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Functional Medicine High Cholesterol Protocol

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Functional Medicine High Cholesterol Protocol

Dealing with high cholesterol can feel overwhelming, but you're not alone. It's a common concern that affects over 100 million American adults. 

Too much cholesterol, especially the bad kind, can put your heart at risk. High cholesterol increases the risk of atherosclerotic cardiovascular disease (ASCVD), heart attack, and stroke. In the United States, ASCVD afflicts 26 million people and is responsible for 400,000 deaths annually.

This guide will break down an effective step-by-step protocol to lower cholesterol and improve heart health.


Understanding Cholesterol

Cholesterol is a type of lipid. It is a waxy, fat-like substance found in every cell of your body. Although cholesterol is often demonized, the body needs it to make cell membranes, hormones, and vitamin D. Cholesterol comes from two sources:

  • Made by the liver
  • Animal-derived foods 

Lipids cannot mix with water and need escorts to travel through the blood. Lipoproteins are compounds that transport lipids, including cholesterol, in the bloodstream. Imagine cholesterol as a passenger carried through the bloodstream by lipoprotein taxis.

The liver packages cholesterol with triglycerides, another type of lipid, into very low-density lipoproteins (VLDL). As VLDL particles shuttle triglycerides to muscle and fat cells, the leftover particles change into low-density lipoproteins (LDL). (31

Low-density lipoprotein cholesterol (LDL-C) is carried by LDL to cells. LDL-C is called "bad cholesterol" because, in excess, it contributes to plaque buildup in the arteries (atherosclerosis), which can lead to:

  • Heart attack
  • Stroke
  • Aneurysm
  • Blood clots (4

High-density lipoprotein cholesterol (HDL-C), known as "good cholesterol," is transported by HDL from the cells to the liver, where it can be eliminated from the body. A higher level of HDL-C is associated with a lower risk of ASCVD.

A Step-by-Step Diagnosis

Simple tests can measure how much cholesterol is in your blood, diagnose high cholesterol, and provide insight into how your numbers impact ASCVD risk.

Basic Lipid Panel

High cholesterol is diagnosed based on numbers measured on a basic lipid panel, such as the Lipid Panel by Access Med Labs. Your doctor may recommend that you fast (no food or beverages except water) for at least nine hours before the blood draw. 

The basic lipid panel gives you the following numbers

  • Total cholesterol (TC)
  • LDL-C
  • HDL-C
  • VLDL-C
  • Triglycerides (TG)
  • Non-HDL cholesterol

Normal results are as follows:

  • TC less than 200 mg/dL
  • LDL-C less than 100 mg/dL
  • HDL-C greater than 40 mg/dL (male) or 50 mg/dL (female) 
  • Triglycerides less than 150 mg/dL 

High cholesterol is diagnosed when at least one of the following criteria is met: 

Lipoprotein Fractionation

Emerging research shows that ASCVD risk is better indicated by LDL particle size and number than LDL-C. Even patients with seemingly normal TC, LDL-C, and HDL-C levels may still be at significant cardiovascular risk, depending on their lipoprotein particle composition. 

A high concentration of small, dense LDL particles correlates to increased cardiovascular risk due to heightened penetration of arterial walls and susceptibility to oxidation. Conversely, individuals with fewer, larger, and "fluffy" LDL particles generally are at a lower risk for cardiovascular complications. (39, 47

Lipoprotein fractionation tests, such as the NMR LipoProfile by Access Med Labs, are specialized tools doctors use to get a detailed picture of circulating lipoprotein size and quantity. 

Apolipoprotein B (ApoB)

Every lipoprotein particle with atherogenic potential contains one ApoB protein. This marker provides a more accurate assessment of ASCVD risk than the traditional LDL-C measurement. ApoB is a stronger predictor of heart attack than LDL-C.

You can measure ApoB with the Apolipoprotein B (ApoB) test by BostonHeart Diagnostics.

Lipoprotein(a) [Lp(a)]

High Lp(a) levels are associated with an increased risk of ASCVD. Studies indicate that an elevation in Lp(a) is an independent risk factor for CVD. About 10-20% of individuals have high Lp(a), which is driven mainly by genetics. (35

You can measure Lp(a) with the Lipoprotein(a) (Lp(a)) test by BostonHeart Diagnostics.

