Because they are distinguished by the highest possible level of reduction in the production of “bad” fat fractions. But the answer to the question of whether statins are harmful or beneficial for cholesterol is not so clear.

Despite the fact that the effectiveness of therapy is at a high level, recently studies have increasingly been published that talk about the dangers of these drugs. They negatively affect the liver and other internal organs. And in the presence of chronic diseases, they can lead to severe side effects. So what should we do? Should I take it to lower cholesterol levels and thereby worsen the general condition of the body, or should I refuse? This will be discussed in this article.

What are satins

These are medications that help reduce the liver's production of cholesterol, which, once released into the blood, has a negative effect on the body. These drugs serve to block certain enzymes that are involved in its production. Thanks to such drugs, the mortality rate from heart attacks has significantly decreased. They really prolong life, especially for sick people whose risk of heart attack is quite high. However, despite all the benefits, they have a fairly extensive list of side effects.

Types of satins

As surprising as it may sound, cholesterol can be divided into two groups: bad and good. Due to an overabundance, it can kill a person. Why is it good? Because without it, the body will not be able to heal even small cuts. That is, it is necessary for the body, but in the proper quantity.

1. Low-quality cholesterol (or in other words, bad) has a low level of density, which is why fat deposits are formed, which have a bad habit of settling on the walls of blood vessels. That is, plaques. It is this cholesterol that can cause harm to the body. What will help? Statins. However, these drugs should not reduce cholesterol levels below 4 mmol/L. If this indicator is violated, you need to consult a doctor and reconsider your diet (in some cases you will have to postpone taking these medications).
2. Good cholesterol is synthesized by the body itself, and it is this that resists the formation of plaques. It moves fats to the liver, where they decompose and are then completely eliminated. In other words, atherosclerosis can be caused not only by high levels of bad cholesterol, but also by low levels of good cholesterol.

Therefore, before using these drugs, you need to conduct a thorough examination. So, statins are of the following types:

When are statins prescribed:

• statins are prescribed for cholesterol levels in the blood of more than 5.8 mmol/l. (only if it cannot be returned to normal after a three-month diet);
• for diseases that cause atherosclerosis;
• for heart pathologies and atherosclerosis - in order to prevent the development of the disease in the future;
• mature people for the purpose of prevention (the older the body, the higher the risk of developing atherosclerosis);
• for young people as a preventive measure (only if there are people in the family suffering from hereditary heart disease).

According to American experts, it is necessary to prescribe such drugs at more than 3.5 mmol/l in the blood, but only if the patient has a risk of ischemic heart damage: diabetes, old age, genetics, hypertension, obesity or male gender.

Before prescribing drugs, the patient must undergo a complete examination (otherwise it will not be possible to provide full treatment). Thanks to the obtained tests, the specialist assesses the patient’s health status and determines the advisability of using statins.

Attention! Self-treatment with these drugs is strictly prohibited!

Prevention of heart attack

Due to the removal of plaque, these drugs have a good effect on the cardiovascular system. With regular use, life expectancy increases. None of the drugs on the market today can reduce the incidence of heart attacks as much as statins.

However, when using these drugs, do not forget about proper nutrition. It is also important to regularly monitor your blood pressure, quit smoking and get rid of other bad habits, often walk in the fresh air, play sports, minimize stressful situations, try to devote as much time as possible to your hobbies and interests.

Natural statins

Especially for those people who, for certain reasons (due to fear of side effects), refuse these drugs, we have prepared completely safe analogues - natural statins for cholesterol, which are found in food. These include:

• niacin (represents vitamin B3 or PP) - found in large quantities in nuts, meat, red fish;
• curcumin – the largest amount is found in turmeric;
• policosanol – found in sugar cane, these vitamins are sold in capsule form;
• ascorbic acid - to replace this drug, use large quantities of rosehip tincture, various types of peppers, currants, sea buckthorn, cabbage and citrus fruits;
• resveratrol - the main ingredients of this drug are found in sufficient quantities in grape skins or red wine;
• fatty acids – found in fatty fish and vegetable oils;
• dietary fiber - found in cereals, bread, cabbage, beans, apples, carrots.

Garlic and soy products: tempeh or miso can also serve as substitutes for statins.

Regular consumption of these products significantly increases blood levels. And on an ongoing basis it will bring it back to normal.

How to use

Having assessed the harm and benefits of statins, the patient himself has the right to decide whether he should take these drugs or, conversely, refuse. At the same time, when making decisions, you need to soberly assess all the risks to your health, including those that may arise without the use of these medications.

So, when taking statins, it is important to know:

• in certain cases, taking these drugs is necessary for life; without them, the patient’s well-being will significantly worsen;
• self-prescription of drugs is strictly prohibited: which drug is suitable for the patient is determined by the doctor, based on his medical history, as well as the presence of chronic diseases;
• In order for the treatment to be effective and without side effects, it is necessary to follow the dose prescribed by the doctor;
• if the medicine prescribed by the doctor is not affordable for the patient, the possibility of replacing it is negotiated with a professional;
• the doctor prescribes the frequency (these recommendations must be followed unquestioningly);
• if there are any changes in the liver, you need to take Rosuvastatin, its harm to the body is minimal;
• Also, during treatment you should carefully monitor your diet; antibiotics and alcohol should not be taken;
• Satins are not compatible with many medications.

How harmful is taking statins?

According to pharmaceutical companies, the benefits of these drugs far outweigh their harm. But the opinion of independent researchers differs significantly. They believe that the harm they cause to the human body is much greater than the benefit.

Naturally, these drugs bring both harm and benefit. Therefore, they should be taken only after diagnosis and in consultation with a doctor. The specialist will determine the dosage necessary for the patient, which will cause minimal harm and at the same time benefit the body. Whether to listen to a professional or not is everyone’s business.

Many people do not suspect how harmful satins are and begin to prescribe these drugs on their own. The danger is that the harm from them does not appear immediately. It is for this reason that doctors strongly recommend regular tests to check your health status if you are constantly using statins.

