InfoSynergy
Fish Oil
Fish Oil may add modest lipid-lowering effects to Fenofibrate for triglyceride lowering.
Recommendation: Use as part of the lipid plan, not as a substitute for prescribed therapy; recheck lipids after regimen changes.
Fenofibrate
Prescription ·Strong evidence ·Reviewed May 2026
Fenofibrate is an oral fibrate lipid-lowering agent used primarily to treat severe hypertriglyceridemia and mixed dyslipidemia. It substantially lowers triglycerides and modestly raises HDL cholesterol, and is often used as an adjunct to diet and, in selected patients, to statin therapy. Fenofibrate is a prodrug that is hydrolyzed to its active metabolite, fenofibric acid.
What it's good for
What to watch for
- Elevated liver enzymes (transaminases)
- Increased serum creatinine (usually reversible)
- Myalgia and muscle pain
- Severe renal impairment, including patients on dialysis3
- Active liver disease, including primary biliary cholangitis and unexplained persistent liver function abnormalities
The bottom line
Evidence rating strong. Most-documented uses: treatment of severe hypertriglyceridemia to reduce pancreatitis risk, management of primary hypercholesterolemia and mixed dyslipidemia, modest increase in hdl cholesterol. 4 sources indexed (2001–2019), with 5 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Fenofibrate is converted in vivo to fenofibric acid, which activates peroxisome proliferator-activated receptor alpha (PPAR-alpha). PPAR-alpha activation increases lipolysis and clearance of triglyceride-rich particles by inducing lipoprotein lipase and reducing apolipoprotein C-III, which normally inhibits lipoprotein lipase. It also stimulates hepatic fatty acid oxidation and increases synthesis of apolipoproteins A-I and A-II, contributing to higher HDL cholesterol. The net effect is a marked reduction in plasma triglycerides and VLDL, with smaller effects on LDL and HDL.4,1
Class
Fibrate (PPAR-alpha agonist)
Absorption
Water-soluble; take with food
Dosing
Dosing & protocol.
Common range
Fenofibrate 48 to 145 mg once daily (formulation-dependent; micronized and nanocrystallized products differ); fenofibric acid 35 to 135 mg once daily. Dose is reduced in renal impairment and the highest doses are avoided when eGFR is low.
Recommended form
Oral tablet or capsule once daily; bioavailability varies by formulation, so older non-micronized products are best taken with food while many newer micronized or nanocrystallized products may be taken without regard to meals.
Absorption is formulation-dependent. Older micronized and non-coated formulations are better absorbed with food, whereas certain nanocrystallized or coated products are designed to be taken without regard to meals. Follow the specific product labeling.
Depletions
What it depletes.
Nutrients this medication can lower over time, and what to replace.
Coenzyme Q10
MildFibrates inhibit HMG-CoA reductase activity indirectly and reduce mevalonate pathway flux similar to (though more weakly than) statins, lowering endogenous synthesis of ubiquinone (CoQ10), which shares this biosynthetic pathway. This effect is amplified when fenofibrate is combined with a statin, a common clinical scenario that also increases myopathy risk.
Replace Coenzyme Q10 (ubiquinone)Monitor Plasma/serum CoQ10 (rarely measured clinically); monitor for myalgia and serum creatine kinase if myopathy suspectedOnset Weeks to a few months of continuous therapy
Vitamin E
MildFenofibrate lowers circulating lipoproteins (VLDL and LDL) that transport fat-soluble vitamin E (tocopherols) in plasma. Because measured serum vitamin E is largely lipoprotein-bound, the marked triglyceride and lipoprotein reduction can lower total circulating vitamin E levels; true tissue depletion is less well established and the lipid-standardized vitamin E ratio may be unchanged.
Replace Vitamin E (mixed tocopherols) only if a documented deficiency is confirmedMonitor Serum alpha-tocopherol, ideally interpreted relative to serum lipids (tocopherol-to-cholesterol ratio)Onset Weeks to months, paralleling the lipid-lowering response
Safety
Full safety detail.