Inflammatory Markers

Plaques are created when atherogenic lipoproteins accumulate in the presence of arterial inflammation. Inflammation facilitates cholesterol oxidation, the recruitment of immune cells, and, eventually, plaque formation.

High-sensitivity C-reactive protein (hs-CRP) and homocysteine can quantify arterial inflammation and stratify ASCVD risk. Multiple studies provide compelling evidence linking higher levels of hs-CRP and homocysteine to poorer cardiovascular outcomes (7, 32). 

Cardiovascular Risk Factors

When screening for other things that might affect heart health in people with high cholesterol, doctors usually look at a few key factors

  • Blood pressure: high blood pressure puts extra strain on the heart
  • Diabetes: when blood sugar levels are too high, blood vessels become damaged, and heart problems are more likely
  • Smoking habits: smoking damages blood vessels and makes heart disease worse
  • Weight and body mass index (BMI): overweight and obesity increase the risk of heart disease
  • Fam
  • ily history: an individual's risk of heart disease, heart attack, and stroke is increased if they have a parent or sibling who experienced a cardiovascular event before age 50 

Comprehensive Stool Testing

Dysbiosis, an imbalance in the gut microbiota, may contribute to cholesterol imbalances and atherosclerosis by influencing systemic inflammation, intestinal barrier function, endothelial and nervous system function, hormonal balance, and the immune system. 

A comprehensive stool analysis helps doctors screen for imbalances in the gut-heart axis that can increase CVD risk. Here are popular stool testing options at Rupa:

Thyroid Hormones

Thyroid hormones regulate the activity of enzymes involved in cholesterol synthesis. Hypothyroidism can lead to elevated cholesterol levels, as decreased thyroid function impairs the body's ability to process and eliminate cholesterol efficiently. (29

A slow thyroid can be diagnosed by measuring TSH, free T3, and free T4 with a thyroid panel, such as the Thyroid Panel Comprehensive by Access Med Labs. 

Salivary Cortisol

If stressed, you are more likely to have imbalanced lipid levels (43). Stress is positively linked to having less healthy dietary habits and a higher body weight, which are known risk factors for high cholesterol. 

Cortisol, the body's stress hormone, may be to blame by increasing abdominal obesity, increasing appetite, and perpetuating pro-inflammatory immune responses (43).

Doctors may consider ordering a multi-point salivary cortisol test for patients with high cholesterol who report high stress. An example is Genova Diagnostics' Adrenocortex Stress Profile.

Sex Hormones

Estrogen lowers LDL-C and increases HDL-C. Menopause-associated hormonal changes (i.e., low estrogen) can increase cardiovascular risk by raising blood pressure and "bad" cholesterol levels. 

Similarly, there is some evidence to suggest that low testosterone contributes to CVD and that as testosterone levels rise, cholesterol levels fall. 

Ordering a hormone panel, such as the Comprehensive Hormone Panel by Doctor's Data, can help identify hormonal imbalances contributing to unfavorable lipid variations.


Treatment Protocols

Dealing with high cholesterol can feel like navigating through a maze of confusing information, yet effective management is possible with a combination of lifestyle changes, pharmaceutical interventions, and natural remedies.

Dietary Modifications

The 2019 ACC/AHA Guidelines for managing high cholesterol and primary prevention of ASCVD emphasize a healthy diet that includes:

  • Vegetables
  • Fruits
  • Nuts
  • Whole grains
  • Lean vegetable or animal proteins
  • Minimal trans fats, red and processed meats, refined carbohydrates, and sweetened beverages 

The Mediterranean and DASH diets are evidence-based approaches for promoting cardiovascular health. Both diets prioritize whole foods and emphasize the incorporation of plant sterols and soluble fiber, which aid in the binding of cholesterol in the gastrointestinal tract for elimination from the body. 

The Mediterranean diet, featuring olive oil rich in monounsaturated fats and omega-3 fatty acids from fish, has been linked to lower LDL-C and inflammation. 

Similarly, the DASH diet, initially designed for hypertension management, focuses on plant-based foods, low-fat dairy, and lean proteins and demonstrates cholesterol-lowering effects. 


Exercise benefits for heart health include:

  • Weight management
  • Improved metabolism
  • Reducing ASCVD risk

Adults should engage in at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic activities weekly. Additionally, they should include strength training exercises 2-3 times per week. 

