Lipid profile could be modified by Mediterranean diet (MD) and by red yeast rice (RYR). We assessed the lipid-lowering effects of MD alone or in combination with RYR on dyslipidemic statin-intolerant subjects, with or without type 2 diabetes, for 24 weeks. We evaluated the low-density lipoprotein (LDL) cholesterol level, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride, liver enzyme, and creatinine phosphokinase (CPK) levels. We studied 171 patients: 46 type 2 diabetic patients treated with MD alone (Group 1), 44 type 2 diabetic patients treated with MD associated with RYR (Group 2), 38 dyslipidemic patients treated with MD alone (Group 3), and 43 dyslipidemic patients treated with MD plus RYR (Group 4). The mean percentage changes in LDL cholesterol from the baseline were
The prevalence of metabolic syndromes (MS) and the associated cardiovascular diseases (CVDs) is increasing rapidly around the world. Lifestyle measures, including dietary changes and physical activity, play a crucial role in preventing these conditions, and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) has already suggested dietary intervention to contain this epidemic [
Cardiovascular risk factors in MS could be modified by dietary interventions. The Mediterranean diet (MD) is characterized by a high consumption of monounsaturated fatty acids (primarily from olive oil) and a daily consumption of fruit, vegetables, whole-grain cereals, and low-fat dairy products; weekly consumption of fish, poultry, tree nuts, and legumes; a relatively low consumption of red meats (approximately twice a month) [
Some studies have shown that red yeast rice (RYR) reduces low-density lipoprotein (LDL) cholesterol levels in hypercholesterolemic patients [
A combination of RYR extract, policosanol, berberine, folic acid, and Q10 coenzyme reportedly induced a significant metabolic improvement in elderly patients with dyslipidemia [
In nondiabetic patients with dyslipidemia, a combination of RYR, policosanol, berberine, folic acid, and Q10 coenzyme in addition to dietary counseling was found to amplify the effect of diet on central obesity, improve lipid profiles and blood pressure, and reduce the incidence of MS [
To our knowledge, little is known about the efficacy of RYR extract in patients with type 2 diabetes. In particular, no data are available on the effect of RYR supplementation combined with a Mediterranean diet on the lipid profiles of such patients. Hence, this randomized, parallel-group controlled study lasting six months to investigate whether adding a combination of RYR extract, artichoke extract, resveratrol, chrome, folic acid, and coenzyme Q10 (Redulip, For Farma srl) to the Mediterranean diet could improve the lipid profile of dyslipidemic patients with and without type 2 diabetes.
This study was designed as a controlled, randomized, parallel-group study and complied with the content of the Helsinki Declaration. The Local Institutional Review Board approved the study protocol and all participants provided written informed consent.
We studied consecutive patients attending our outpatient clinic from January to October 2010. Patients were included in the study if they had total cholesterol levels higher than 200 mg/dL and/or low-density lipoprotein (LDL) cholesterol levels higher than 130 mg/dL and a cardiovascular risk (as assessed according to the Progetto Cuore) of ≤10% for dyslipidemic patients and ≤15% for diabetic patients [
The sample of 171 eligible participants included 90 type 2 diabetic patients with dyslipidemia and 81 dyslipidemic patients without type 2 diabetes.
At the baseline visit, we used 24-hour recall, a self-reporting method for collecting data on eating behavior and measuring energy intake by means of structured interviews, as described elsewhere [
The primary outcome was the low-density lipoprotein (LDL) cholesterol level measured at the baseline and after 24 weeks. Secondary outcomes included total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride, liver enzyme, and creatinine phosphokinase (CPK) levels.
Patients attended follow-up visits after 24 weeks of treatment. None of the patients dropped out of the study.
At each visit, all patients were assessed in terms of body mass index (BMI), diastolic and systolic blood pressure (measured with patients being seated, using a standard sphygmomanometer), and waist circumference (midway between the lowest rib and the iliac crest).
A fasting blood sample was obtained at the baseline and at week 24 to measure LDL cholesterol, TC, HDL cholesterol, triglyceride, CPK, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. All analyses were performed at the laboratory of the University Hospital of Padua, Italy.