Side effects
- Elevated liver enzymes (transaminases)
- Increased serum creatinine (usually reversible)
- Myalgia and muscle pain
- Rare rhabdomyolysis, particularly with concurrent statin use
- Cholelithiasis (gallstones)
- Nausea, abdominal pain, and other gastrointestinal upset
- Headache
- Increased risk of venous thromboembolism
Contraindications
- Severe renal impairment, including patients on dialysis3
- Active liver disease, including primary biliary cholangitis and unexplained persistent liver function abnormalities
- Preexisting gallbladder disease
- Known hypersensitivity to fenofibrate or fenofibric acid4,1
- Breastfeeding
- Caution and dose adjustment with concurrent statin therapy due to increased myopathy and rhabdomyolysis risk
Interactions
Interaction records.
InfoSynergy
Berberine
Berberine may add modest lipid-lowering effects to Fenofibrate.
Recommendation: Use as part of the lipid plan, not as a substitute for prescribed therapy; recheck lipids after regimen changes.
InfoTiming Sensitive
Coenzyme Q10
Fibrates, like statins, may modestly lower endogenous coenzyme Q10 (ubiquinone) levels, and myopathy risk rises when fenofibrate is combined with a statin. CoQ10 supplementation is sometimes used to support patients with muscle symptoms, though evidence for symptomatic benefit is mixed. The two do not have a harmful pharmacokinetic interaction.
Recommendation: CoQ10 may be taken alongside fenofibrate, particularly if muscle aches occur on combined fibrate-statin therapy. It does not replace evaluation of unexplained muscle pain, weakness, or dark urine, which should prompt creatine kinase testing.
ModerateCaution
Milk Thistle
Fenofibrate can elevate liver transaminases and, rarely, cause hepatotoxicity. Milk thistle (silymarin) is taken for liver support but can mask or complicate interpretation of liver enzyme changes, and combining hepatically processed agents warrants attention to liver status rather than reliance on the supplement.
Recommendation: Do not use milk thistle as a substitute for monitoring fenofibrate-related liver effects. Continue scheduled liver function tests, and report fatigue, right-upper-quadrant pain, dark urine, or jaundice. Discuss any liver supplement use with the prescriber.
ModerateCaution
Garlic Extract
Fenofibrate has antiplatelet-like effects and is reported to potentiate the action of anticoagulants. Concentrated garlic extract has mild antiplatelet activity, so combining the two could additively increase bleeding tendency, particularly in patients also taking warfarin, antiplatelet drugs, or other blood-thinning supplements.
Recommendation: Use concentrated garlic supplements cautiously with fenofibrate, especially around surgery or alongside anticoagulant/antiplatelet therapy. Watch for easy bruising, nosebleeds, or prolonged bleeding, and inform clinicians of supplement use.
Sources
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Randomized controlled trials
2- 1Effects of combination lipid therapy in type 2 diabetes mellitus (ACCORD Lipid)Needs reviewPMIDGinsberg HN, Elam MB, Lovato LC, et al. · New England Journal of Medicine · 2010
Adding fenofibrate to simvastatin did not reduce cardiovascular events overall, though a possible benefit was seen in patients with high triglycerides and low HDL.
- 2Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study)Needs reviewPMIDKeech A, Simes RJ, Barter P, et al. · Lancet · 2005
Fenofibrate lowered triglycerides and reduced nonfatal myocardial infarction, though it did not significantly reduce the primary coronary endpoint in the overall diabetic population.
Reviews & position papers
1- 3Fenofibrate, homocysteine and renal functionNeeds reviewNo linkWestphal S, Dierkes J, Luley C · Cardiovascular Drugs and Therapy · 2001
Fenofibrate raises plasma homocysteine in some analyses while it has been associated with reversible elevations in serum creatinine, complicating interpretation of renal effects.
Reference material
1- 4TriCor (fenofibrate) tablets prescribing informationNeeds reviewNo linkAbbVie Inc. · US FDA Prescribing Information · 2019
Fenofibric acid activates PPAR-alpha, increasing lipolysis and clearance of triglyceride-rich particles and modestly raising HDL.
Keep exploring
Deep dives & adjacent profiles.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Fenofibrate in NutriStack.
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