Effectiveness and safety of red yeast rice predominated by monacolin K β-hydroxy acid form for hyperlipidemia treatment and management

doi:10.19852/j.cnki.jtcm.2022.02.007

Abstract

Abstract:

OBJECTIVE: To assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K β-hydroxy acid form (MKA), Heye (Folium Nelumbinis), and Cangzhu (Rhizoma Atractylodis Lanceae), compared to lifestyle modifications.

METHODS: Totally 117 subjects with moderate to severe dyslipidemia (according to Chinese guidelines) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of MKA, LM plus a high dosage of MKA, and treated for 60 d. The primary endpoint was the reduction of low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Safeties along with Traditional Chinese Medicine Syndromes were assessed through the study.

RESULTS: A low dosage of MKA along with lifestyle modifications caused a significant decrease in LDL-C by 15.6% on average (95% CI, 9.6% to 21%) with, a decrease in TC by 15.3% on average (95% CI, 9.26% to 21.4%), and a decrease in non-HDL-C by 35.4% (95% CI, 25.76% to 41.34%). Weak evidence of a reduction of triglycerides but an increment of HDL-C was observed in patients with severe hyperlipidemia. No severe adverse events occurred during the study.

CONCLUSION: Our results confirm the LDL-C and TC lowering properties of MKA is clinically meaningful. It also produces a significant reduction of non-HDL-C, and slightly effects on TG and HDL-C as well.

Key words: hydroxy acids, lovastatin, hyperlipidemias, cholesterol, cardiovascular prevention, lifestyle modifications, red yeast rice

CHEN Benjian, HUANG Xiaodan, PENG Huiting, LI Yishi, CAO Yongtao, WU Huanlin, XU Danping. Effectiveness and safety of red yeast rice predominated by monacolin K β-hydroxy acid form for hyperlipidemia treatment and management[J]. Journal of Traditional Chinese Medicine, 2022, 42(2): 264-271.

Figures/Tables 6

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Variable	MKA-high (n = 37)	MKA-low (n = 35)	LM (n = 39)	^aP value
Age (years)	59.60±10.60	57.80±10.60	61.40±11.90	0.39
Gender female [n (%)]	27 (71.0)	25 (71.4)	25 (64.1)	0.74
Body weight (kg)	59.80±10.20	61.70±11.10	60.80±9.73	0.74
Body mass index (kg/m²)	24.10±3.30	24.20±3.28	23.60±2.89	0.62
LDL-C (mmol/L)	4.12±1.01	4.17±0.72	4.24±0.75	0.81
TC (mmol/L)	6.13±0.93	5.94±0.81	6.04±0.77	0.62
HDL-C (mmol/L)	1.38±0.51	1.32±0.32	1.33±0.32	0.73
Triglycerides (mmol/L)	2.24±1.62	1.82±0.71	1.56±0.87	0.035
Non-HDL-C (mmol/L)	4.75±0.98	4.62±0.76	4.71±0.83	0.82
Apo-A1 (g/L)	1.43±0.29	1.45±0.21	1.38±0.23	0.43
Apo-B (g/L)	1.38±0.29	1.36±0.21	1.37±0.27	0.97
LP(a) (mg/L)	233.00±304.00	214.00±262.00	208.00±154.00	0.90
ALT (U/L)	19.80±9.05	20.60±13.50	28.00±40.20	0.30
AST (U/L)	19.40±4.91	20.50±8.49	27.80±25.60	0.048
BUN (mmol/L)	4.78±1.05	5.14±0.92	5.49±2.19	0.13
Scr (μmol/L)	71.70±20.00	74.00±3.30	75.00±21.20	0.73
UA (μmol/L)	364.00±112.00	386.00±88.00	376.00±79.90	0.61
Creatine kinase (U/L)	122.00±83.90	109.00±48.90	74.80±41.80	0.003
Creatine kinase-MB (U/L)	15.00±3.92	17.50±11.50	17.80±17.40	0.56
Lactic dehydrogenase (U/L)	188.00±29.40	188.00±40.70	214.00±67.90	0.028
Glucose (mmol/L)	6.10±1.69	5.60±0.70	5.43±1.30	0.08
Red blood cell (10¹²/L)	4.72±0.44	4.89±0.70	4.20±0.74	< 0.001
Hemoglobin (g/L)	136.00±11.90	137.00±12.00	121.00±18.50	< 0.001
White blood cell (10⁹/L)	6.38±1.38	6.75±1.66	6.55±2.32	0.69
Platelet (10⁹/L)	246.00±57.50	263.00±67.10	234.00±87.70	0.22
Dizziness [n (%)]	15 (39.5)	8 (22.9)	11 (28.2)	0.29
Chest distress [n (%)]	14 (36.8)	10 (28.6)	13 (33.3)	0.75
Head heavy [n (%)]	12 (31.6)	9 (25.7)	10 (25.6)	0.80
Fatigue [n (%)]	16 (42.1)	13 (37.1)	16 (41)	0.9
Heavy limbs [n (%)]	22 (57.9)	17 (48.6)	21 (53.8)	0.73
Vomiting/phlegm [n (%)]	12 (31.6)	3 (8.6)	15 (38.5)	0.01
Bloating [n (%)]	18 (47.4)	14 (40)	13 (25.6)	0.45
Taste changes [n (%)]	9 (23.7)	4 (11.4)	5 (12.8)	0.29
Syrigmus [n (%)]	14 (36.8)	12 (34.3)	8 (20.5)	0.25
Reduced appetite [n (%)]	5 (13.2)	2 (5.7)	12 (30.8)	0.01
Ventosity [n (%)]	13 (34.2)	8 (22.9)	15 (38.5)	0.34
Lower limb edema [n (%)]	7 (18.4)	9 (25.7)	8 (20.5)	0.74
Loose stools [n (%)]	14 (36.8)	12 (34.3)	12 (30.8)	0.85

