Hyperlipidemia HDL, LDL, Red Yeast Rice (Monascus purpureus)

[herbsandhelpers]

RESEARCH

Extracts of Chinese red yeast rice (RYR, a traditional dietary seasoning of Monascus purpureus) contains several active ingredients including lovastatin, and several trials of its possible lipid-lowering effects have been conducted. This meta-analysis assesses the effectiveness and safety of RYR preparations on lipid modification in primary hyperlipidemia. We included randomized controlled trials testing RYR preparation, compared with placebo, no treatment, statins, or other active lipid-lowering agents in people with hyperlipidemia through searching PubMed, CBMdisk, TCMLARS, the Cochrane Library, and AMED up to December 2004. Ninety-three randomized trials (9625 participants) were included and three RYR preparations (Cholestin, Xuezhikang and Zhibituo) were tested. The methodological quality of trial reports was generally low in terms of generation of the allocation sequence, allocation concealment, blinding, and intention-to-treat. The combined results showed significant reduction of serum total cholesterol levels (weighted mean difference -0.91 mmol/L, 95% confidence interval -1.12 to -0.71), triglycerides levels (-0.41 mmol/L, -0.6 to -0.22), and LDL-cholesterol levels (-0.73 mmol/L, -1.02 to -0.043), and increase of HDL-cholesterol levels (0.15 mmol/L, 0.09 to 0.22) by RYR treatment compared with placebo. The lipid modification effects appeared to be similar to pravastatin, simvastatin, lovastatin, atorvastatin, or fluvastatin. Compared with non-statin lipid lowering agents, RYR preparations appeared superior to nicotinate and fish oils, but equal to or less effective than fenofibrate and gemfibrozil. No significant difference in lipid profile was found between Xuezhikang and Zhibituo. RYR preparations were associated with non-serious adverse effects such as dizziness and gastrointestinal discomfort. Current evidence shows short-term beneficial effects of RYR preparations on lipid modification. More rigorous trials are needed, and long-term effects and safety should be investigated if RYR preparations are to be recommended as one of the alternative treatments for primary hyperlipidemia.

STUDY: Red yeast rice extract and heart disease

An “extract used in Chinese meals may be good for the heart”, The Daily Telegraph reports. The extract of Chinese red yeast rice, which “gives Peking duck its red colour”, was found to reduce the risk of dying from heart disease, or having another heart attack, in a study of almost 5,000 Chinese adults who had previously had a heart attack, the newspaper said. It adds that, “deaths from cancer were also reduced by two thirds”.
This large study showed that the extract had a beneficial effect. However, this is not surprising, as one of the original cholesterol-lowering drugs – lovastatin – was originally extracted from yeast rice. The findings about the effects of the extract on cancer deaths are not conclusive and need to be investigated further.

In addition to lovastatin, the extract contains other compounds, and the effects of these on humans have not been fully studied. For this reason – and because plant extracts are not as strictly regulated as medicines – anyone worried about their cardiovascular risk should consult their GP, who can advise them about whether they should start taking a statin, rather than red yeast rice extract. Also, they should not be mislead into believing that eating Chinese takeaways – many of which have a high fat content – will reduce their risk of heart disease.

Where did the story come from?

Dr Zongliang Lu and colleagues from the Chinese Coronary Secondary Prevention Study Group carried out this research. The study was funded by the Chinese National Scientific and Technological Projects and WBL Peking University Biotech Co. Ltd, the manufacturers of the extract used in the study. It was published in the peer-reviewed medical journal: American Journal of Cardiology.


What kind of scientific study was this?

This was a randomised placebo-controlled trial looking at the effects of Xuezhikang (XZK), an extract of red yeast rice, on heart health in people who had previously suffered a heart attack. This extract contains lovastatin, which is one of the statin drugs known to reduce “bad” cholesterol in the blood and reduce the risk of cardiovascular events.

The researchers enrolled 4,870 Chinese adults (3,986 men and 884 women, aged 70 years or younger) who had experienced a heart attack in the previous five years and been treated at one of 65 hospitals in China. Only people with average levels of low-density lipoprotein (LDL or “bad” cholesterol) in their blood were included. Those who had serious heart problems, high blood pressure, previous stroke, uncontrolled diabetes, liver or kidney disease, cancer, a history of alcohol or drug abuse, or women who might become pregnant, were not included in the study.

"Long-term therapy with XZK significantly decreased the recurrence of coronary events"
Zongliang Lu, lead author

All participants ate a controlled diet for four weeks and were taken off any medications they were using to control their cholesterol. After this period, the level of cholesterol in their blood was measured, and they were randomly assigned to receive either two 300 mg XZK capsules (containing 5 to 6.4mg of lovastatin plus other compounds) or two inactive (placebo) capsules daily. The participants continued to take the tablets for an average of 4.5 years. They had check-ups six to eight weeks after the study started, and then every six months.

