Severe High Triglycerides and Familial Chylomicronemia Syndrome
- Acute Pancreatitis
- Recurrent Acute Pancreatitis
- Chronic Pancreatitis
- Autoimmune Pancreatitis
- Familial Chylomicronemia Syndrome
- Pediatric Pancreatitis
What are Triglycerides?
Triglycerides are a type of fat that circulate in the blood and serve as an essential energy source for the body. The body gets triglycerides from food, and excess calories the body doesn’t immediately use are converted into triglycerides and stored in fat cells. When energy is needed, these triglycerides are released to fuel the body. While triglycerides play an essential role in maintaining good health, having high levels in the blood can increase the risk of heart disease, stroke, and other diseases, including pancreatitis.
Triglyceride Ranges
Triglycerides are measured with a blood test, and the levels fall into different categories:
| Level | Triglycerides | |
| mg/dL | mmol/L | |
| Optimal | <100 | <1.1 |
| Normal | <150 | <1.7 |
| Borderline-high triglycerides | 150-199 | 1.7-2.3 |
| High Triglycerides | 200-499 | 2.3-5.6 |
| Severe | >500 | >5.6 |
| >880 Chylomicronemia | >9.9 | |
Triglycerides travel through the blood in particles such as VLDL and chylomicrons. Normally, enzymes break down triglycerides for energy, but when triglycerides get too high, chylomicrons carrying triglycerides may build up in the blood, leading to health problems.
Severe Hypertriglyceridemia (sHTG)
sHTG refers to dangerously high levels of triglycerides, typically above 880-1,000 mg/dL, and especially >2,000 mg/dL in very severe cases. High triglyceride levels can put you at risk for health complications like acute pancreatitis, a painful and sometimes life-threatening inflammation of the pancreas.
What Causes Severe Hypertriglyceridemia
The causes of Severe Hypertriglyceridemia (SHTG) typically fall into three categories:
Familial Chylomicronemia Syndrome (FCS)
FCS is a rare inherited disorder that causes extremely high triglycerides from a young age due to defective fat metabolism. It affects 1–13 in a million people and is a rare form of sHTG.
Multifactorial Chylomicronemia Syndrome (MCS)
(More common than FCS)
MCS results from a combination of genetic factors and lifestyle or other health conditions.
Secondary Hypertriglyceridemia
This type occurs due to an underlying condition or external trigger. It may be temporary or reversible.
Severe Hypertriglyceridemia and Pancreatitis Risk
When triglyceride levels get extremely high, the blood becomes thick and sticky. This can block small blood vessels in the pancreas, leading to inflammation, known as acute pancreatitis.
Over time, this can cause permanent damage and lead to:
- Chronic pancreatitis: long-term inflammation
- Diabetes: because the pancreas produces insulin that helps control blood sugar
- Pancreatic exocrine insufficiency: because the pancreas produces enzymes for digestion and it cannot do that well when the pancreas stops working properly
Read more on Acute Pancreatitis
Familial Chylomicronemia Syndrome (FCS)
Familial chylomicronemia syndrome (FCS) is a rare genetic disorder that affects around 1-13 people per million.
People with FCS can’t properly break down triglycerides because of a problem with an enzyme called lipoprotein lipase (LPL). FCS symptoms often start in early childhood or young adulthood, but they can start at any age.
Key Features of FCS
- Genetic condition: not caused by diet or lifestyle
- Persistent high triglycerides: levels stay high regardless of triglyceride-lowering medications or diet.
- Early onset: symptoms tend to begin in childhood, adolescence, or early adulthood.
Genetics of Familial Chylomicronemia Syndrome
FCS is caused by mutations (changes) in genes that help break down triglycerides. The most common mutation happens in the LPL gene, but other associated genes include:
- LPL (most common)
- APOA5
- APOC2
- GPIHBP1
- LMF1
- CREB3L3
Symptoms of Familial Chylomicronemia Syndrome:
People with FCS may experience:
Recurring Abdominal Pain
Repeated Episodes of Pancreatitis
Numbness in the Feet or Legs
Milky-looking blood (Lipemia Retinalis): veins in the retina appear milky due to high blood triglycerides.
