Cardiovascular disease is the leading cause of death for both men and women in the United States. Arterial plaque formation and blockages result in one million heart attacks a year. Cholesterol levels are considered a key modifiable risk factor in the fight against cardiovascular disease. LDL-C, non-HDL and ApoB levels are all strongly correlated with a ten-year risk of cardiovascular mortality.

A functional medicine approach to high cholesterol takes a root-cause approach, utilizing specialty labs, an extensive intake on diet and lifestyle, and looking at genetic variations that may influence your cholesterol absorption.

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Possible Causes of High Cholesterol

Genetics plays a very significant role in an individual’s cholesterol levels. There are genetic variations in how much cholesterol is produced by the body, how much cholesterol is absorbed by the gut, and how efficiently cholesterol particles are cleared from the blood.

Recent studies have found multiple genes that affect cholesterol levels in a complex, multifactorial manner.

Lifestyle factors also play a role in high serum cholesterol. Although this association remains controversial, diets high in saturated fat may increase cholesterol in some individuals. Lack of physical exercise may also play a role in cholesterol levels, although the scientific data on this relationship is mixed.

Functional Medicine Labs to Test for High Cholesterol

Apo B

There is a growing consensus that the number of ApoB-containing lipoproteins (ApoB) is the most reliable blood marker of lipid burden and cardiovascular risk. In a very recent study, ApoB levels were the most predictive of a heart attack when compared to all other lipid metrics.

While LDL cholesterol and ApoB are often correlated, there are common clinical scenarios, such as patients with high triglycerides or diabetes, where the LDL cholesterol level may underestimate risk.

Many lipidologists and cardiologists now suggest using ApoB measurements instead of LDL when assessing lipid levels when evaluating treatment response.

Cholesterol Balance Test

The Cholesterol Balance Test provides valuable insight into the underlying pathophysiology behind an individual’s elevated cholesterol.

This test assesses cellular cholesterol production and gastrointestinal cholesterol absorption; using a proprietary lipid extraction method.

Genetic variations amongst individuals can cause them to make more intracellular cholesterol or absorb more cholesterol from the gut lumen.

Many cells in the body can produce their own cholesterol. Lathosterol and desmosterol are intracellular cholesterols markers produced in high enough amounts to be detected in the blood. Elevations in these markers were significantly associated with cardiovascular disease in the Framingham Offspring Study.

Beta-sitosterol and Campesterol are markers of the gastrointestinal absorption of cholesterol from the food we eat and the bile acids that our body uses to excrete cholesterol.

Beta-sitosterol and Campesterol are phytosterols (cholesterol-like compounds found in plants) that we absorb via our GI tract and circulate in our blood.

Boston Heart uses these phytosterols as a metric to quantify how successful the body is at absorbing sterols from the Gi tract. Rates of cholesterol absorption in the Gi tract vary widely between individuals due to genetic differences and can range from as little as 25% absorption to 80% absorption.

The Cholesterol Balance Test helps you identify which pathway is the root cause for elevated serum cholesterol and will allow you to tailor your medication or lifestyle recommendations to your unique patient.

Lp(a)

Lp(a) is a subtype of an LDL molecule with a unique lipoprotein, known as apolipoprotein(a), attached to its surface. There is increasing recognition that the number of Lp(a) particles is an independent risk factor for cardiovascular disease.

About 10-20% of individuals have elevated levels of Lp(a), likely secondary to genetic variations. Knowing whether or not a patient carries this additional cardiovascular risk factor can help a practitioner determine how aggressive they need to be when managing cardiovascular risk factors.

Functional Medicine Treatment for High Cholesterol

There are numerous effective pharmaceuticals for high cholesterol.

Statins have been the mainstay of treatment for years. They work by inhibiting the cellular production of cholesterol (i.e., lathosterol and desmosterol).

Other options, such as PCSK-9 inhibitors and Ezetimibe, have also been shown to be effective. Ezetimibe blocks the absorption of cholesterol from the gastrointestinal tract.

For patients who don’t tolerate or want to avoid medications; supplements, diet, and exercise may be a beneficial option.

Supplements That Lower Cholesterol

Red Yeast Rice

Red Yeast Rice (RYR) is one of the most effective cholesterol-lowering nutraceuticals available today. It works by lowering plasma cholesterol levels between 15%-25% within two months of starting the supplement.

The active ingredient for RYR is monacolin K which has a similar mechanism to statin medications and inhibits the HMG-CoA reductase enzyme.

Berberine

Berberine is a compound isolated from the bark, roots, rhizome, and stems of plants from the genus Berberis.

Berberine has been shown to lower lipid levels by upregulating the expression of LDL receptors and suppressing the PCSK9 enzyme, thus improving the clearance of cholesterol molecules.

Two small studies found that Berberine lowered LDL cholesterol by approximately 25% and triglyceride levels by roughly 30%. (1) (2)

‍Nutrition for High Cholesterol

There is mixed data on whether decreasing saturated fat intake improves cholesterol. Part of the discrepancy may be related to the strong effect of genetic variation in an individual’s response to dietary changes.

Genetic variations in the APOE gene have been shown to create differential responses to dietary saturated fat. Individuals who carry APOE2 and APOE4 alleles had increased cholesterol and increased cardiovascular disease in response to saturated fat compared to individuals who did not carry those alleles.

A trial of a low saturated fat diet with lab tracking of lipid markers may be worth it to identify patients who would benefit from dietary changes.  

Another dietary intervention with a more universal benefit is increasing the consumption of soluble fiber. Both European and US guidelines recommend consuming soluble fiber from grains such as oats to lower serum cholesterol.

A meta-analysis of 12 randomized controlled studies found that consuming greater than 3 grams of soluble fiber per meal lowered total cholesterol by 0.13 mmol/L.

A more recent meta-analysis showed a more significant benefit with a 0.25 mmol/L reduction in LDL and a 0.30mmol/L reduction in total cholesterol with the consumption of > 3 grams of soluble fiber. Foods such as beans, fruits, vegetables, nuts, and whole grains such as oats and barley are all fantastic sources of soluble fiber.

Exercise for High Cholesterol

High-intensity exercise has been shown to improve lipid profiles; however, recently, the effectiveness of low- to moderate-intensity exercise has been studied for sedentary individuals with higher LDL levels. One study reviewed results from 11 randomized controlled trials. All studies ultimately showed that low- to moderate-aerobic exercise intensities positively affected LDL subfractions.

With all of the health benefits associated with daily movement, it is easy to recommend increasing an individual’s activity to see if it affects their cholesterol levels.

Summary

Managing cardiovascular risk is a crucial component of preventative care. High cholesterol is a modifiable risk factor that may respond to multiple interventions. Using ApoB, Lp(a), and the cholesterol balance test, you can provide patients with a nuanced assessment of their personal cardiovascular risk and create a treatment regimen tailored to their specific pathophysiology.

There are numerous medications available today that effectively lower cholesterol, but there are also supplements and lifestyle factors that you can utilize to help patients reach their cholesterol goals and stay healthy.