Researchers were mainly interested in major coronary events, such as non-fatal heart attacks or deaths from heart disease. They compared the proportion of people in the XZK group who experienced these events with the proportion in the placebo group. The researchers also looked at the levels of cholesterol in the blood, deaths from non-cardiac causes and any side effects of the treatment.

What were the results of the study?

During the study 139 people in the XZK group (5.7%) experienced major cardiovascular events, compared with 254 people in the placebo group (10.4%). This represented an absolute reduction of 4.7% in major events, or a relative reduction of 45% of events compared with the placebo.

When the researchers looked at cardiovascular mortality alone, they found that XZK reduced cardiovascular mortality by almost a third. XZK reduced “bad” cholesterol levels and increased “good” cholesterol levels. There were no serious side effects related to treatment and people in both groups experienced mild stomach upsets.

What interpretations did the researchers draw from these results?

The researchers concluded that long-term use of XZK reduced cardiovascular events in Chinese people who have previously had heart attacks.

What does the NHS Knowledge Service make of this study?

This study provides good evidence that the red rice extract XZK reduces “bad” cholesterol and subsequent cardiovascular events in Chinese people who have already experienced a heart attack. This finding is not surprising, as this extract contains lovastatin, a cholesterol-lowering compound that is already known to reduce cardiovascular risk. There are a few points to note when interpreting this study:

It was unclear how the researchers identified what had happened to those people who did not attend their scheduled check-ups. It is possible that they missed people who had suffered cardiovascular events if they did not check hospital records.
It was also unclear whether the researchers obtained independent verification of diagnoses of major cardiovascular events, or how they identified causes of death.
As well as their main outcome – major cardiovascular events – the researchers also looked at a number of other outcomes. One of the findings, mentioned by the newspaper, is that deaths from cancer were reduced by two thirds. There are a number of reasons why this finding should be interpreted with caution: firstly, it is not known how these cancer deaths were identified and verified; secondly, cancer deaths were not the main focus of the paper and therefore the results can only be seen as preliminary; thirdly, as there were a number of outcomes tested, it is more likely that a statistical difference was found by chance. This finding will need to be confirmed by other studies looking specifically at this effect.

As the authors of the study acknowledge, this extract contains compounds other than lovastatin that may contribute to its effects. These compounds “have not as yet been adequately isolated, analysed, and characterised for their consistency, stability, and individual pharmacologic and other properties and, therefore, require further study”.

People tend to think that substances extracted from plants must be better for us than “medicines”, and cannot be harmful. However, this is not the case. The contents of medicines such as statins are carefully tested and regulated, and they contain known concentrations of the active drug. Substances sold as health supplements are not so strictly regulated, therefore their contents may vary widely and cannot be guaranteed to be safe. For this reason, people who are concerned about their risk of heart attack or their cholesterol levels should talk to their GP, who may prescribe them a statin, rather than taking red rice extracts.

Sir Muir Gray adds...

The word "may" is the key word.

USES

High cholesterol
Since the 1970s, human studies have reported that red yeast lowers blood levels of total cholesterol, low-density lipoprotein/LDL ("bad cholesterol"), and triglyceride levels. Other products containing red yeast rice extract can still be purchased, mostly over the Internet. However, these products may not be standardized and effects are not predictable. For lowering cholesterol, there is better evidence for using prescription drugs such as lovastatin.

Coronary heart disease
Preliminary evidence shows that taking Monascus purpureus by mouth may result in cardiovascular benefits and improve blood flow. Additional study is needed before a firm recommendation can be made.

Diabetes
Early human evidence suggests the potential for benefits in diabetics. Additional study is needed before a firm recommendation can be made.

DOSAGE

Adults (18 years and older)
1,200 milligrams of concentrated red yeast powder capsules have been taken two times per day by mouth with food.
The average consumption of naturally occurring red yeast rice in Asia has been reported as 14-55 grams per day.

Children (younger than 18 years)
There is not enough scientific evidence to recommend red yeast for children.