Extremely High Triglyceride Levels
Fatigue and Brain Fog
Vomiting and Diarrhea
Fatty Skin Bumps (Eruptive Xanthomas): small, yellowish bumps on the skin caused by fatty deposits.
Diagnosing Familial Chylomicronemia Syndrome
There is no single test for FCS. Doctors consider a combination of factors:
Severe fasting triglyceride levels
>880 mg/dL on multiple occasions
History of Recurrent Abdominal Pain
History of Acute Pancreatitis
Genetic Testing for FCS-related mutations
Ruling out Secondary Causes
e.g., diabetes, hypothyroidism, medications, or excessive alcohol use
Identifying FCS early helps prevent serious complications, including pancreatitis and long-term pancreatic damage.
Treating Familial Chylomicronemia Syndrome
There is no cure for FCS, but dietary management, emerging medications, and a multidisciplinary care team can help reduce complications.
Diet Changes
People with FCS cannot properly digest triglycerides and fats. To prevent health complications, it is important to follow a very low-fat diet to keep triglycerides under control.
General Dietary Recommendations
- Limit fat intake to 10%-15% of daily calories (~15 – 30g per day) and use medium-chain triglyceride (MCT) oil as needed
- Avoid alcohol and sugar, which can raise triglycerides
- Eat small, frequent meals to help with digestion and reduce spikes
- Take supplements for essential fat-soluble vitamins (A, D, E, K)
- Get 2-4% of daily calories from essential fatty acids omega-3 and omega-6
Essential Fatty Acids & Food Sources
The body cannot make two key fatty acids, so they must come from food:
- Omega-3 (ALA): found in chia seeds, flaxseeds/flaxseed oil, walnuts/walnut oil, soybeans, and tofu.
- Omega-6 (LA): found in whole grains.
Always consult a healthcare provider before making any dietary changes or taking supplements so they can be tailored to your individual needs.
Medications and Treatments
While diet changes are the main way to manage FCS, exciting progress is being made: the FDA has approved a new medication, and more are in development to help lower triglyceride levels!
This progress is especially important for pancreatitis patients because severe hypertriglyceridemia is one of the leading preventable causes of acute pancreatitis. Until recently, treatment options were limited, often leaving patients vulnerable to repeated hospitalizations and life-threatening inflammation of the pancreas. These new drugs represent a turning point in prevention and long-term management.
Current Treatments
TRYNGOLZA (olezarsen)
Developed by Ionis Pharmaceuticals
TRYNGOLZA is the first medication approved by the FDA to treat adults with FCS.
ApoC-III is a protein made in the liver that slows down how the body clears fat (triglycerides) from the blood. TRYNGOLZA works by reducing the amount of apoC-III, helping the body clear triglycerides more efficiently. In clinical trials, patients using TRYNGOLZA alongside a FCS diet had lower triglycerides and fewer pancreatitis attacks.
This is a major breakthrough for people living with FCS, who previously had very limited options beyond strict dietary changes.
- TRYNGOLZA is given as a subcutaneous injection (under the skin), typically once a month.
Ionis is also investigating Olezarsen for the treatment of sHTG.
Learn more about TRYNGOLZA
Emerging Treatments
Developed by Arrowhead Pharmaceuticals
Plozasiran is an experimental drug currently being studied in clinical trials. It targets ApoC-III production to lower triglycerides.
On January 17, 2025, the FDA officially accepted Arrowhead’s New Drug Application (NDA) for Plozasiran, an exciting step toward potential approval. If approved, this would give patients with FCS another option to manage dangerously high triglyceride levels.
Clinical trials are ongoing to determine its safety and long-term effectiveness.
Multidisciplinary Care
Since FCS affects multiple aspects of health, a multidisciplinary team can provide comprehensive care necessary for the patient to understand and manage the disease effectively. This can include:
- Endocrinologist or Lipidologist: Specializes in lipid disorders and treatment options.
- Gastroenterologist: Helps manage pancreatitis and digestive complications.
- Dietitian: Guides appropriate dietary modifications and ensures proper nutrition.
- Primary Care Provider: Oversees overall health and coordinates care.
- Patient Support Groups: Offer education, emotional support, and advocacy resources.
