What Is Carnosine?
Carnosine ($β$-alanyl-L-histidine) is a naturally occurring dipeptide found in high concentrations in muscle and brain tissue. It is composed of the amino acids beta-alanine and histidine. Carnosine levels tend to decline with age, and it is available as a dietary supplement, often derived from animal protein sources like beef, poultry, and fish. Its biological roles are multifaceted, primarily acting as a potent antioxidant, a glycation inhibitor, and a buffer of muscle pH. These properties have led to its exploration for various therapeutic applications, including supporting heart and brain health.
The Discrepancy: Animal Studies vs. Human Clinical Trials
Much of the initial excitement surrounding carnosine and its potential to lower cholesterol stemmed from encouraging results in animal models. Studies in rodents, particularly those with conditions like diabetes-associated atherosclerosis, have demonstrated positive effects on lipid profiles.
Animal Study Findings
- In diabetic and hyperlipidemic mice models, carnosine supplementation was found to significantly lower plasma triglyceride levels and block increases in cholesterol.
- Researchers observed a reduction in atherosclerotic lesion formation and prevented oxidation and glycation of low-density lipoprotein (LDL) cholesterol.
- One study in rats with high-fat diet-induced hyperlipidemia showed that a carnosine-based supplement improved total and LDL cholesterol levels, particularly in combination with simvastatin.
Human Clinical Trial Findings
However, replicating these lipid-lowering effects in human trials has proven difficult. A meta-analysis published in 2019, which reviewed long-term randomized controlled trials, found no significant effect of carnosine supplementation on total cholesterol (TC), LDL-C, or high-density lipoprotein cholesterol (HDL-C) levels. A more recent 14-week randomized controlled trial confirmed these findings, concluding that carnosine supplementation had no beneficial effects on lipid parameters in adults with prediabetes and type 2 diabetes who had well-controlled cardiovascular risk factors.
Key reasons for the difference between species
- Higher Carnosinase Activity in Humans: Humans have a high activity of the enzyme carnosinase 1 in their blood, which rapidly breaks down carnosine into its constituent amino acids. This means orally ingested carnosine has a very short half-life in human plasma, limiting its bioavailability. Rodents have much lower carnosinase activity, allowing carnosine to remain intact and exert its effects for longer periods.
- Different Disease Models: Animal studies often use models that create an aggressive disease state not perfectly comparable to human conditions. The effects observed in mice with advanced atherosclerosis may not translate directly to human populations with prediabetes or early-stage risk factors.
How Carnosine May Impact Cardiovascular Health Indirectly
Even if carnosine doesn't directly reduce standard cholesterol numbers, its other properties can still support cardiovascular health. The key is its protective effect on lipoproteins and blood vessels, rather than altering their concentration in the blood.
Antioxidant and Anti-Glycation Mechanisms
Carnosine's main benefit to the cardiovascular system is its ability to protect against oxidative stress and glycation, two processes that contribute to atherosclerosis, or the hardening of arteries.
- Prevents LDL Oxidation: Oxidized LDL ($ox$LDL) is a major contributor to plaque formation. Carnosine has been shown to prevent the oxidation of LDL by acting as a scavenger of reactive oxygen species (ROS). By inhibiting LDL oxidation, carnosine may help mitigate the development of atherosclerotic lesions.
- Inhibits Protein Glycation: Carnosine is an effective anti-glycating agent, reacting with reactive carbonyl species and preventing the formation of advanced glycation end products (AGEs). Glycation can damage proteins, including those on the surface of LDL particles, making them more prone to oxidation and uptake by macrophages, which form foam cells in arterial walls.
