benefits Beyond Cholesterol Reduction
Experiments in cell culture and animal models suggest that phytosterols might have biological activities unrelated to cholesterol lowering. Cholesterol is an important structural component of mammalian cell membranes. The displacement of cholesterol with phytosterols has been found to alter the physical properties of cell membranes in vitro, which could potentially affect signal transduction or membrane-bound enzyme activity.
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Limited evidence from an animal model of hemorrhagic stroke suggested that very high intakes of phytosterols could displace cholesterol in red blood cell membranes, decreasing deformability and potentially increasing fragility. Limited evidence from animal studies suggests that very high phytosterol intake could alter testosterone metabolism by inhibiting 5-α-reductase, a membrane-bound enzyme that converts testosterone to dihydrotestosterone, a more potent metabolite. It is not known whether phytosterol consumption alters testosterone metabolism in humans.
Phytosterols have been found to inhibit proliferation, induce apoptosis, and reduce the invasiveness of cancer cells in culture. Limited data from cell culture and animal studies suggest that phytosterols may attenuate the inflammatory activity of immune cells, including macrophages and neutrophils.
Dietary Intake and Food Sources
Typical diets across different populations provide 150 to 450 mg/day of naturally occurring phytosterols. Vegetarian diets and food products enriched with phytosterols can help achieve much greater intakes. Elevated LDL-cholesterol concentration is a well-established risk factor in developing atherosclerosis and coronary heart disease.
Numerous clinical trials have found that daily consumption of foods enriched with free or esterified forms of plant sterols or stanols lowers concentrations of serum total and LDL-cholesterol. This evidence has been summarized in several meta-analyses combining the results of randomized controlled trials. A dose-dependent relationship was reported between total phytosterol intake levels (from less than 1 g/day to 4 g/day) and LDL-cholesterol reduction in a recent meta-analysis of 124 human studies. When analyzed separately, plant sterols and stanols showed similar dose-response effects on LDL-cholesterol concentrations for average doses ranging from 0.6 g/day to 3.3 g/day. Another meta-analysis that analyzed the results of 59 randomized controlled trials suggested that reductions in LDL-cholesterol were greater in those with higher baseline concentrations of LDL-cholesterol.
Interestingly, a recent meta-analysis of 15 randomized controlled trials investigating the effects of phytosterol-enriched food intake (1.8 to 6 g/day of phytosterols) in patients treated with statins (drugs that inhibit endogenous cholesterol synthesis) found that co-administration of phytosterols and statins significantly reduced total cholesterol and LDL-cholesterol concentrations compared to statin therapy alone. The concentrations of HDL-cholesterol and triglycerides were unaffected by the combination of phytosterols and statins compared to statin alone.
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Impact on Vascular Health
Impairment of vascular endothelial function is considered an early step in the development of atherosclerosis and cardiovascular disease. A recent 12-week randomized, double-blind, placebo-controlled study in 240 subjects with hypercholesterolemia (serum cholesterol ≥5 mmol/L [≥193 mg/dL]) found no effect of consuming 3 g/day of phytosterols added to low-fat spread on brachial artery flow-mediated dilation (FMD), a surrogate marker of endothelial health. Assessment of arterial stiffness - using measures of aortic pulse wave velocity (PWV) and augmentation index (AI) - and blood pressure also showed no difference between supplemented and placebo groups, despite a significant 6.7% reduction in total and LDL-cholesterol.
Other trials in individuals with hypercholesterolemia and type 1 diabetes mellitus also failed to find an effect of phytosterol-enriched spread consumption on brachial artery diameter, FMD, and/or arterial stiffness. Nonetheless, the results of a randomized controlled trial in 92 individuals of whom 72% had serum cholesterol ≥5 mmol/L suggested beneficial effects of plant stanol-enriched spread consumption (corresponding to 3 g/day of stanols for six months) on arterial stiffness and endothelial function, as assessed by cardio-ankle vascular index (CAVI) and reactive hyperemia index (RHI) measures, respectively. Finally, a 21-month randomized controlled trial used retinal photography to examine the effect of phytosterol-enriched margarine consumption on retinal microcirculation in 43 statin-treated subjects. Reductions in LDL-cholesterol concentration by 9.7% and 11.2% with plant sterols (2.5 g/day) and plant stanols (2.5 g/day), respectively, were not accompanied by significant changes in the diameter of retinal arterioles and venules, a proxy measure to assess microvascular health. At present, whether phytosterols can improve vascular health in individuals with endothelial dysfunction is unclear.
