Plant Sterols for Lowering Cholesterol Depend on Genetics

One recommendation often made for lowering cholesterol levels is to consume higher amounts of plant sterols.  You can find plant sterols in supplements such as beta-sitosterol or spreads like Benecol or SmartBalance margarine. These butter alternatives are marketed as a heart-healthy way to help you lower cholesterol and prevent cardiovascular disease (CVD).

It turns out that plant sterols probably lower cholesterol only in people with certain genetic variants. Plus, in an interesting twist, people with genetic variants that cause greatly increased plant sterol levels are actually at a higher risk of atherosclerosis and CVD.

So the question is – are plant sterols good or bad for you? The answer depends, in part, on your genes. Let’s dig into the science here so that you can make better choices than just relying on marketing garbage for your health decisions.

Cholesterol and Plant Sterols

Heart disease is the number one killer of people worldwide, and high cholesterol levels are a risk factor for heart disease. There are differing opinions about high cholesterol risks and the role of cholesterol in heart disease. Since research tends to support the link between high cholesterol levels and heart disease, stick with me here, and we can discuss the complexity later.

In general, high triglycerides and high LDL cholesterol levels are something that most doctors will worry about. Recommendations for dietary interventions often include limiting saturated fat and adding in plant sterols. [ref Trusted Source: Peer Reviewed Journal] Your genetic variants may play a bigger role in whether plant sterols will work for you (and also how much of an impact saturated fat has, but that is another article).

Background on cholesterol:

Cholesterol is a general term for a type of lipid known as a sterol that is present in animal cells. There are several types of cholesterol made in the body, and you can also consume cholesterol in foods.

Cholesterol is transported in the blood attached to a lipoprotein – such as very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL),  high-density lipoprotein (HDL) and chylomicrons.  LDL particles are the most common cholesterol carriers.

What does cholesterol do?

Cholesterol is used by all the cells in the body as part of the cell membrane. Within the cell membrane, cholesterol can stabilize the membrane, causing less fluidity in the phospholipid bilayer.

Detail of cell membrane. Cholesterol shown in yellow. (Public domain image)

Cholesterol is also a precursor molecule for vitamin D, bile acids, and steroid hormones. While often demonized as something ‘bad’, cholesterol is essential for your body to function.

Regulation of cholesterol:

In general, the body tightly regulates the level of cholesterol that is present at any given time. If you eat more cholesterol, your liver should make less of it. If you don’t eat many foods containing cholesterol, your body will increase cholesterol production.

Bile acids are created using cholesterol that is oxidized by the liver and then bound to glycine, taurine, or sulfate molecules. Your body uses bile acids to break down and digest fats from foods, and then the bile acids are mostly reabsorbed in the intestines and recycled. Some cholesterol, though, is lost each day via excretion of bile acids through the colon.

Cholesterol from food:

Almost all of the cholesterol that you get via your diet is from animal-based foods. The cholesterol that you eat gets absorbed into the cells lining the small intestines, and people vary in how much cholesterol they absorb. There are a couple of different transporters involved in moving cholesterol from the intestinal cells. Plus, not all cholesterol from food ends up being absorbed and used by the body.  [ref Trusted Source: Peer Reviewed Journal]

Plant sterols:

Most plants produce very, very little cholesterol.[ref Trusted Source: Peer Reviewed Journal] Instead, they contain a type of sterol known as phytosterols, which is a term that covers both plant sterols and plant stanols. Plant sterols, such as sitosterol, function similarly to cholesterol in the way that they regulate the fluidity of the cell membrane.

In general, people can absorb about 5% of dietary plant sterols. Phytosterols aren’t able to be used in humans (or other mammals).

It is estimated that people generally consume 200-400 mg/day of plant sterols, but that is going to vary widely depending on your diet (e.g. vegan vs carnivore vs mixed). A recent study found that vegans had the highest plant sterol intake and lowest cholesterol intake – and this was opposite from people eating an omnivore diet (low plant sterols, higher cholesterol). Interestingly, all the dietary pattern groups had similar blood cholesterol levels and sterol levels, showing that intake may not make much of a difference from the diet. [ref Trusted Source: Peer Reviewed Journal]

Plant sterols lower cholesterol levels:

Quite a few studies are showing in an average population group increasing plant sterols will decrease cholesterol levels.

The cholesterol-lowering effect in an average population increases as the dose of plant sterols increases – up to about 2 -3g/day. [ref Trusted Source: Peer Reviewed Journal] An intake of around 2g/day of plant sterols is associated with an average decrease in LDL cholesterol of about 10%. [ref Trusted Source: Peer Reviewed Journal]

Phytosterols reduced the intestinal absorption of cholesterol because they compete with cholesterol and block it. It is thought that this lower intestinal absorption includes both dietary cholesterol and the recycling of cholesterol in bile acids.[ref Trusted Source: Peer Reviewed Journal]

Phytosterols have also been associated with a reduction in triglycerides in patients with high triglyceride levels. [ref Trusted Source: Peer Reviewed Journal]

Do plant sterols reduce cardiovascular disease?