Clinical Research on Carnosine and Cholesterol
The following table summarizes key findings from recent human clinical trials and meta-analyses regarding carnosine and lipid profiles.
| Study / Meta-analysis | Participants | Duration | Key Lipid Findings | Conclusion on Cholesterol | Citation |
|---|---|---|---|---|---|
| de Courten et al. (2017) | 24 overweight/obese adults | 12 weeks | Maintained free cholesterol levels relative to placebo; no effect on total, HDL, or triglycerides | Did not lower standard cholesterol; noted beneficial effects on plasma lipidome | |
| Saadati et al. (2023) | 43 patients with prediabetes/T2DM | 14 weeks | No significant differences in total, LDL, or HDL cholesterol compared to placebo | No effect on lipid profile in well-controlled patients | |
| Al-Rasheedi & Al-Ghafri (2019) | 12-week trial, 85 pediatric patients | 12 weeks | Decreased total cholesterol, LDL-C, and triglycerides in intervention group | Reported positive lipid effects in specific patient group | * |
| Moradi et al. (2019) (Meta-analysis) | 4 RCTs (184 participants) | 12 weeks (Avg) | No significant change in total cholesterol, LDL, HDL, or triglycerides | Concluded carnosine has no effect on lipid parameters | |
| Petreski et al. (2020) (Meta-analysis) | 6 RCTs (401 participants) | Varied | Reported significantly lower total cholesterol and triglycerides, but high heterogeneity | Carnosine may improve some lipid profiles, needs more research |
*This study's positive findings contrast with other larger meta-analyses and more recent trials, highlighting the conflicting evidence and high heterogeneity in results.
Potential Cardiovascular and Safety Considerations
Beyond cholesterol, carnosine is associated with broader heart health benefits and considerations:
- Improved Exercise Performance in Heart Failure: One small study in patients with chronic heart failure found that carnosine supplementation improved exercise performance and quality of life.
- Protection Against Vascular Damage: The antioxidant and anti-glycation properties may protect vascular endothelium from damage, aiding in the prevention of plaque formation.
- Peripheral Vascular Disease: Carnosine may serve as an adjunct treatment for peripheral vascular disease due to its protective actions on the vascular endothelium.
- Interactions with Diabetes Medications: Carnosine may affect blood sugar levels, so patients taking anti-diabetes drugs should monitor their blood sugar closely.
- Pregnancy and Breastfeeding: There is insufficient reliable information on carnosine safety during pregnancy and breastfeeding, so it is best to avoid use.
Conclusion: Does Carnosine Lower Cholesterol?
While initial research in animal models showed promise for carnosine's ability to lower cholesterol and triglycerides, the translation of these effects to humans has been largely unsuccessful. Multiple human clinical trials and meta-analyses have concluded that carnosine supplementation does not significantly alter standard lipid profile parameters like total, LDL, and HDL cholesterol. The beneficial effects of carnosine on heart health are more likely attributed to its powerful antioxidant and anti-glycation properties, which protect lipoproteins from damage rather than changing their concentration in the blood. Therefore, carnosine should not be considered a primary treatment for hypercholesterolemia. Any individual considering carnosine supplementation should first consult a healthcare professional, especially if they have pre-existing health conditions or are taking other medications. For definitive lipid management, proven therapies and lifestyle changes are the recommended course of action.
This article is for informational purposes only and does not constitute medical advice. Consult a qualified healthcare provider for any health concerns or before starting a new supplement regimen.