Now let's take a closer look at how these drugs act on certain organs.

How do statins act on the brain?

The drug can affect the brain, which is very dangerous (although isolated cases occur in practice). Studies that were conducted back in 2002 showed that long-term use of these medications increases the risk of polyneuropathy.

Most patients who take satins for a long time experience problems with the vestibular system, speech disorders, and an increased level of fatigue. The first signs of the bad effects of statins on the body are sleep disturbances. This is followed by impairments in cognitive function and fine motor skills. They also contribute to memory impairment. As a rule, after stopping taking the drugs, these symptoms disappear.

What is the effect of statins on the heart?

By significantly reducing cholesterol levels, these drugs have a beneficial effect on the heart. Thanks to cholesterol, the functioning of the heart muscle is significantly improved. There are no more “obstacles” in her path. It works fully and stimulates the work of other organs, thereby significantly improving the general condition of a person.

Taking statins increases the risk of developing cataracts

After studies conducted in 2013, which involved 46 thousand people, it turned out that those people who took the drug for 2 years were twice as likely to suffer from cataracts than those who did not take it.

BUT! Another study showed the exact opposite result: people who took these medications had much less cataracts than those who did not take them.

It is worth noting that in both cases, the results are not so significant as to completely prohibit the use of statins or, conversely, encourage them in patients with a high risk of cataracts.

Statins are bad for memory

Initial experiments were carried out on rats. As a result, it turned out that the drugs still have a bad effect on memory.

Interestingly, before the experiment began, the rodents were given a task that consisted of finding the place where the treat was located. After taking statins for a week, the animals began to forget where the food they had hidden was located. After the end of the experiment, the memory problems disappeared. Such behavior is equivalent to the actions of a person who himself put his keys somewhere and then forgot where exactly.

BUT! Long-term use of these medications still leaves a mark, worsening the patient’s working memory.

Despite all the research, statins are really necessary for a sick person, in some cases they save lives. Therefore, their benefits (saving lives) far outweigh the side effects. Statins lower cholesterol levels in the brain (where a quarter of this “stuff” is located). That is, after the drug is introduced into the brain, it will begin to affect nerve cells, which will subsequently help reduce cholesterol levels in the body.

Side effects

These drugs have a lot of side effects, namely:

1. The digestive system can cause the following problems: diarrhea, anorexia, vomiting, pancreatitis, jaundice.
2. Dizziness, paresthesia, amnesia or hypoesthesia, as well as general malaise may occur.
3. Allergic reactions are possible, namely: anaphylaxis, skin itching, skin rash, erythema, urticaria, Lyell's syndrome.
4. Complications from the musculoskeletal system may include back pain, myositis, arthritis or seizures.
5. Metabolism: low sugar levels, obesity, impotence.
6. Circulatory system: thrombocytopenia.

However, the above symptoms are extremely rare. The most common symptoms that bother patients are: nausea, insomnia, flatulence, constipation, headache, diarrhea.

How to replace statins if there are contraindications

Before you wonder how to replace statins to lower cholesterol, take a close look at your lifestyle. If he is more often lying down or sitting - then nothing! Only pills. A healthy lifestyle will help replace these drugs. Naturally, if cholesterol levels go off scale, you cannot completely stop taking medications.

The main thing is to have full information about your health (which you can ask your doctor about). If a person is not keen on sports and does not eat properly, it is unlikely that he will be able to avoid taking statins.

Before you switch to a healthy lifestyle as a way off statins, ask your doctor what's causing your blood cholesterol levels to be so high. Why is the body unable to independently control its level, and where does it even come from? Then ask them to tell you what exactly the lowering effect these drugs give.

As soon as the cause can be eliminated, you can continue the path forward. You can replace statins with a full healthy life. You should not eat fatty foods that are high in animal fats (one of the sources of cholesterol). Naturally, you need to forget about the existence of mayonnaise. Favorite fried foods should be replaced with healthy foods that contain a lot of fiber. It is worth playing sports more often or at least walking (the more physical activity, the faster cholesterol goes away). In addition, training improves tone and mood.

After completely giving up satins and replacing these drugs with a healthy lifestyle, take a blood test after 4 to 5 months. If the results are not encouraging, perhaps the problem is serious and requires the introduction of special treatments or changes in the menu.

In some cases, you cannot completely stop taking pills. For example:

• high blood pressure;
• bad heredity;
• with coronary heart disease;
• old age: from 70 years and above;
• obesity;
• diabetes.

IMPORTANT! Preferring traditional methods to reduce cholesterol levels in the body, you need to forever forget about bad habits, primarily smoking.

If you have high cholesterol, you need to get tested every 5-6 months (despite the fact that you lead a healthy lifestyle or take statins). Perhaps, after the results obtained, when your cholesterol levels return to normal, you will be able to return to your normal lifestyle, without pills and their side effects.

When prescribing various drugs, you need to think about how they generally affect the body. Using statins for the liver can also affect other organs and tissues, and not always positively.

The widespread use of statins or HMG-CoA reductase inhibitors to reduce the risk of heart attack and stroke has significantly reduced the number of such diseases and is a method of preventing their recurrence. This effect is associated with the effect of the drugs on the level of cholesterol in the blood, which decreases due to a decrease in its synthesis in the liver. How safe statins are for the liver is discussed and studied in many countries. Let's consider the effect of these drugs on liver tissue and the body as a whole.

The discovery of a connection between high levels of serum cholesterol in the blood and the risk of heart and vascular diseases led to the development of methods for reducing it. The discovery by Japanese scientists of the biochemical cycle of cholesterol formation made it possible to create drugs that interrupt its synthesis. They were called statins.

Studies show that the use of statins to prevent recurrent heart attack significantly reduces the risk of its occurrence by reducing blood cholesterol, mainly the low-density lipoprotein (LDL) fraction. Against this background, the amount of high-density lipoproteins (HDL), which are able to remove excess cholesterol and prevent the development of vascular atherosclerosis, increases.