Variable	MKA-high (n = 37)	MKA-low (n = 35)	LM (n = 39)	^aP value
Age (years)	59.60±10.60	57.80±10.60	61.40±11.90	0.39
Gender female [n (%)]	27 (71.0)	25 (71.4)	25 (64.1)	0.74
Body weight (kg)	59.80±10.20	61.70±11.10	60.80±9.73	0.74
Body mass index (kg/m²)	24.10±3.30	24.20±3.28	23.60±2.89	0.62
LDL-C (mmol/L)	4.12±1.01	4.17±0.72	4.24±0.75	0.81
TC (mmol/L)	6.13±0.93	5.94±0.81	6.04±0.77	0.62
HDL-C (mmol/L)	1.38±0.51	1.32±0.32	1.33±0.32	0.73
Triglycerides (mmol/L)	2.24±1.62	1.82±0.71	1.56±0.87	0.035
Non-HDL-C (mmol/L)	4.75±0.98	4.62±0.76	4.71±0.83	0.82
Apo-A1 (g/L)	1.43±0.29	1.45±0.21	1.38±0.23	0.43
Apo-B (g/L)	1.38±0.29	1.36±0.21	1.37±0.27	0.97
LP(a) (mg/L)	233.00±304.00	214.00±262.00	208.00±154.00	0.90
ALT (U/L)	19.80±9.05	20.60±13.50	28.00±40.20	0.30
AST (U/L)	19.40±4.91	20.50±8.49	27.80±25.60	0.048
BUN (mmol/L)	4.78±1.05	5.14±0.92	5.49±2.19	0.13
Scr (μmol/L)	71.70±20.00	74.00±3.30	75.00±21.20	0.73
UA (μmol/L)	364.00±112.00	386.00±88.00	376.00±79.90	0.61
Creatine kinase (U/L)	122.00±83.90	109.00±48.90	74.80±41.80	0.003
Creatine kinase-MB (U/L)	15.00±3.92	17.50±11.50	17.80±17.40	0.56
Lactic dehydrogenase (U/L)	188.00±29.40	188.00±40.70	214.00±67.90	0.028
Glucose (mmol/L)	6.10±1.69	5.60±0.70	5.43±1.30	0.08
Red blood cell (10¹²/L)	4.72±0.44	4.89±0.70	4.20±0.74	< 0.001
Hemoglobin (g/L)	136.00±11.90	137.00±12.00	121.00±18.50	< 0.001
White blood cell (10⁹/L)	6.38±1.38	6.75±1.66	6.55±2.32	0.69
Platelet (10⁹/L)	246.00±57.50	263.00±67.10	234.00±87.70	0.22
Dizziness [n (%)]	15 (39.5)	8 (22.9)	11 (28.2)	0.29
Chest distress [n (%)]	14 (36.8)	10 (28.6)	13 (33.3)	0.75
Head heavy [n (%)]	12 (31.6)	9 (25.7)	10 (25.6)	0.80
Fatigue [n (%)]	16 (42.1)	13 (37.1)	16 (41)	0.9
Heavy limbs [n (%)]	22 (57.9)	17 (48.6)	21 (53.8)	0.73
Vomiting/phlegm [n (%)]	12 (31.6)	3 (8.6)	15 (38.5)	0.01
Bloating [n (%)]	18 (47.4)	14 (40)	13 (25.6)	0.45
Taste changes [n (%)]	9 (23.7)	4 (11.4)	5 (12.8)	0.29
Syrigmus [n (%)]	14 (36.8)	12 (34.3)	8 (20.5)	0.25
Reduced appetite [n (%)]	5 (13.2)	2 (5.7)	12 (30.8)	0.01
Ventosity [n (%)]	13 (34.2)	8 (22.9)	15 (38.5)	0.34
Lower limb edema [n (%)]	7 (18.4)	9 (25.7)	8 (20.5)	0.74
Loose stools [n (%)]	14 (36.8)	12 (34.3)	12 (30.8)	0.85