At weeks 24, patients’ dietary compliance was assessed using the 24-hour recall method [
Values are expressed as mean ± SD or SEM. Data were normalized according to each patient’s baseline situation by calculating the difference (after-before) at the two follow-up times considered (24 weeks after starting the study) and expressing the value as a percentage of the parameters at the baseline. Negative values therefore indicate the effective percentage decrease in the parameter following the treatment. ANOVA followed by the
Table
Baseline anthropometric and haematochemical parameters in the four groups of patients. Data are the mean
Group 1 |
Group 2 |
Group 3 |
Group 4 |
| ||
---|---|---|---|---|---|---|
Group 1 versus 2 | Group 3 versus 4 | |||||
Gender (M/F) | 19/27 | 18/26 | 20/18 | 14/29 | n.s. | n.s. |
Age (yrs) |
|
|
|
|
n.s | n.s. |
Height (m) |
|
|
|
|
n.s. | n.s. |
Body weight (kg) |
|
|
|
|
n.s. | ● |
BMI |
|
|
|
|
● | ●● |
Waist (cm) |
|
|
|
|
n.s | ●● |
TC (mg/dL) |
|
|
|
|
n.s. | ●●● |
LDL (mg/dL) |
|
|
|
|
n.s. | ●●● |
HDL (mg/dL) |
|
|
|
|
n.s. | ●●● |
TG (mg/dL) |
|
|
|
|
n.s. | ● |
CPK (ng/mL) |
|
|
|
|
n.s | n.s. |
AST (mU/mL) |
|
|
|
|
n.s | n.s. |
ALT (mU/mL) |
|
|
|
|
n.s | ●● |
GGT (mU/mL) |
|
|
|
|
n.s | n.s. |
Systolic BP (mmHg) |
|
|
|
|
●● | n.s. |
Diastolic BP (mmHg) |
|
|
|
|
● | n.s. |
To assess statistical differences between groups, ANOVA followed by
●●●:
Abbreviations: BMI: body mass index; TC: total cholesterol; LDL: low-density lipoprotein; HDL: high-density lipoprotein; TG: triglyceride; CPK: creatinine phosphokinase; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: gamma glutamyl transferase; BP: blood pressure.
Table
Differences (
Difference (after − before) |
Group 1 |
Group 2 |
Group 3 |
Group 4 |
| |||||
---|---|---|---|---|---|---|---|---|---|---|
Group 1 versus 2 | Group 3 versus 4 | |||||||||
|
0.89 |
|
−0.86 |
|
−3.89 |
|
−0.87 |
|
n.s. | ●● |
|
0.89 |
|
−0.86 |
|
−3.89 |
|
−0.87 |
|
n.s. | ●● |
|
−0.89 |
|
−0.93 |
|
−2.42 |
|
−0.98 |
|
n.s. | n.s. |
|
−4.65 |
|
−15.45 |
|
−11.96 |
|
−16.94 |
|
●●● | ● |
|
−7.34 |
|
−21.02 |
|
−12.47 |
|
−22.00 |
|
●●● | ●● |
|
2.87 |
|
−2.93 |
|
−0.11 |
|
−1.94 |
|
● | n.s. |
|
2.30 |
|
−3.77 |
|
−7.24 |
|
−7.52 |
|
n.s. | n.s. |
|
−2.84 |
|
−3.51 |
|
−1.15 |
|
2.14 |
|
n.s. | n.s. |
|
−6.48 |
|
−7.52 |
|
0.52 |
|
−0.78 |
|
n.s. | n.s. |
|
−6.60 |
|
−7.12 |
|
−12.37 |
|
1.60 |
|
n.s. | ● |
|
8.47 |
|
10.30 |
|
−6.89 |
|
−1.48 |
|
n.s | n.s. |
|
3.42 |
|
−2.06 |
|
−0.47 |
|
1.51 |
|
● | n.s. |
|
3.03 |
|
−0.41 |
|
−0.23 |
|
0.49 |
|
n.s. | n.s. |
Statistical significance for difference (after − before); treatment within each group of patients was checked with Student’s
To assess statistical differences between groups, ANOVA followed by
Abbreviations: BMI: body mass index; TC: total cholesterol; LDL: low-density lipoprotein; HDL: high-density lipoprotein; TG: triglyceride; CPK: creatinine phosphokinase; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: gamma glutamyl transferase; BP: blood pressure.