The feasibility of their use to reduce the risk of developing such serious diseases as heart attack and stroke is still being studied, since statins, in addition to lowering cholesterol, have a number of side effects that can be life-threatening for the patient.

Mechanism of action

Statins stop the biochemical synthesis of cholesterol in liver cells at one of the first stages - the stage of transition of hydroxymethylglutoryl (HMG-CoA) to mevalonate. They are an inhibitor of HMG-CoA reductase, an enzyme that regulates this process. This reduces the amount of cholesterol in hepatocytes and causes increased activity of the cell's LDL receptors.

Cholesterol, part of the low-density lipoprotein complex, enters the liver cells, which reduces its content in the blood. Thus, the level of serum cholesterol is reduced by reducing the LDL fraction. Since it is the increase in LDL in the blood that is a predisposing factor to the development of atherosclerosis, there is an undoubted benefit from the action of HMG-CoA reductase inhibitors.

In addition, they reduce the synthesis of low-density lipoprotein precursor apolipoprotein B-100 and triglyceride-rich lipoproteins, which also affects serum cholesterol. This has been proven by the fact that when these drugs are used in patients with familial hypercholesterolemia who do not have LDL receptors, serum cholesterol decreases.

There is also evidence of the effect of HMG-CoA reductase inhibitors on the vascular endothelium; they reduce thrombus formation and can cause a decrease in blood clotting; an anti-inflammatory effect is also noted.

Adverse Impact

Cholesterol is formed from acetyl-CoA, the suppliers of which are glucose and fatty acids; the cessation of its synthesis leads to disruption of the metabolism of fatty acids, their deposition in cells with the formation of lipid vesicles. This can negatively affect hepatocytes and cause their destruction.

Normally, the activity of HMG-CoA reductase is reduced by the action of cholesterol itself, bile acids and glucagon, and increased by the influence of insulin. Their use leads to a violation of this dependence. Often, excess insulin appears in the blood of patients (hyperinsulinemia), as a compensatory reaction to a decrease in cholesterol synthesis. There is evidence that long-term hyperinsulinemia can lead to the development of diabetes mellitus.

Metabolism of statins occurs with the participation of cytochromes P-450, which also provide the synthesis of steroid hormones, vitamin D, and are involved in the peroxidation of unsaturated fatty acids, so increased doses can lead to a deficiency of cytochromes P-450, which affects the entire body.

Side effects

They are quite rare, the development is associated with a disruption of the cholesterol formation cycle, this causes:

• changes in fatty acid metabolism in liver cells;
• reduction of its metabolic products in the body;
• hyperinsulinemia;
• a sharp decrease in cholesterol.

Cholesterol, in addition to its harmful effect on blood vessels, is necessary for the synthesis of cell membranes, steroid hormones, and bile, so its sharp decrease can have an adverse effect on the body. In addition, changes in fat metabolism in hepatocytes can lead to the accumulation of lipids in cells and their damage, and hyperinsulinemia can lead to the development of diabetes mellitus.

Side effects from the use of HMG-CoA reductase inhibitors, in addition to individual intolerance and allergic reactions, can cause:

• acute liver failure;
• systemic muscle tissue disease (rhabdomyolysis);
• acute renal failure;
• diabetes;
• memory and thinking disorders;
• endocrine diseases.

According to statistics, such complications occur rarely and are more often associated with the use of increased doses of HMG-CoA inhibitors. Therefore, they can be used only as prescribed by a doctor, and the amount of drugs is selected individually, with regular monitoring of biochemical blood tests.

Effect on the body

Under the influence of statins, the amount of LDL in the blood decreases, but too low a level can cause a disruption in the synthesis of cell membranes, myelin fibers, and steroid hormones. During use, cases of memory and thinking disorders resembling Alzheimer's disease have been observed. Low concentrations of LDL can cause aggression and depression.

Such changes are possible when using large doses of drugs, but liver and muscle disorders are more common. Fatty liver disease causes damage to its cells, but their high reparative ability usually completely compensates for the hepatotoxic effect.

Systemic damage to muscle tissue, the mechanism of which is unclear, can cause acute renal failure; it is associated with the fact that the kidney tubules become clogged with myoglobin from destroyed muscle cells.

It is necessary to start taking small doses under the control of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK) and lipoproteins in the blood.

A biochemical blood test is done every month. Based on these indicators, the dose of the drug is gradually increased so that the LDL level decreases to normal values. Its strong decrease can cause disruption of vital structures of the body.

An increase in ALT and AST is often observed when taking HMG-CoA inhibitors; this may be due to damage to some hepatocytes. Gradually, the levels of ALT and AST in the blood return to normal. But if after prescription the level of ALT and AST increases more than 3 times, the dosage of the drug must be reduced or discontinued. A high level of these enzymes in the blood may indicate massive death of hepatocytes, which causes acute liver failure.

An increase in creatine phosphokinase in the blood is an indicator of muscle tissue damage and a complication such as rhabdomyolysis.

Effect on liver cells

Acute liver failure with statins does not occur as often, and the ability to reduce the risk of developing cardiovascular diseases is high, so they continue to be used. What changes do HMG-CoA inhibitors have on liver cells?

The reasons that cause the death of hepatocytes are discussed above. But fatty liver, non-alcoholic or alcoholic, occurs against the background of increased LDL. Therefore, the prescription of HMG-CoA inhibitors for these diseases is justified. Research shows which statins are the safest for hepatocytes in this situation. Of particular importance is the hydrophilicity of the molecule of HMG-CoA inhibitors, therefore, for liver diseases, they try to prescribe Rosuvastatin, Pravastatin, Fluvastatin.

But, in addition to fatty degeneration, HMG-CoA inhibitors also have other effects on the liver. Their anti-inflammatory effect helps stop inflammation in hepatocytes, which causes connective tissue proliferation and cirrhosis.