That is the big question…  and one that is not as well answered as I would like.

Some studies show that phytosterols reduce LDL and non-HDL cholesterol, which reduced arterial stiffness (important in cardiovascular health). [ref Trusted Source: Peer Reviewed Journal]  Margarine that contains rapeseed-sterols (canola) reduced cholesterol levels and also reduced E-selectin concentrations, which is a cellular adhesion molecule important in the arteries and atherosclerosis.[ref Trusted Source: Peer Reviewed Journal]

A long-term study of plant sterol consumption (2.5 g/day for 85 weeks) showed that LDL cholesterol dropped, but this didn’t have a significant effect (positive or negative) on smaller blood vessel function. The study didn’t include very many participants in it, which would make getting a significant effect difficult. [ref Trusted Source: Peer Reviewed Journal]

Could plant sterols have the opposite effect and increase the risk of cardiovascular disease?

Something that you don’t see mentioned in the marketing literature for plant sterols is the link with increased atherosclerosis and an increased risk of heart disease for some people, depending on their genetic variants.

There are really rare genetic mutations that cause a condition known as sitosterolemia. People with the rare mutations in the ABCG5 or ABCG8 genes absorb between 15 and 60% of phytosterols from their diet (compared with the normal 5% or so).  The ABC genes code for proteins known as ATP-binding cassette transporters, which move substances – in this case, phytosterols – out of the cell. ABCG5 and ABCG8 code for the proteins that make up the sterolin transporter that pumps the absorbed plant sterols back into the intestines.[ref Trusted Source: Peer Reviewed Journal] These transporters may also be important in moving cholesterol back into the intestines as well.

So what happens with high absorption of plant sterols in sitosterolemia? Atherosclerosis can start as early as childhood, and some people develop xanthomas, which are yellowish growths that contain cholesterol. People with sitosterolemia can also have joint pain and hemolytic anemia. [ref Trusted Source: Peer Reviewed Journal]

While the negative effects of building up high amounts of plant sterols are clear, the question remains whether this is a spectrum… is there a point that a person without a rare genetic mutation can have negative effects from a higher intake of plant sterols?

A study came out about 10 years ago, showing that higher levels of sitosterol and campesterol (the most common phytosterols) were linked to an almost doubled risk of cardiovascular disease. The study participants all had a similar dietary intake of macronutrients as well as omega-6 fatty acid levels. The study concluded overall increased absorption (cholesterol, plant sterols) was associated with cardiovascular disease. [ref Trusted Source: Peer Reviewed Journal]

Several other studies also claim that the link between elevated plant sterols and coronary artery disease is due to overall cholesterol absorption and alterations to endogenous production. [ref Trusted Source: Peer Reviewed Journal]

On the other hand, animal studies show that elevated plant sterols (stigmasterols), causes cardiovascular disease even while reducing LDL cholesterol.[ref Trusted Source: Peer Reviewed Journal]

It could be that a specific type of plant sterol or oxidation of plant sterols is what elevates cardiovascular disease. Patients with higher oxidized plant sterol levels had an increase in ‘cardiovascular events’. [ref Trusted Source: Peer Reviewed Journal]

Overall, the FDA, European Food Safety Authority,  and Health Canada have decided that food products with higher plant sterol levels can be labeled as being good for reducing cardiovascular disease.  [ref Trusted Source: Peer Reviewed Journal]  There was a nine-part study done that showed that plant sterol consumption is non-toxic and doesn’t cause cancer in animals. [ref ](Studies done by Unilever, manufacturer of products with plant sterols)


Genetics, Sterols, and Lowering Your Cholesterol:

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Studies on plant sterols, stratified by genetic polymorphisms:

Variants that impact whether plant sterols lower cholesterol:

CYP7A1 gene: codes for an enzyme important in bile acid synthesis

Check your genetic data for rs3808607 (23andMe v4, v5; AncestryDNA):

  • T/T: no cholesterol-lowering benefit from plant sterols[ref Trusted Source: Peer Reviewed Journal]
  • G/T: plant sterols may help lower cholesterol
  • G/G: plant sterols may help lower cholesterol.

Members: Your genotype for rs3808607 is .

Variants that impact plant sterol effect on triglycerides:

CETP gene: codes for the cholesterol ester transfer protein

Check your genetic data for rs5882 (23andMe v4, v5; AncestryDNA):

  • A/A: no triglyceride lower effect from plant sterols [ref Trusted Source: Peer Reviewed Journal]
  • A/G: no triglyceride lower effect from plant sterols [ref Trusted Source: Peer Reviewed Journal]
  • G/G: plant sterols shown to lower triglycerides

Members: Your genotype for rs5882 is .