Variable	MAK-High (n = 37)												^dP value
Variable	Baseline		Day 60	^aP value	Baseline		Day 60	^bP value		Baseline	Day 60	^cP value	^dP value
LDL-C (mmol/L)	4.12±1.01		3.48±1.28	< 0.001		4.17±0.72	3.52±0.74	< 0.001	4.24±0.75		4.16±0.83	0.53	0.004
TC (mmol/L)	6.13±0.93		5.59±0.99	< 0.001		5.94±0.81	5.03±1.06	< 0.001	6.04±0.77		5.86±0.82	0.17	0.002
HDL-C (mmol/L)	1.38±0.51		1.36±0.47	0.72		1.32±0.32	1.33±0.31	0.62	1.33±0.32		1.26±0.34	0.15	0.32
Triglycerides (mmol/L)		2.24±1.62	2.58±3.17	0.37		1.82±0.71	1.66±0.82	0.08	1.56±0.87		1.65±1.07	0.43	0.31
Non-HDL-C (mmol/L)		4.75±0.98	4.23±1.16	< 0.001		4.62±0.76	3.07±1.03	< 0.001	4.71±0.83		3.50±1.06	< 0.001	< 0.001
Apo-Al (g/L)	1.43±0.29		1.50±0.28	0.008		1.45±0.21	1.78±2.07	0.37	1.38±0.23		1.36±0.29	0.67	0.45
Apo-B (g/L)	1.38±0.29		1.23±0.33	< 0.001		1.36±0.21	3.71±15.00	0.36	1.37±0.27		1.32±0.29	0.2	0.37
LP (a) (mg/L)	233.00±304.00		252.00±327.00	0.58		214.00±262.00	208.00±275.00	0.64	208.00±154.00		215.00±167.00	0.66	0.76