The use of HMG-CoA inhibitors in patients with viral hepatitis, which infects 400 million people on earth, has shown a reduction in the risk of developing liver cancer in almost 50% of cases.

Reduced coagulation and thrombus formation, a beneficial effect on the vascular endothelium, reduces blood pressure in the portal veins, which also helps to suppress inflammatory processes in the liver tissue. Of this group of drugs, the most effective in affecting the vascular endothelium are Simvastatin and Lovastatin; they activate the NO synthetase gene, and NO protects endothelial cells.

Features of application

HMG-CoA inhibitors can only be taken if prescribed by a doctor. After an examination and blood tests, your doctor can decide which medications will be most effective and safe. Self-administration of these drugs is fraught with consequences.

1. It is difficult to choose an individual dosage.
2. They should not be taken for certain diseases.
3. To reduce the risk of side effects, combining them with other cholesterol-lowering drugs (fibrates, Ezetimibe, lipoic acid) is recommended.
4. Some medications may increase the side effects of HMG-CoA inhibitors (antifungals, antihypertensives, antigout).

Increased side effects occur when HMG-CoA inhibitors are prescribed with cytochrome P-450 inhibitors. HMG-CoA reductase inhibitors and drugs such as:

• Erythromycin;
• Intraconazole;
• Verapamil;
• Diltiazem;
• Clopidogrel and others.

In addition, the advisability of using it to lower blood cholesterol depends on age, bad habits, and concomitant diseases.

For patients with liver pathologies, Rosuvastatin and Pravastatin are usually recommended. An important condition for their appointment is the abstinence from alcoholic beverages. Even small doses of alcohol are a burden for liver cells. You should also not combine these medications with antibiotics. In order to reduce the dosage of drugs as much as possible, it is advisable to follow an anti-cholesterol diet.

Despite the possibility of developing side effects, statins are prescribed for metabolic and alcoholic diseases of the hepatobiliary system, in order to slow down fatty degeneration by reducing serum cholesterol in the blood. Their use is justified and gives good results.

Cardiovascular diseases are a major medical problem. They are the ones that most often lead a person to death, and it is for them that scientists around the world are tirelessly looking for cures.

It is now known that the key cause of heart attacks is the adhesion of cholesterol plaques to the walls of blood vessels and the formation of blood clots from the same cholesterol. To combat low-density lipoproteins (cholesterol), back in the 70s of the last century, Japanese scientist Akiro Endo developed a special drug. True, he did not receive any money for his discovery, but pharmaceutical companies, which, based on the scientist’s invention, began to produce synthetic statins, became rich.

To date, 6 types of statins are known. These are Atorvastatin and Rosuvastatin, Pravastatin and Fluvastatin, Simvastatin, as well as a combination of Simvastatin and Ezetimabe. Thanks to extensive advertising, these incredibly popular drugs are considered the best remedies for vascular problems and the development of heart attacks. It’s no wonder that today every 4th person in the world who has reached the age of 45 takes them!

But statistics show that an increase in statin intake has not led to a decrease in heart attacks and strokes. On the contrary, the number of people facing complications of cardiovascular diseases is steadily growing. All this leads to the idea that statins are not able to resist vascular damage and even worsen the existing situation. And today there are many prerequisites for refusing to take statins. Let's study them.

Why you shouldn't take statins

1. Does not relieve cardiovascular diseases
The main purpose of statins is to reduce cholesterol levels, which is a serious factor in the development of cardiovascular pathologies. However, high cholesterol, although important, is by no means the only cause of heart disease. These diseases are caused by the development of diabetes, constant stress, lack of physical activity, arterial hypertension, smoking and many other serious factors. Is this why taking statins does not improve statistics on reducing heart and vascular diseases?

Medical experts have even come to the conclusion that only 1% of patients benefit from taking statins. That is, out of 100 patients who regularly take these drugs, the risk of heart attack or stroke is seriously reduced in only one person! The fact is that when advertising these pharmacological agents, manufacturers appeal to indicators of the so-called “relative risk”, which say absolutely nothing about the actual danger threatening them.

2. Reduce Coenzyme Q10 levels
It turns out that long-term use of cholesterol-lowering drugs leads to depletion of Coenzyme Q10 reserves. But this enzyme is called the element of health and youth, since thanks to Coenzyme Q10, the energy level in the body is maintained and cellular respiration is carried out. But as the reserves of this enzyme are depleted, serious changes occur in the body: muscles become flabby, skin gradually fades, hair dries out, and nails break.

But this is not the most dangerous thing. Few people understand that the so-called “bad” cholesterol does not exist in nature! Problems for the body are created by the oxidized version of low-density lipoproteins, and cholesterol oxidation occurs only when the level of a powerful antioxidant called Coenzyme Q10 decreases in the body. That is, by taking statins, we not only do not prolong our life, but on the contrary, we provoke dangerous conditions that can lead to death! Can this be avoided? Of course, you can, but to do this, you need to take nutritional supplements containing Coenzyme Q10 at the same time as statins. And people who have crossed the 40-year mark should replace Coenzyme Q10 with the drug Ubiquinol.

3. Reduce vitamin K2 levels
The results of the studies published in the journal Clinical Pharmacology surprised and puzzled the scientific community. If previously there was no doubt that statins remove “bad” cholesterol from the body and reduce the likelihood of atherosclerosis, then a study by Swedish scientists showed that this is not so. Moreover, evidence has emerged that statins provoke the development of heart failure! And the main physiological mechanism leading to such consequences is a decrease in the level of vitamin K2 in the body.

It turns out that vitamin K2 is the main regulator of calcium. It not only delivers calcium to our bones and teeth, but also removes excess of this trace element from the arteries and soft tissues. A decrease in the level of this vitamin can create serious problems for the body, triggering the development of calcification - a condition in which liquid calcium salts turn into a solid state. Thus, vitamin K2 deficiency leads to the appearance of kidney stones, the development of osteoporosis, cardiovascular diseases, heart attack and stroke. This problem should be combated by supplementing statin treatment with taking a multivitamin complex containing vitamin K2.