Role in Reducing Coronary Heart Disease Risk
Elevated LDL-cholesterol is an established risk factor for coronary heart disease (CHD). The pooled analysis of 27 randomized controlled trials of statin drug therapy found a 24% decrease in the risk of major coronary events and a 12% decrease in vascular mortality per 1 millimol/L (1 mM) reduction in LDL-cholesterol concentration, irrespective of gender and level of cardiovascular risk.
Adding plant sterol- or stanol-enriched foods to a heart-healthy diet low in saturated fat and rich in fruit and vegetables, whole grains, and fiber offers the potential for additive effects in CHD risk reduction. For example, following a diet that substituted monounsaturated and polyunsaturated fats for saturated fat resulted in a 9% reduction in serum LDL-cholesterol after 30 days, but the addition of 1.7 g/day of plant sterols to the same diet resulted in a 24% reduction.
The National Cholesterol Education Program (NCEP) Adult Treatment Panel III included the use of plant sterol or stanol esters (2 g/day) as a component of maximal dietary therapy for elevated LDL-cholesterol. The 2013 report of the American College of Cardiology (ACC) task force advised clinicians to consider using phytosterol-enriched foods as dietary adjuncts for high-risk patients with insufficient LDL-cholesterol response to statin therapy. However, stepping back from a general recommendation, the ACC and American Heart Association (AHA) did not include phytosterols in their 2013 report on lifestyle management guidelines to reduce cardiovascular risk.
The US Food and Drug Administration (FDA) has authorized the use of health claims on food labels indicating that regular consumption of foods enriched with plant sterol or stanol esters, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease.
Dietary Phytosterol Intake and LDL-Cholesterol Concentrations
Clinical trials finding that daily consumption of foods enriched with plant sterols or stanols can significantly lower LDL-cholesterol concentrations do not account for naturally occurring phytosterols in the diet. Relatively few studies have considered the effects of dietary phytosterol intakes on serum LDL-cholesterol concentrations. Limited evidence, primarily from cross-sectional studies, suggests that dietary phytosterols may play an important role in decreasing cholesterol absorption.
A cross-sectional study in the UK found that dietary phytosterol intakes were inversely related to serum total and LDL-cholesterol concentrations even after adjusting for saturated fat and fiber intake. Similarly, an analysis in a Swedish population found that dietary intake of phytosterols was inversely associated with total cholesterol in both men and women and with LDL-cholesterol in women. Dietary phytosterol intakes were also found to be inversely associated with LDL-cholesterol concentrations in another cross-sectional study in healthy Spanish participants. In single-meal tests, removing 150 mg of phytosterols from corn oil increased cholesterol absorption by 38%, and removing 328 mg of phytosterols from wheat germ increased cholesterol absorption by 43%.
Phytosterols and Cancer Risk
Limited data from animal studies suggest that very high intakes of phytosterols, particularly sitosterol, may inhibit the growth of breast and prostate cancer. Only a few observational studies have examined associations between dietary phytosterol intakes and cancer risk in humans. A series of case-control studies in Uruguay found that dietary phytosterol intakes were lower in people diagnosed with stomach, lung, or breast cancer than in cancer-free control groups. Case-control studies in the US found that women diagnosed with breast or endometrial (uterine) cancer had lower dietary phytosterol intakes than women who did not have cancer. In contrast, another case-control study in the US found that men diagnosed with prostate cancer had higher dietary campesterol intakes than cancer-free controls.
Practical Ways to Incorporate Plant Sterols and Stanols into Your Diet
If you’re trying to manage your cholesterol, food plays a big part. Plant sterols and stanols have an especially valuable role. These natural compounds found in certain plant-based foods both look and act like cholesterol. But eating foods that contain these compounds can help lower total cholesterol levels.