Stress Management

Mental stress can cause rapid elevations in cholesterol levels. Keep stress levels at bay by following these tips:

  • Practice stress reduction activities, such as meditation, deep breathing, and yoga
  • Get enough sleep. Inadequate sleep can cause inflammation, weight gain, and high blood pressure. Adults should aim for 7-9 hours of uninterrupted sleep nightly.
  • Eat a healthy diet
  • Exercise regularly
  • Avoid nicotine, caffeine, and alcohol

Cholesterol-Lowering Medications

Statin pharmacologic therapy is the first-line treatment in patients with LDL-C greater than 190 mg/dL, diabetes mellitus, 40-75 years of age, and at sufficient ASCVD risk (calculated with the ASCVD Risk Calculator). 

Other pharmacologic options for lowering cholesterol include: 

  • Ezetimibe
  • PCSK9 inhibitors
  • Bile acid sequestrants
  • Bempedoic acid (3)

Dietary Supplements

Personalized supplementation strategies can complement lifestyle modifications and medications. Individuals should always consult with healthcare providers before initiating any supplement to ensure safety and compatibility with existing health conditions or medications.

Red Yeast Rice (RYR)

RYR is made by fermenting rice and contains a natural statin-like compound called monacolin K (23). 

  • Monacolin K inhibits an enzyme involved in cholesterol synthesis, lowering LDL-C levels by 15-25% within 6-8 weeks 
  • Dose: 1,200 to 4,800 mg per day in split doses
  • Often dosed with coenzyme Q10 (CoQ10), 50-100 mg daily, to prevent statin-associated muscle pain


Niacin (vitamin B3) is one of the water-soluble B complex vitamins. 

  • Niacin reduces VLDL-C, LDL-C and TG. Niacin also increases HDL-C. 
  • Dose: Start with 250 mg at bedtime. Increase gradually by 250 mg/day up to 3,000 mg/day, divided into two or three doses.

Omega-3 Fatty Acids

Omega-3 fatty acids are a type of healthy fat, often dosed as fish or algal oil. 

  • Omega-3s exhibit TG- and hs-CRP-lowering effects
  • Icosapent ethyl (a type of omega-3 fatty acid called eicosapentaenoic acid) 2 grams twice daily reduces cardiovascular events and cardiovascular-related death by 25% and 20%, respectively. 

Probiotics & Prebiotics

Probiotics are live microorganisms that confer health benefits to the host when consumed in sufficient amounts.

  • Lactobacillus and Bifidobacterium probiotic species lower TC and LDL-C by enhancing bile acid metabolism and reducing cholesterol absorption (46, 55

Prebiotics are non-digestible fibers that promote the growth of beneficial gut bacteria.

  • Prebiotic foods include garlic, onions, and chicory
  • Prebiotics are also frequently added to probiotic supplements to enhance their efficacy
  • Studies have found that prebiotics can lower TC and TG levels

Liver Support

The liver breaks down excess cholesterol so it can be eliminated from the body. If the liver is not functioning well, cholesterol can build up. Support the liver with:

  • Antioxidant- and sulfur-rich foods
  • Milk thistle
  • Turmeric
  • Dandelion 

Hormone Support

If hormonal imbalances are implicated in high cholesterol levels, they must be addressed. Effective hormone-balancing protocols should address the production and elimination of the targeted hormone(s). Listed below are some supplements to consider in addition to a healthy diet, regular exercise, adequate sleep, and stress management:

Implementing the Protocol

Prioritize interventions based on the severity of high cholesterol, always emphasizing lifestyle modifications as first-line therapies. Consider pharmacological and supplemental interventions, if necessary, guided by individual patient profiles and tolerances. 

Regularly monitor progress by tracking lipid panels, assessing adherence to the treatment plan, and evaluating potential side effects of medications/supplements. Patient response to the treatment plan can be assessed with a repeat lipid panel 4-12 weeks after initiating the protocol. Adjust the protocol as needed based on patient response.


Key Takeaways

  • Managing high cholesterol necessitates a holistic approach.
  • Recognizing the intricate interplay of factors contributing to cholesterol imbalances, healthcare practitioners are encouraged to embrace specialty testing and adopt a patient-centered treatment approach encompassing dietary modifications, lifestyle changes, natural supplements, and pharmacological interventions.
  • Such an approach optimizes cholesterol levels, improving cardiovascular risk and health outcomes.
The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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