HISTORY

Red yeast rice (RYR) is a traditional Chinese cuisine and medicinal agent prepared by using Monascus purpureus fermented with rice, which has been recorded in ancient Chinese pharmacopoeia Ben Cao Gang Mu-Dan Shi Bu Yi during the Ming Dynasty (1368–1644)[1]. The extracts from RYR contain starch, sterols, isoflavones, and monounsaturated fatty acids, and other compounds [2,3]; depending on Monascus strains used and fermentation conditions, it may contain polyketides called monacolins [4]. Monacolin K is lovastatin, which is a commonly prescribed lipid-lowering drug. Several randomized clinical trials have indicated beneficial effects of the RYR preparations including Xuezhikang and Zhibituo in the treatment of hyperlipidemia [5-9]. Xuezhikang has been in clinical use as a Chinese proprietary medicine in China and has recently been marketed in several European countries including Norway and Italy. As these preparations contain different compositions and concentration of lovastatin, evaluation of their effectiveness and safety from clinical trials is warranted.

People with hyperlipidemia have responded well to the lipid-lowering agents including HMG-CoA reductase inhibitors (statins), fibrates, nicotinic acids, and n-3 fatty acids [10]. However, long-term safety and potential drug interaction between statins and other hypolipidemic agents may become problematic [11-13]. Nowadays, many people would like to use naturaceuticals instead of chemical drugs. A previous systematic review identified four randomized trials of the lipid-lowering effects of RYR and concluded a lack of sufficient clinical research to support their efficacy [14]. The objective of this review is to assess the beneficial effects of lipid modification and safety of RYR preparations for their use in people with primary hyperlipidemia.

ADVERSE EFFECTS

Seventy-seven trials reported outcomes of adverse effects, and the incidence rate ranged from 1.3% to 36%. The most commonly reported adverse effects were dizziness, low appetite, nausea, stomach-ache, abdominal distension, and diarrhoea. A small proportion of participants suffered from increased serum BUN and ALT levels. The trials did not report serious adverse events.

Allergies
There is one report of anaphylaxis (a severe allergic reaction) in a butcher who touched meat containing red yeast.

Side Effects and Warnings
There is limited evidence on the side effects of red yeast. Mild headache and abdominal discomfort can occur. Side effects may be similar to those for the prescription drug lovastatin (Mevacor®). Heartburn, gas, bloating, muscle pain or damage, dizziness, asthma, and kidney problems are possible. People with liver disease should not use red yeast products.
In theory, red yeast may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. A metabolite of Monascus called mycotoxin citrinin may be harmful.

Pregnancy and Breastfeeding
Prescription drugs with similar chemicals as red yeast cannot be used during pregnancy. Therefore, it is recommended that pregnant or breastfeeding women not take red yeast.

Interactions with Drugs
There are not many studies of the interactions of red yeast rice extract with drugs. However, because red yeast rice extract contains the same chemicals as the prescription drug lovastatin, the interactions may be the same. Fibrate drugs or other cholesterol-lowering medications may cause additive effects or side effects when taken with red yeast. Alcohol and other drugs that may be toxic to the liver should be avoided with red yeast rice extract. Taking cyclosporine, ranitidine (Zantac®), and certain antibiotics with red yeast rice extract may increase the risk of muscle breakdown or kidney damage.

Certain drugs may interfere with the way the body processes red yeast using the liver's "cytochrome P450" enzyme system. Inhibitors of cytochrome P450 may increase the chance of muscle and kidney damage if taken with red yeast.

In theory, red yeast may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

Red yeast may produce gamma-aminobutyric acid (GABA) and therefore can have additive effects when taken with drugs that affect GABA such as neurontin (Gabapentin®).

Red yeast may also interact with digoxin, niacin, thyroid medications, and blood pressure-lowering medications. Caution is advised.
Red yeast may alter blood sugar levels; patients with diabetes or taking insulin or blood sugar-lowering medications by mouth should consult with a qualified healthcare professional, including a pharmacist. Dosing adjustments may be necessary.

Interactions with Herbs and Dietary Supplements
Red yeast may interact with products that cause liver damage or are broken down in the liver. Grapefruit juice may increase blood levels of red yeast. Milk thistle, St. John's wort, niacin, and vitamin A may interact with red yeast rice extract. Coenzyme Q10 levels may be lowered by red yeast rice extract. Cholesterol-lowering herbs and supplements such as guggul or fish oils may have increased effects when taken with red rice yeast. Although not well studied, red yeast may also interact with astaxanthin and zinc. Caution is advised.

Certain herbs and supplements may interfere with the way the body processes red yeast using the liver's "cytochrome P450" enzyme system. Inhibitors of cytochrome P450 may increase the chance of muscle and kidney damage if taken with red yeast.

In theory, red yeast may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba , and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

Red yeast may also interact with digitalis (foxglove), or herbs and supplements that affect the thyroid or blood pressure. It may also have anti-inflammatory effects and should be used cautiously with other herbs or supplements that may have anti-inflammatory effects.
Red yeast may alter blood sugar levels in the blood, and patients with diabetes or taking herbs and supplement to control blood sugar should use with caution.