Cholesterol is a waxy substance that your liver makes. It protects nerves and makes cell tissues and certain hormones. You also get it from eating foods such as eggs, meat, and dairy products. Your body needs cholesterol, but too much of it can pose serious health risks, such as heart disease and stroke.
There are several types of cholesterol. These are the main two:
- Low-density lipoprotein (LDL) cholesterol: If you have too much LDL (“bad” cholesterol), you put yourself at risk for heart disease. It can clog your arteries.
- High-density lipoprotein (HDL): High levels of HDL (the “good” cholesterol) are a sign of health. HDL can help protect arteries and prevent fatty deposits that could clog them.
Sterols and stanols have a similar molecular structure to cholesterol. That’s how these plant compounds get in the way when your digestive system tries to absorb cholesterol. So instead of going into your bloodstream where it can clog arteries, the cholesterol leaves your body as waste, which lowers your cholesterol level.
In fact, when you get enough sterols and stanols in your diet, you can lower your total cholesterol by up to 10% and LDL cholesterol (the bad stuff) by up to 14%. They’re a key addition to a healthy diet.
According to the National Cholesterol Education Program, you need 2 grams of plant sterols and stanols a day to lower your cholesterol. You can do this by eating plenty of healthy food, such as:
- Fruits
- Vegetables
- Whole grains
- Legumes
- Nuts
- Seeds
- Vegetable oil
The amount of natural sterols and stanols in these foods is a good bit lower than the daily amount you’d need to lower your cholesterol. But some manufacturers fortify their foods with them. Adding fortified foods to your diet can help round up your daily intake. You can find added sterols and stanols, also called phytosterols, in some:
- Margarines
- Cheeses
- Orange juice
- Milk
- Bread
Read labels to look for added phytosterols.
Sterols and stanols also come as dietary supplements. Though taking supplements is better than getting no sterols or stanols in your diet at all, it’s usually better to get your nutrients naturally from whole foods when you can.
The American Heart Association recommends eating sterol and stanol fortified foods if you’re trying to lower your high cholesterol. These foods can also help if you’ve had atherosclerosis, a buildup of fats, cholesterol, and other substances on your artery walls, in the past. A healthy diet typically contains around 200-400mg of sterols and stanols a day. However, this intake is too low to bring about a significant cholesterol-lowering effect. Plant stanols and sterols are added to certain foods such as fat-based spreads or dairy-type foods like milk, yogurt, and yogurt drinks.
Plant sterols and stanols have a similar chemical structure to cholesterol. They are thought to work by reducing the absorption of cholesterol in the gut so more is lost in the feces (poo). The cholesterol-lowering effect varies between individuals. There is evidence to show that eating 2g (between 1.5g to 3g) of plant stanols and sterols can lower LDL (low-density lipoprotein) cholesterol by 7.5 to 12 percent when eaten regularly as part of a healthy diet. If you take statins (cholesterol-lowering medication), eating stanols or sterols will further lower non-HDL cholesterol.
While taking plant stanols and sterols has been shown to reduce cholesterol levels, there is insufficient long-term evidence to show that they also reduce your risk of having a heart attack or stroke. If you decide to use a plant stanol or sterol fortified product, follow the instructions on the packaging. You need to take them every day, with meals, as they work by mixing with food, and in the right amount. Stanols and sterols are also available in dietary supplements. There is less evidence for the effectiveness of the supplements compared to food containing stanols and sterols. You do not need to consume more than the maximum recommended amount.
It is not essential to take plant sterols and stanols to help manage your cholesterol. They are not a substitute for a healthy diet or a replacement for cholesterol-lowering medication. To help lower your cholesterol, it is more important to make long-term changes to your diet and lifestyle. These products are safe for people taking cholesterol-lowering medication such as statins and fibrates. Plant sterols/stanols are generally safe for most healthy people. Consuming around 2g of stanols and sterols, in combination with a healthy diet, can help lower blood cholesterol levels.