Read more about the importance of a multidisciplinary care team.
Multifactorial Chylomicronemia Syndrome (MCS)
MCS is caused by a combination of genetic risk and secondary factors such as poor diet, uncontrolled diabetes, obesity, or alcohol use. It is more common than FCS and usually appears later in life. Unlike FCS, MCS is not caused by a single genetic mutation and typically responds to standard triglyceride-lowering medications.
Symptoms of Familial Chylomicronemia Syndrome:
People with FCS may experience:
Fluctuating abdominal discomfort
Extremely High Triglyceride Levels
Episodes of pancreatitis during triglyceride spikes
Nausea and bloating
Fatigue
Occasional xanthomas (small, yellowish bumps on the skin from fatty deposits)
Diagnosis of MCS
There is no single test that can confirm MCS. Instead, doctors often use a combination of test results, symptoms, and medical history to make a diagnosis.
Blood tests
Elevated triglyceride levels(often between 500–2,000 mg/dL)
Symptoms
Abdominal pain, nausea, episodes of pancreatitis, etc.
Genetic Testing
To rule out FCS
Medical and lifestyle history
- Any recent pancreatitis attacks
- Family history of high cholesterol or pancreatitis, other health conditions (like type 2 diabetes, thyroid disorders, or kidney disease)
- Medications that can raise triglycerides (like certain hormones or blood pressure medicines)
- Excessive alcohol use
MCS vs FCS
MCS and FCS can look very similar, so doctors may order genetic testing to help tell them apart.
- FCS is usually caused by a rare change in both copies of a gene that helps the body break down fat (called a homozygous mutation). This causes the genes to stop working, leading to very high triglyceride levels that don’t improve with diet or medication.
- MCS is more complex. People with MCS may have either:
- A single rare gene change (only one copy affected), or
- Many small, common gene differences that each have a tiny effect, but together, they raise triglyceride levels (this is called a polygenic mutation).
These changes don’t stop the genes from working completely, but they can make it harder to break down fat in the blood.
A big clue is how the body responds to treatment. If triglyceride levels improve with diet changes or medication, doctors are more likely to diagnose MCS.
Treatment of MCS
Treatment for MCS focuses on identifying and managing contributing factors alongside lowering triglycerides to reduce the risk of pancreatitis.
Treatment strategies may include:
Identifying and Managing Underlying Conditions and Factors
Diabetes, insulin resistance, certain medications, and excessive alcohol use can aggravate and increase triglycerides. Treatment will include managing underlying conditions. Any medications that cause sHTG should be discontinued if possible and replaced by alternatives that have less triglyceride-raising properties or used at as low a dose as possible.
Lifestyle Changes
- Avoiding alcohol
- Maintaining a healthy weight
- Both low-fat and low-carbohydrate diets have been investigated to decrease triglycerides in MCS patients.
Always consult a healthcare provider before making any dietary changes or taking supplements so they can be tailored to your individual needs.
Medications
While people with MCS often respond better to triglyceride-lowering medications than those with FCS, there’s still no single “cure.” Doctors may prescribe:
- Fibrates: reduce triglycerides
- Omega-3 fatty acids (prescription-strength): reduce triglycerides
- Statins: primarily for cholesterol, but sometimes used when triglycerides are also elevated
- Niacin: occasionally used, but less common due to side effects
While newer drugs like TRYNGOLZA are currently approved only for FCS, ongoing research may help expand treatment options for people with severe MCS in the future.
Secondary Hypertriglyceridemia
This form of sHTG is triggered by another health issue an individual is dealing with or certain medications they may be on. It may be temporary and improves when the root cause is treated.