Variable	MAK-High (n = 37)												^dP value
Variable	Baseline		Day 60	^aP value	Baseline		Day 60	^bP value		Baseline	Day 60	^cP value	^dP value
LDL-C (mmol/L)	4.12±1.01		3.48±1.28	< 0.001		4.17±0.72	3.52±0.74	< 0.001	4.24±0.75		4.16±0.83	0.53	0.004
TC (mmol/L)	6.13±0.93		5.59±0.99	< 0.001		5.94±0.81	5.03±1.06	< 0.001	6.04±0.77		5.86±0.82	0.17	0.002
HDL-C (mmol/L)	1.38±0.51		1.36±0.47	0.72		1.32±0.32	1.33±0.31	0.62	1.33±0.32		1.26±0.34	0.15	0.32
Triglycerides (mmol/L)		2.24±1.62	2.58±3.17	0.37		1.82±0.71	1.66±0.82	0.08	1.56±0.87		1.65±1.07	0.43	0.31
Non-HDL-C (mmol/L)		4.75±0.98	4.23±1.16	< 0.001		4.62±0.76	3.07±1.03	< 0.001	4.71±0.83		3.50±1.06	< 0.001	< 0.001
Apo-Al (g/L)	1.43±0.29		1.50±0.28	0.008		1.45±0.21	1.78±2.07	0.37	1.38±0.23		1.36±0.29	0.67	0.45
Apo-B (g/L)	1.38±0.29		1.23±0.33	< 0.001		1.36±0.21	3.71±15.00	0.36	1.37±0.27		1.32±0.29	0.2	0.37
LP (a) (mg/L)	233.00±304.00		252.00±327.00	0.58		214.00±262.00	208.00±275.00	0.64	208.00±154.00		215.00±167.00	0.66	0.76

Variable	MKA-high (n = 37)			MKA-low (n = 35)						LM (n = 39)						^dP value
Variable	Baseline	Day 60	^aP value		Baseline		Day 60		^bP value		Baseline		Day s60		^cP value	^dP value
Dizziness [n (%)]	0.395±0.079	0.263±0.071	0.2668	0.229±0.070		0.029±0.028		0.0156		0.282±0.072		0.308±0.074		1.000		0.04
Chest distress [n (%)]	0.368±0.078	0.290±0.073	0.6072	0.286±0.076		0.200±0.068		0.5078		0.333±0.075		0.308±0.074		1.000		0.83
Heavy Head [n (%)]	0.316±0.075	0.226±0.068	0.1797	0.257±0.074		0.200±0.068		0.7539		0.256±0.070		0.231±0.067		1.000		0.53
Fatigue [n (%)]	0.421±0.080	0.395±0.079	1.0000	0.371±0.082		0.229±0.071		0.1797		0.410±0.079		0.462±0.080		0.754		0.28
Heavy limbs [n (%)]	0.579±0.080	0.421±0.080	0.1460	0.486±0.084		0.400±0.083		0.5811		0.538±0.080		0.359±0.077		0.039		0.72
Vomiting/phlegm [n (%)]	0.316±0.075	0.210±0.066	0.3877	0.086±0.047		0.343±0.080		0.0117		0.385±0.078		0.359±0.077		1.000		0.004
Bloating [n (%)]	0.474±0.081	0.368±0.078	0.2188	0.400±0.083		0.200±0.068		0.0923		0.256±0.070		0.410±0.079		0.250		0.03
Taste changes [n (%)]	0.237±0.069	0.105±0.050	0.1797	0.114±0.054		0.429±0.084		0.007		0.128±0.053		0.231±0.067		0.219		0.001
Syrigmus [n (%)]	0.368±0.078	0.289±0.074	0.4531	0.343±0.080		0.200±0.068		0.2668		0.205±0.065		0.179±0.061		1.000		0.65
Reduced appetite [n (%)]	0.132±0.055	0.158±0.059	1.0000	0.057±0.039		0.200±0.068		0.1797		0.308±0.074		0.436±0.079		0.125		0.36
Ventosity [n (%)]	0.342±0.077	0.316±0.075	1.0000	0.229±0.071		0.086±0.047		0.125		0.385±0.078		0.333±0.075		0.754		0.41
Lower limb edema [n (%)]	0.184±0.063	0.237±0.069	0.6875	0.257±0.074		0.314±0.078		0.7744		0.205±0.065		0.077±0.043		0.0625		0.008
Loose stools [n (%)]	0.368±0.078	0.289±0.074	0.5078	0.343±0.080		0.086±0.047		0.0225		0.308±0.074		0.487±0.080		0.039		0.001

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