4. Reduce the production of ketone bodies
Statins lower cholesterol levels by inhibiting the liver's production of certain enzymes. However, this process also has a reverse, extremely negative side. From these enzymes, the body produces the substance Coenzyme Q10, which is much needed by the body, as well as ketone bodies, which nourish the components of the body’s cells - mitochondria. These same mitochondria are real energy storehouses that support our vitality. With a reduction in their number, metabolic processes slow down significantly, which leads to serious health problems and the gradual decline of the body. And if to replenish Coenzyme Q10 during treatment with statins, it is enough to take supplements with this enzyme, then to replenish the reserves of ketone bodies you will have to go on a special ketogenic diet.

5. Increase the risk of pathologies
Given that statin use seriously depletes the body of nutrients by minimizing levels of Coenzyme Q10, vitamin K2 and ketone bodies, this process leads to the development of serious diseases over time. Let's list some of them.

Cancer
A study by Israeli scientists showed that taking drugs from this group for 10 years or more doubles the risk of breast cancer and carcinoma. Moreover, with an increase in the accumulated dose of the drug, the likelihood of developing prostate cancer significantly increases.

Diabetes
If you take statins for a long time, the likelihood of developing diabetes increases 10 times. Moreover, these drugs trigger several pathogenic mechanisms at once, leading to this dangerous disease. In particular, they increase glucose levels, because as a result of inhibition of enzyme production by the liver, this organ is forced to send sugar back into the body. Moreover, by removing vitamin D from the body, statins increase insulin resistance.

Neurodegenerative pathologies
Our brain is approximately 25% cholesterol and constantly needs to be fed with this lipoprotein to maintain connections between neurons. And if, with long-term use of statins, the amount of cholesterol in the body decreases, a person begins to have memory problems. However, that's not all. To date, it has been proven that ketone bodies protect the body from serious neurodegenerative diseases (Alzheimer's disease or Parkinson's disease). Accordingly, taking statins, which reduce the production of these bodies, significantly increases the risk of each of these diseases.

Diseases of the musculoskeletal system
When taking the medications in question systematically, the likelihood of developing myalgia, seizures, or even autoimmune muscle diseases increases. According to scientists, the cause of such pathologies may be a violation of protein metabolism, which prevents oxidative processes in muscle tissue.

Is there an alternative to statins?

You need to understand that taking statins is by no means the only way to lower cholesterol levels and strengthen the cardiovascular system. There are several useful recommendations that, if followed, will protect you from cholesterolemia and atherosclerosis. Here are some of them:

• completely avoid foods containing fructose, avoid sugar and light carbohydrates if possible, and minimize the consumption of grains containing gluten;
• try to eat mostly raw foods;
• give up vegetable oils and harmful trans fats, replacing them with healthy olive and coconut oil. Remember, olive oil should only be consumed cold;
• Try to eat fermented foods daily, such as sauerkraut, sour cucumbers, kefir, whey or yogurt. This will increase overall immunity and improve the digestive process, which means it will contribute to heart health;
• Get outside more often in sunny weather to maintain your vitamin D levels. This vitamin plays an important role in preventing the formation of cholesterol plaques;
• Regularly consume sea fish, shrimp, krill oil and other foods rich in Omega-3 polyunsaturated fatty acids. Research shows that 500 mg of Omega-3 per day can reduce the level of “bad” cholesterol in the blood and increase the level of beneficial HDL;
• take care of proper rest so that your sleep lasts approximately 8 hours a day;
• stop smoking and drinking alcohol;
• exercise regularly, and introduce high-intensity exercises performed at intervals into your exercise program;
• Practice stress management techniques.

These simple rules will allow you to prevent an increase in the level of bad cholesterol without taking statins, which in fact turned out to be not such safe drugs.
Health to your heart!

This information is provided for informational purposes only, and does not serve as a basis for making any drastic decisions without consulting your doctor.

Statins and the liver: safety

Belarusian Medical Academy of Postgraduate Education

Statins and liver: safety

Silivonchik N.N.

Along with the undeniable positive effects of statins in reducing the risk of cardiovascular diseases and complications, side effects are the subject of attention of specialists and consumers, and one of the most discussed problems within the safety of statins is the hepatic effects. Many years of extensive experience in the use of statins, which were introduced into clinical practice in 1986, and a huge number of studies have made it possible to accumulate an evidence base and show the safety of their use, including in patients with liver diseases, and create practical recommendations for their use.

Specific effects of statins on the liver

Statins are reversible inhibitors of the microsomal enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), a key enzyme in the cholesterol (CS) synthesis cascade that converts HMG-CoA to mevalonate in the liver.

All statins affect the liver: the liver is 1) the target organ for statins, since hepatocytes are the main site of cholesterol biosynthesis, lipoprotein production and catabolism of low-density lipoproteins (LDL) and 2) the site of statin metabolism.

Specific effect of statins on the liver as a target organ. The use of any statins may be accompanied by an asymptomatic increase in blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels by 3 times or more compared to the upper limit of normal. A similar effect is observed for other liver enzymes - alkaline phosphatase, gammaglutamyl transpeptidase and bilirubin. Features of an asymptomatic increase in transaminases: 1) transient nature, 2) development of symptoms in the first 12 weeks of treatment, 3) lack of correlation of biochemical abnormalities with histopathological changes in the liver, 4) lack of predictive value regarding liver tissue damage.

The mechanism for increasing trans-aminase levels is unclear. It is believed that this occurs as a result of changes in the lipid components of the hepatocyte membrane, leading to an increase in its permeability with subsequent “leakage” of liver enzymes and penetration into the blood. This effect is inherent not only to statins, but also to other effective lipid-lowering drugs. To more fully define the phenomenon of abnormal liver enzymes in the absence of hepatotoxicity, the term “transaminitis” has been adapted.