Variants that impact whether more plant sterols are absorbed (CVD risk?):

ABCG8 gene: codes for part of the transporter that moves plant sterols from the intestinal cells back into the intestines for excretion. Some variants increase the absorption of plant sterols and some decrease the absorption of plant sterols. Where there is also research indicating an increase or decrease in cardiovascular disease (CVD), it is indicated as well.

Check your genetic data for rs41360247 (23andMe v4, v5; AncestryDNA):

  • T/T: typical (most common)
  • C/T: reduced phytosterol levels, somewhat reduced risk of coronary artery disease [ref Trusted Source: Peer Reviewed Journal]
  • C/C: reduced phytosterol levels, somewhat reduced risk of coronary artery disease [ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs41360247 is .

Check your genetic data for rs4245791 (23andMe v4, v5; AncestryDNA):

  • C/C: increased plant sterol absorption, slightly increased CVD[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]
  • C/T: intermediate
  • T/T: typical (most common)

Members: Your genotype for rs4245791 is .

Check your genetic data for rs4148217 Thr400Lys (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • A/C: reduced risk of heart disease
  • A/A: reduced risk of heart disease [ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs4148217 is .

Check your genetic data for rs4299376 (23andMe v4, v5; AncestryDNA):

  • T/T: typical
  • G/T: increased risk of heart disease
  • G/G: increased risk of heart disease [ref Trusted Source: Peer Reviewed Journal] increased cholesterol and plant sterol absorption[ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs4299376 is .

Check your genetic data for rs11887534 D19H (23andMe v4 only):

  • G/G: typical
  • C/G: increased susceptibility to coronary artery disease (CAD); increased risk of gallstones,
  • C/C: increased susceptibility to CAD [ref]; greatly increased risk of gallstones[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs11887534 is .

Check your genetic data for rs137854891 (AncestryDNA only):

  • C/C: typical
  • C/G: carrier of a rare mutation for sitosterolemia
  • G/G: sitosterolemia (pathogenic)[ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs137854891 is .

Check your genetic data for rs199689137 (AncestryDNA only):

  • G/G: typical
  • A/G: carrier of a rare mutation for sitosterolemia
  • A/A: sitosterolemia (pathogenic)[ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs199689137 is .

Check your genetic data for rs119479065 (AncestryDNA only):

  • G/G: typical
  • A/G: carrier of a rare mutation for sitosterolemia
  • A/A: sitosterolemia (pathogenic)[ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs119479065 is .

Check your genetic data for rs137854891 (AncestryDNA only):

  • C/C: typical
  • C/G: carrier of a rare mutation for sitosterolemia
  • G/G: sitosterolemia (pathogenic)[ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs137854891 is .

Check your genetic data for rs137852987 (23andMe v4; AncestryDNA):

  • G/G: typical
  • A/G: carrier of a rare mutation for sitosterolemia
  • A/A: sitosterolemia (pathogenic)[ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs137852987 is .

ABCG5 gene: codes for the other part of the transporter that decreases the absorption of plant sterols

Check your genetic data for rs6720173 Q604E (AncestryDNA only):

  • G/G: typical
  • C/G: 4-fold greater decrease in LDL with plant sterol consumption[ref Trusted Source: Peer Reviewed Journal]
  • C/C: 4-fold greater decrease in LDL with plant sterol consumption[ref Trusted Source: Peer Reviewed Journal]

Members: Your genotype for rs6720173 is .


Lifehacks:

You should decide – based on your genetic variants – whether you think that increasing plant sterols is good for you. There seemed to be a lot of assumptions and biases (e.g. industry sponsorship) in some of the studies on phytosterols. To be perfectly honest, I don’t understand the nuances well enough to make a good judgment on which studies are skewing their data.

The research does seem to clearly show that for people with the normal CYP7A1 variant, increasing plant sterols to around 2g/day will decrease LDL cholesterol levels. If you were looking for a way to reduce LDL numbers before a blood test, this may work for you. The question, in my mind, is whether that decrease in LDL cholesterol makes a difference in cardiovascular disease risk (and whether long-term plant sterol supplementation would possibly increase CVD risk for some people).

Foods high in plant sterols:

Common foods that are high in phytosterols include oils (e.g. sunflower, canola, hemp, safflower, sesame, olive, cottonseed), avocados, raw peas, pistachios, cashews, macadamia nuts, and almonds. [ref][ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]

Phytosterol enriched foods are also available for the consumer. They range from low-fat yogurt and milk to mayonnaise and chocolates.

Beta-sitosterol is available as a supplement and in foods such as the butter-alternative spreads that are marketed as containing plant sterols. (Read the rest of the ingredients, though, on the butter alternatives to make sure they are something you want in your diet.)More to read: ABCG5 and ABCG8: more than a defense against xenosterols



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.