| Dietary | Alcohol, sugars, starchy and refined carbs, and saturated and trans fats |
|---|---|
| Diseases | Chronic Kidney Disease (CKD) with or without Dialysis, Nephrotic syndrome, chronic liver disease, Cushing’s, HIV, Rheumatoid arthritis, Systemic Lupus Erythematosus (SLE), Lipodystrophy Lymphoma |
| Medications | Hormone-Related: Oral estrogens, tamoxifen, raloxifene, retinoids, glucocorticoids Immune-related: Cyclosporine, tacrolimus, sirolimus, cyclophosphamide, interferon Other: beta-blockers, thiazides, atypical antipsychotics, rosiglitazone, bile acid sequestrants, L-asparaginase |
| Metabolic Disorders | Obesity, insulin resistance and Diabetes, hypothyroidism, and 3rd trimester pregnancy |
Symptoms of Secondary sHTG
- Fatigue
- Nausea
- Vision changes
- Skin xanthomas (small, yellowish bumps on the skin caused by fatty deposits)
- Other symptoms related to the underlying condition
- Acute pancreatitis
Diagnosis of Secondary sHTG
- Elevated triglycerides on a blood test
- Identification of a secondary cause (reviewing medical history, medications, lab tests)
- Typically not genetic
Treatment of Secondary sHTG
Treatment for secondary sHTG focuses on identifying and addressing the underlying cause. In many cases, once the cause is treated or removed, triglyceride levels return to normal, sometimes without the need for long-term medication.
Identifying and Managing Underlying Conditions and Factors
Conditions like uncontrolled diabetes, insulin resistance, thyroid problems, certain medications, and excessive alcohol use can raise triglyceride levels. Treating these underlying issues is often the most effective step. In some cases, such as third-trimester pregnancy, triglyceride levels may return to normal after the condition resolves on its own.
Review Medications
Some drugs can raise triglycerides. If possible, doctors may:
- Lower the dose
- Switch to a different medication
- Stop the medication entirely
Lifestyle Changes
- Avoiding alcohol
- Maintaining a healthy weight
- Staying active
- Dietary Changes, especially avoiding simple carbohydrates and added sugars
- Medications (if needed)
Medications (if needed)
If triglyceride levels remain high after treating the cause and making lifestyle changes, doctors may prescribe fibrates, omega-3 fatty acids (prescription strength), statins or niacin, depending on individual risk factors.
Patient Resources & Support
Several organizations and programs offer support, education, and genetic testing for patients with Familial Chylomicronemia Syndrome
FCS Foundation
A nonprofit dedicated to supporting people with FCS through resources, education, and advocacy.
Free Genetic Testing Programs
- Ionis Pharmaceuticals: Know Your Triglycerides (7 genes)
- Arrowhead Pharmaceuticals: Genetic Testing Program (6 genes)
Frequently Asked Questions
There’s no single threshold for when high triglycerides cause acute pancreatitis. NCEP ATP III guidelines and Endocrine Society (2010) guidelines are frequently referred to by the medical community. Please note that different sources use different cut-offs:
- Some experts cite levels above 880 mg/dL as a pancreatitis risk threshold, particularly for people with FCS
- Others note that the risk increases significantly above 1000 mg/dL (5%), and becomes especially dangerous at 2000 mg/dL or more (10-20%).
- People who have had pancreatitis episodes in the past year are at a higher risk of developing acute pancreatitis at any triglyceride level compared to those who have not.
While there’s variability, it’s clear that the higher the triglycerides, the greater the risk, especially if left unmanaged.
Consult a healthcare provider to determine the root cause, as this can affect treatment options. Managing high triglycerides may involve dietary and lifestyle changes, medications if needed, and regular check-ups to ensure levels stay well-controlled.
Key Takeaways
- Triglycerides are fats in the blood that provide energy but, at high levels, can increase the risk of developing diseases like stroke, pancreatitis, heart disease, and others.
- Severe Hypertriglyceridemia (sHTG) (>880 mg/dL) can cause acute pancreatitis and other health issues.
- Familial Chylomicronemia Syndrome (FCS) is a rare genetic type of sHTG where the body cannot break down triglycerides.
- FCS symptoms include severe abdominal pain, pancreatitis, fatigue, brain fog, and fatty skin bumps (xanthomas) and diagnosis includes triglyceride testing, genetic testing, and ruling out secondary causes.
- FCS treatment focuses on a strict low-fat diet, working with a multidisciplinary care team, and using medications to lower triglyceride levels like the newly FDA-approved medication TRYNGOLZA.
- Other causes of sHTG include Multifactorial Chylomicronemia Syndrome (MCS) and secondary causes.
- Support organizations offer resources, genetic testing, and patient advocacy.