Read the article for patients about the side effects of statins on http://centr-zdorovja.com/statiny-pobochn-effekty/ . Find out how dangerous statins are for the liver, whether these drugs increase blood sugar, and what other problems they cause. Determine whether you need to take these pills or not. Understand how to neutralize the side effects of statins so you don't suffer from weakness, muscle pain, memory problems and concentration problems.

Hepatic metabolism of statins. The metabolism of statins in the liver requires certain components. Transport functions of the liver in relation to statins, as well as a number of other drugs, are carried out using transporters: OATP1B1 (Organic anion transporting polypeptide 1B1), P-go and MRP2. Elimination of all statins with the exception of pravastatin occurs through oxidation by cytochrome P450 enzymes. Different statins are metabolized by different enzymes: lovastatin, simvastatin, atorvastatin - CYP3A4, fluvastatin - CYP2C9; pravastatin is excreted unchanged.

Transport and elimination of statins are considered to be the basis for drug interactions and the safety of both statins and other concomitantly used drugs.

Features of transaminitis

Studies of transaminitis concern its frequency, dependence on statin doses, reversibility and the possibility of re-prescribing statins, and its relationship with the severity of the lipid-lowering effect.

Prevalence. The incidence of asymptomatic transaminase elevations in multiple studies with different types of statins does not exceed 3% for all statins, regardless of their pharmacokinetic characteristics. Most studies show no difference in the incidence of transaminase elevations between statins and placebo. Thus, P. Thavendiranathan et al. (2006) based on an analysis of the Cochrane Collaboration, American College of Physicians Journal Club databases (42,848 patients) did not establish a significant increase in the incidence of elevated liver enzymes.

The role of statin dose. There is evidence and an established point of view that there is a direct relationship between the dose of statins and the frequency of transaminitis: 1% at low doses, 2-3% at medium and high doses. Thus, according to a meta-analysis by M. Silva et al. (2006), the relative risk (RR) of high doses of statins compared with low doses is 4.48 (95% CI 3.27-6.16, R<0,001) . Согласно результатам метаанализа J.H. Hey-Hadavi et al. (2006) безопасности различных доз аторвастатина (10, 20, 40 и 80 мг/сут), выявлена зависимость между частотой печеночных побочных эффектов и дозой: частота подъема трансаминаз была соответственно 0,1%, 0%, 0,2%, 0,5% (в группах плацебо - 0,2%) . The National Lipid Association Statin Safety (США) констатирует, что частота бессимптомного повышения уровня трансаминаз при использовании начальных или средних доз не превышает 1%; этот показатель повышается до 2-3% при использовании любого статина в дозе 80 мг/сут . Вместе с тем в ряде исследований доказательств этого не получено (табл. 1).

Table 1. Relationship between the frequency of increased transaminases and the dose of statins

Although an association between elevated hepatic effects and statin dosage has been observed in a number of studies, the precise correlation between dosage and hepatic complications has not been determined.

Reversibility. In most cases, transaminitis resolves spontaneously without the need to discontinue the statin, probably due to adaptation or tolerance. An increase in laboratory values ​​is usually transient and disappears on its own with interruption, dose reduction, or even continuation of treatment without reducing them, as has been shown in many studies - about 70% of cases of increased transaminase levels after starting treatment with statins resolved independently. This fact has led many clinicians to support the concept of returning the same or a different statin after resolution of elevated transaminase levels and subsequent normalization.

M. Law and A. R. Rudnicka (2006), having analyzed the results of statin use in 180 thousand patients included in 21 large clinical trials lasting an average of about 3 years, indicated that the frequency of increases in biochemical liver tests by 3 times or more according to a single analysis reached 300 cases per 100 thousand person-years, and when taking into account the results of two consecutive analyzes it decreased to 100 cases per 100 thousand person-years (in the placebo groups it was 200 and 40 cases, respectively). According to The National Lipid Association Statin Safety, when assessing the causes of elevated transaminases in patients taking statins, pronounced and persistent increases in transaminase levels are often associated with drug interactions, as well as the presence of concomitant diseases and the use of the highest dose of statins.

Relationship with the severity of the lipid-lowering effect. Some studies have shown a connection between an increase in transaminases and a decrease in LDL-C, while others have shown its absence.

Hepatotoxicity of statins

Criteria for statin hepatotoxicity, incidence and risk, nature and mechanism of liver injury, serious side effects, and risk of acute liver failure (ALF) are reviewed.

Criteria for evaluation. The main signs of hepatotoxicity of drugs are laboratory test abnormalities, but there are no standardized criteria for assessing statin-related abnormalities. Post-marketing studies usually define drug-induced hepatotoxicity as an increase in ALT of more than two to three norms or conjugated bilirubin of more than two norms. A number of researchers take into account deviations in biochemical tests as a clinically significant manifestation of statin hepatotoxicity only if the ALT level above three norms is combined with an increase in total bilirubin levels above two norms for some time after starting the drug. FDA position (2000) regarding the hepatotoxicity of statins: an increase in ALT of more than 10 norms distinguishes hepatotoxicity from transaminitis.

Frequency and risk. Clinically significant hepatotoxicity associated with statins? extremely rare side effect. Researchers of the problem believe that if there are signs of liver damage in patients receiving statins, other causes should be looked for: patients treated with statins who have elevated ALT levels of more than 10 normal levels often have associated lesions or are simultaneously taking other drugs that interact with statins or may induce hepatotoxicity. According to a meta-analysis based on MedLine/EMBASE and the Cochrane Collaboration (18 studies, 36,061 patients; 301,062 person-years), serious side effects of statins are comparable to placebo.

Nature and mechanisms of liver damage. The literature describes cases of liver damage of both hepatocellular and cholestatic, as well as mixed types. The mechanism of liver damage is idiosyncratic (immunoallergic reactions).