Data are the mean
Table
A significant drop in TC was seen in all groups of patients. In particular, the average reduction in TC 24 weeks after the baseline was
The mean percentage changes in LDL cholesterol levels from the baseline were
We found no significant differences in terms of HDL cholesterol and triglycerides levels in any of the groups (Table
Regarding the safety of treatment with NCP, there was no significant increase in CPK or liver-associated enzyme levels in any of the patients after 24 weeks of treatment. None of the patients discontinued the treatment with NCP and no side effects were observed. As regards liver function, we observed after 24 weeks of treatment a significant drop in AST and ALT levels in type 2 diabetic patients (Groups 1 and 2) from the baseline. In particular, we observed in Group 1 a decline in AST levels of
This controlled, randomized, parallel-group study demonstrated that, in statin-intolerant patients, associating a MD with a combination of nutraceuticals (NUTs) based on red yeast rice extract can significantly improve dyslipidemic patients’ lipid profiles by comparison with diet alone.
The effects of MD on lipid profile and in protecting against cardiovascular risks are well known.
In a recent meta-analysis, MD was also found associated with a lower risk of MS; in particular, several studies showed the beneficial role of MD on HDL cholesterol and triglyceride levels [
In agreement with previous studies, our findings showed that adherence to MD alone significantly reduced BMI, waist circumference, TC, and LDL cholesterol levels in overweight dyslipidemic patients without type 2 diabetes. The beneficial effects of MD on BMI and waist circumference were not seen in type 2 diabetic patients. These findings are consistent with other reports of weight loss programs proving less effective in overweight and obese diabetic patients [
Our results also indicate that associating a combination of NUTs with MD can add to the lipid-lowering effect of MD, in particular on LDL cholesterol, in terms of a 10% improvement in dyslipidemic patients.
A previous study demonstrated the effect of a combination of red yeast rice extract and berberine (an isoquinoline alkaloid found in plants of the genus
Associating a combination of NUTs with a Mediterranean-style diet could prove a valuable therapeutic option for dyslipidemic statin-intolerant patients at low cardiovascular risk without excessively high LDL cholesterol levels.
The composition of the NUTs used in some previous studies varied considerably, particularly in terms of the concentration of monacolin K, which ranged from 9.6 mg to 3 mg. The dose of monacolin K in the NUTs used in our study was 3 mg. Becker et al. [
We recorded none of the adverse effects described elsewhere in patients treated with red yeast rice [
To our knowledge, ours is the first study to show that associating MD with NUTs can improve, in terms of 21%, LDL cholesterol levels of type 2 diabetic statin-intolerant patients. It is often difficult to obtain a normalization of TC, or even of LDL cholesterol, with dietary restrictions alone in diabetic patients, so adding a NUT based on red yeast rice might be a good therapeutic option for type 2 diabetic patients, at low cardiovascular risk with no evidence of vascular damage or other complications, who have previous statin intolerance. The reduction in LDL cholesterol levels achieved with MD plus NUTs was similar to the reduction obtained using statins, as already reported in dyslipidemic patients with statin intolerance [
The limitation of this study is the small size of the sample studied; further studies on larger samples will be needed to confirm the validity of this patient management approach, particularly in cases of type 2 diabetes.
Despite its limitations, this study provides useful new insight into the nutraceutical/dietary treatment of lipid profiles, even in patients with type 2 diabetes. Our results indicate that MD counseling alone is effective in reducing LDL cholesterol levels in moderately hypercholesterolemic patients with a presumably low cardiovascular risk, but associating MD with the administration of RYR improved patients’ lipid profiles considerably more, also in patients with type 2 diabetes with statin intolerance.