Comparison of Carnosine's Lipid Effects
| Feature | Carnosine's Effect in Human Trials | Carnosine's Effect in Animal Studies | Significance for Cholesterol | Citation |
|---|---|---|---|---|
| Total Cholesterol | No significant reduction observed | Shown to decrease levels in some models | Does not directly lower total cholesterol in humans | |
| LDL Cholesterol | No significant reduction observed | Reduced in high-fat diet models | Ineffective for directly reducing LDL-C in humans | |
| HDL Cholesterol | No significant change | Increased in some rat studies | Does not directly increase HDL-C in humans | |
| LDL Oxidation | Protective effect via antioxidant action | Prevents oxidation and glycation of LDL | Key benefit; helps prevent atherosclerosis progression | |
| Triglycerides | Mixed results, some studies report no change, others suggest a decrease | Shown to significantly lower levels | Inconsistent human evidence; animal findings not replicated | |
| Free Cholesterol | Maintained levels relative to placebo in one small human study | Affected in some models | Suggests potential for affecting specific lipid species, but needs larger studies |
Conclusion
Based on the current weight of scientific evidence, carnosine is not an effective supplement for directly lowering cholesterol levels in humans. While animal studies and mechanistic research show promise for its effects on lipid metabolism and protection against lipoprotein damage, these benefits do not appear to translate to a significant reduction in standard total, LDL, or HDL cholesterol in human clinical trials. The robust antioxidant and anti-glycation properties of carnosine remain its primary mechanism for potentially benefiting cardiovascular health, but this should be viewed as a supportive, not primary, role. For individuals concerned about high cholesterol, standard medical treatments and dietary changes supported by strong clinical evidence are recommended. Consult with a healthcare provider to determine the best course of action for managing your cholesterol levels.
Key takeaways about carnosine and cholesterol
- Inconsistent Evidence: While animal studies often show carnosine can lower cholesterol, human trials have failed to consistently replicate these effects for total, LDL, or HDL cholesterol.
- Limited Bioavailability: The rapid breakdown of oral carnosine by the carnosinase enzyme in human blood may limit its ability to exert direct lipid-lowering effects.
- Indirect Heart Health Benefits: Carnosine's primary contribution to cardiovascular health likely comes from its antioxidant and anti-glycation properties, which protect against LDL oxidation and vascular damage.
- Not a Standalone Treatment: Carnosine should not be viewed as a primary therapy for high cholesterol and is not a substitute for standard lipid-lowering medications or lifestyle changes.
- Potential for Combination Therapy: One animal study suggested improved lipid outcomes when carnosine was combined with a statin, though human data is lacking.
- Consult Your Doctor: Individuals, especially those on diabetes or blood pressure medication, should consult a healthcare provider before starting carnosine supplementation.
FAQs
Q: Is carnosine an effective treatment for high cholesterol? A: No, current evidence from human clinical trials indicates that carnosine supplementation does not significantly lower total, LDL, or HDL cholesterol levels and should not be considered a treatment for high cholesterol.
Q: Why do animal studies show that carnosine lowers cholesterol but human studies don't? A: The primary reason is that humans have an enzyme called carnosinase 1 that rapidly breaks down carnosine in the blood, whereas rodents have very low levels of this enzyme. This difference in metabolism and bioavailability means carnosine remains in the body longer in animals, allowing it to exert its effects.
Q: What are the main cardiovascular benefits of carnosine? A: The main cardiovascular benefits of carnosine are related to its antioxidant and anti-glycation properties. It helps protect low-density lipoprotein (LDL) from oxidation and inhibits the formation of advanced glycation end products (AGEs), both of which are involved in the progression of atherosclerosis.
Q: Can carnosine help prevent heart disease? A: While carnosine's antioxidant and anti-glycation actions may support heart health by protecting against cellular damage, there is currently insufficient human evidence to conclude that it can prevent or treat cardiovascular disease.
Q: Are there any side effects associated with carnosine supplements? A: Carnosine is generally well-tolerated at typical dosages (e.g., 200-1500 mg daily). Potential side effects are rare, but it can affect blood sugar and blood pressure. Individuals should consult a doctor before supplementing, especially if pregnant, breastfeeding, or on medication.
Q: Does carnosine interact with statins or other medications? A: Carnosine may lower blood sugar, potentially interacting with diabetes medications. While one animal study showed combined benefit with a statin, more research is needed on human interactions. Always consult your doctor if you take medication.
Q: Should I take a carnosine supplement for my cholesterol? A: Based on available clinical evidence, carnosine is not recommended as a supplement for lowering cholesterol. You should follow proven strategies like a healthy diet, exercise, and medically prescribed therapies to manage your cholesterol levels effectively.