Serious side effects and risk of acute liver failure. Of particular importance are the serious side effects of statins, primarily acute renal failure, the incidence of which and its association with statin use are constantly monitored. Acute liver failure is a general term for rapidly developing dysfunction of the synthetic capacity of the liver, combined with severe coagulopathy (decrease in PTI or increase in INR), caused by a sharp decrease in the mass of functioning hepatocytes. Severe acute renal failure is combined with hepatic encephalopathy. Mortality without liver transplantation is 80%.

Rare cases of AKI have been reported in response to all cholesterol-lowering medications. A meta-analysis using MedLine/EMBASE data from the Cochrane Collaboration, including 18 studies (36,061 patients; 301,062 person-years), found that serious side effects of statins were comparable to placebo (M.A. Silva et al., 2006). According to K.G. Tolman, for lovastatin, the incidence of AKI is 1 per 1.14 million patient-years, which is at the level of the incidence of idiopathic AKI. L.A. Garcia-Rodriguez et al. (2008) when assessing the incidence of AKI in 100 thousand users of rosuvastatin at the level of primary care in the UK, they found the frequency of AKI, which is associated with taking rosuvastatin, equal to 0.4 (95% CI 0.2-1.0) per 10 thousand. man-years.

The US Adverse Event Reporting System database has reported one case of AKI per million statin prescriptions since 1999. However, the same prevalence of AKI has been reported in individuals not taking statins. According to The National Lipid Association Statin Safety, an expert panel of hepatologists who assessed the side effects of statins was unable to establish an association between changes in laboratory liver tests and cases of development of fully confirmed AKI. The experts concluded that 1) when using statins, acute renal failure develops very rarely, but there is a very low risk of developing this complication when taking any statin, 2) however, an increase in transaminases, including with high doses of statins, is not clearly associated with hepatitis or acute renal failure, 3) in cases of elevated liver enzymes on the background of statins, progression to hepatitis or acute renal failure was not observed.

Drug interactions

In everyday clinical practice, statins are very often prescribed together with other drugs, especially in older people, who usually take several drugs from different groups, which, due to the characteristics of their hepatic metabolism, raises the problem of drug interactions. Side effects of drugs can result from induction (decreased therapeutic effect) or inhibition of elimination (increased toxicity due to excess effect) of drugs.

According to the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (USA), while statins are generally safe, mild and transient adverse reactions are more often observed when they are used together with other drugs metabolized by cytochrome P450 enzymes. Plasma concentrations and the risk of statin toxicity, especially myotoxicity, are significantly increased by strong CYP3A4 inhibitors. Strong inhibitors of CYP3A4 are systemic azole antifungals (itraconazole, ketoconazole, nefazadone), clarithromycin, erythromycin, ritonavir. When co-administered with CYP3A4-dependent statins, drug interactions are possible. Weak or moderate CYP3A4 inhibitors (verapamil, diltiazem) may be used with caution with low doses of CYP3A4-dependent statins.

In terms of drug safety, attention is paid to the problem of combined use of thienoperidines, primarily clopidogrel, and statins. Clopidogrel is a prodrug that requires hepatic biotransformation to its active form in a two-step process dependent on the enzymes CYP2C19 and CYP3A4. However, researchers do not see sufficient reasons to stop the combined use of clopidogrel and statins. Statins may increase concentrations of warfarin and digoxin, which requires clinical monitoring.

Statins compete with other drugs for liver transport systems. Thus, cyclosporine, as well as rifampicin, are transported through the OATP1B1 transporter, which is the mechanism of drug interaction with statins and increasing the risk of their toxicity.

In addition to medications, statins may interact with food components. Grapefruit juice contains flavonoids and furocoumarin derivatives (naringenin and bergamottin), which through cytochrome P450 enzymes can inhibit the metabolism of drugs, including statins. Interaction with statins is possible when drinking more than a liter of grapefruit juice per day.

Consumption of orange bitter may also increase the risk of statin side effects due to similar mechanisms. Due to its bitter taste, Orange bitter is not suitable for consumption as a fruit, but is included as a component of food supplements intended for weight loss and correction of various symptoms (nausea, constipation, etc.), and is also used in cooking in different countries (alcoholic drinks and cocktails, marinades).

Safety of statins in patients with elevated transaminases

Prescribing statins to patients with dyslipidemia, elevated liver enzymes or established liver disease is a dilemma. Meanwhile, in practice, an increase in transaminase levels is often observed, and with rare exceptions, the causes of this are liver diseases: alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), chronic HCV and HBV infections, as well as other less frequent ones. The results of three large studies of the risk of statin use in patients with basal elevated liver enzyme levels without taking into account the nature of the liver disease are known (Table 2).

Table 2. Results of a study of statin use at baseline elevated levels transaminases

According to the data obtained, the risk of hepatotoxicity when prescribed statins in patients with elevated basal transaminase levels did not increase. The incidence of side effects was low and did not exceed that in patients with normal enzyme levels.

