The increasingly widespread use of herbal and other forms of alternative medicine has stimulated research into their purported effects on human health. A recent meta-analysis in Nutrients examined recent studies on the cornelian cherry, Cornus mas L., for evidence of its cardiometabolic benefit.
Cardiometabolic disease
Noncommunicable diseases (NCD) claim the lives of 17 million people under 70 years annually, with cardiometabolic disease making up a major chunk. By 2030, 77% of the disease burden will be due to NCDs.
Cardiometabolic diseases comprise illnesses due to both cardiovascular and metabolic factors. Examples include cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM) and the metabolic syndrome.
These share the same risk factors, namely, dyslipidemia, impaired blood glucose control, hypertension, visceral or abdominal obesity, and raised liver enzymes. They operate via the same pathways to produce a spectrum of related outcomes.
Raised liver enzymes (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) are also markers, not of impaired liver function as in non-alcoholic fatty liver disease (NAFLD). as was long thought, but of developing type 2 diabetes mellitus (T2DM). They are also associated with cardiovascular disease (CVD) risk factors.
A high prevalence of smoking, sedentary lifestyles, and more unhealthy dietary patterns predispose to an increased incidence and prevalence of cardiometabolic disease. An active lifestyle and dietary modifications are key to reversing this trend.
Bioactivity of cornelian cherry
Cornelian cherries have been part of traditional medicine for over a thousand years in much of central Asia and Eastern Europe, up to Iran. They are used to treat a variety of issues, including sore throat, poor digestion, liver and kidney disease, and some infections like measles or chickenpox.
The cornelian cherry contains an abundance of bioactive compounds, predominantly anthocyanins, and iridoids like organic acid. These compounds have anti-inflammatory, anti-diabetic, and, therefore, cardioprotective and liver-protective benefits, in addition to lowering blood cholesterol levels.
Anthocyanins increase NO release from the endothelium, inhibit vasoconstrictor levels, and cause vasodilation.
Anthocyanins activate adenosine monophosphate (AMP)-activated kinase (AMPK) that inhibits cholesterol and triglyceride synthesis. This reduces LDL and HDL cholesterol levels.
Iridoids reduce serum lipid levels and prevent atheromatous changes. A 44% reduction in triglycerides was reported in a hypercholesterolemic rabbit study after 60 days of cornelian cherry supplementation.
Animal studies indicated improved glycemic control following supplementation with anthocyanins, ursolic acid, cornelian cherry, or its extract. Anthocyanins improve insulin sensitivity and suppress the breakdown of complex carbohydrates into digestible simple sugars.
Ursolic acid acts via multiple pathways to restore insulin sensitivity, improve glycogen levels, and stimulate glucose uptake by muscle cells, resolving the metabolic syndrome. Loganic acid also increases antioxidant activity with reduced formation of glycation and oxidation products.
Evidence for the cardiometabolic benefits of Cornelian cherry supplementation or therapy is still needed to develop concentrated commercial formulations for convenient use.
Promising animal and herbal medicine trial results led to human randomized controlled trials (RCTs). The current study aimed to evaluate the effects of cornelian cherry using data from several RCTs with cardiometabolic outcome parameters.
About the study
The six RCTs included here involved the use of cornelian cherry in fruit, powder, and extract form in adults. The outcomes measured included cardiovascular endpoints, anthropometric measures, and metabolic parameters that respond to lifestyle modification.
Three of the studies included people with metabolic-dysfunction-associated fatty liver disease (MAFLD). One included people with T2DM, one those with insulin resistance, and one comprised postmenopausal women.
Cornelian cherry dosage ranged from 500mg per day to 20 mL per day or 20-30 g per day of dried powder. The study periods extended from six to twelve weeks.
Outcomes evaluated included triglycerides (TG), total cholesterol (TC), LDL, HDL, fasting blood glucose (FBG), insulin, glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR), AST/ALT, body weight, body mass index (BMI), and waist circumference (WC).
What did the study show?
The results suggest “a favorable impact of cornelian cherry supplementation on anthropometric measurements, lipid profile, and glycemic parameters.”
Overall, there was a significant drop in body weight with a standardized mean difference (SMD) of -0.27. The BMI also dropped with an SMD of -0.42. Despite this, waist circumference (WC) did not change after adjusting for inter-study heterogeneity.
Glycemic control improved, with FBG falling (SMD of -0.46). Glycated HbA1c, which indicates the mean level of blood glucose over the last 120 days, decreased, with the SMD being -0.70. Insulin levels registered no change.
High-density lipoprotein (HDL) cholesterol went up (SMD of 0.38) without changes in total plasma triglycerides and total and low-density lipoprotein (LDL) cholesterol. Liver size or function also failed to show any effect post-intervention.
Only one study on 50 MAFLD cases measured blood pressure. Both systolic and diastolic blood pressure were reduced by -9 mm Hg each.
Conclusions
“Supplementation with cornelian cherry may impact diverse cardiometabolic risk factors among individuals considered to be at a high risk.” While multiple studies corroborate the findings of this paper, others contradict them. This could be due to differing study durations, different formulations, and anthocyanin content.
For instance, a previous meta-analysis suggested that cornelian cherry reduced triglyceride and LDL levels. However, it was based on a dose of 300 mg/day or more, vs. 30-150 mg/day for the studies covered in this paper, perhaps accounting for the variation in results.
The authors suggest supplementation with at least 300 mg anthocyanins and 20mg/kg body weight of iridoids.
Existing literature indicates positive effects on liver function with cornelian cherry in animals but not in humans, suggesting poor activity with liver disease.
Further studies should explore whether cornelian cherry independently induces weight loss as well as indirectly via weight loss. Larger studies, with standardized dosages and durations and high internal validity, are required for more reliable and reproducible results.
Considering the benefits and acceptability of dietary therapy vs. drugs over the long term, there must be evidence of actual improvement in disease endpoints with supplementation rather than merely altering biomarker levels.