Chronic diffuse liver diseases. It is believed that in diffuse liver diseases, the metabolism of statins is impaired. Patients with acute liver diseases of viral, alcoholic or other etiologies do not receive statins until liver enzymes normalize. Experience is accumulating in the use of statins against the background of chronic diffuse liver diseases (CDLD) of various etiologies. So, A.L. Avins et al. (2008) in a retrospective cohort study of 93,106 patients with laboratory or clinical criteria for HDD showed that lovastatin was not associated with an increased risk of adverse hepatic complications. The study did not confirm lovastatin-associated hepatotoxicity in patients with pre-existing liver disease. A multicenter randomized controlled trial involving 326 patients with HDLD with hypercholesterolemia (chronic HCV infection, NAFLD) examined the efficacy and safety of high-dose pravastatin (80 mg/day) for 36 weeks with follow-up at 4, 8, 12, 24 and 36 weeks. weeks They have been shown to be safe and well tolerated. According to K. Gibson et al. (2005), M. Segarra-Newnham et al. (2007), in patients with viral hepatitis C, no significant increase in liver enzymes was recorded during the use of statins of varying durations. C.M. Stanca et al. (2008) when prescribing atorvastatin to patients with primary biliary cirrhosis (PBC) did not reveal a deterioration in laboratory liver tests and the Mayo index. S. Tandra and R. Vuppalanchi (2009), based on expert opinion on the safety of statins, stated that statins are generally well tolerated by patients with CDPD. At the same time, “Information for specialists about the drug Liprimar” (Pfizer) contains information that in patients with alcoholic cirrhosis of the liver (LC) (class B), the concentration of atorvastatin in plasma increases significantly: the maximum concentration (C max) is 16 times , area under the curve (AUC) - 11 times. Researchers emphasize the importance of weighing the benefits and risks of statins for liver disease. According to experts assessing the side effects of statins on the liver, The National Lipid Association Statin Safety, the use of statins is safe in patients with compensated cirrhosis, non-alcoholic steatosis and steatohepatitis. Other experts share the same point of view. Thus, G. Anfossi et al. (2004) based on the study, they concluded that patients with chronic hepatitis can receive statins if the risk of cardiovascular disease is increased and liver function control is possible.

B Safety of statins in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of characteristic liver changes predominantly with coarse steatosis in individuals who have not consumed alcohol in quantities that cause liver damage. Although there are many known causes of hepatic steatosis, NAFLD is mainly associated with insulin resistance (IR) and metabolic syndrome (MS), which has given rise to consider NAFLD as a hepatic manifestation of MetS. NAFLD occupies an important place in clinical medicine as an extremely common pathology. Patients with NAFLD are typical candidates for statins. The problem of the safety of statins against the background of existing NAFLD is extremely relevant in terms of the admissibility of their use for the prevention of cardiovascular diseases when comparing benefits and risks, although positive effects on the liver are also being studied in the process of their use.

During the study of the use of statins in NAFLD, an evolution of views occurred: stage I - statins can have a negative effect on the liver, stage II - statins are quite safe and their use is acceptable, stage III - statins are useful and necessary for the liver.

The negative position is based on the identified properties of statins to increase the hepatic expression of LDL receptors and lipogenesis in the liver, which may cause increased fatty infiltration of the liver.

The neutral position is based on the results of studies of the use of statins in patients with NAFLD - both steatosis and non-alcoholic steatohepatitis (NASH), which occurs with elevated levels of liver enzymes. The researchers found no significant differences in enzyme levels compared to placebo. Thus, according to P. Riley et al. (2008), in patients with NAFLD during treatment with statins, an increase in ALT > 40 U/L was noted in 15.4% of cases, was transient and returned to normal after a break in treatment. The results of a study of the effect of statins on the morphological picture of the liver were obtained: M. Ekstedt et al. (2007) when comparing the morphological picture of the liver before and after 10.3-16.3 years of treatment compared to the control group (without statins), they did not note progression of fibrosis. R. Vuppalanchi and N. Chalasani (2006) concluded that fluctuations in liver enzymes may be a manifestation of the natural progression of liver disease, and not a statin-related effect.

A positive attitude is in its infancy and is based on the results of experimental and clinical studies. In experiments, the use of statins in animals with IR led to the suppression of VLDL hyperproduction and an increase in insulin sensitivity, a decrease in steatosis, inflammation and damage to hepatocytes in NAFLD. Clinical studies in NAFLD have established the ability of statins to reduce the production of IL-6-induced C-reactive protein in hepatocytes and reduce the serum concentration of carbohydrate metabolism products. H.A. Wiesinger et al. (2008) in patients with NAFLD and NASH with elevated AST levels (> 60 U/L), the administration of statins even led to normalization of AST activity and was safe. E. Gomez-Dominguez et al. (2006) reports positive experience with the use of atorvastatin in doses from 10 to 80 mg/day, which contributed to the normalization of transaminase levels. The results of a randomized controlled trial of the use of atorvastatin at a dose of 20 mg/day for 12 months are known. (V.G. Athyros al., 2006) - an improvement in ultrasound parameters of the liver was found in NAFLD.

The results obtained indicate the effectiveness and safety of statins in NASH. According to G. Anfossi et al. (2004), the positive effect of statins overcomes the risk of side effects in NASH accompanied by dyslipidemia in patients with IR. The Asia-Pacific Working Party on NAFLD outlined general approaches to the treatment of NAFLD, and statins were considered safe and recommended, and frequent ALT monitoring was not required. The latest largest study of atorvastatin included patients with NAFLD ( GREACE, 2010), led to the following conclusions: 1) statins improved laboratory parameters in patients with NAFLD, 2) the effect of statins was more pronounced in patients with abnormal tests, and 3) most noticeable in individuals with alcohol and other etiological factors of liver disease were excluded.

Summarizing the results of the analysis of all points of view and arguments in their favor, and also taking into account the known role of NAFLD as a risk factor for cardiovascular diseases and the need of patients for drugs that lower lipid levels, the following position may be relevant:

· Patients requiring statins often have NAFLD;

· Statins predominantly do not have negative effects on the liver in patients with NAFLD;

· side effects of statins are rare;

· statins have effects that reduce IR;

· Statins have a beneficial effect on the structure and function of the liver in NAFLD.

However, statins for the treatment of NAFLD itself, including NASH, have not yet received routine distribution in clinical practice.

Statins for liver diseases with secondary hyperlipidemia

Secondary hyperlipidemia is typical of cholestatic liver diseases, including primary biliary cirrhosis (PBC). Such hyperlipidemia is clinically significant, according to C.M. Stanca et al. (2008), about 12% of patients with PBC die from cardiovascular diseases, which makes the problem of correcting hyperlipidemia relevant. In case of toxic liver damage from alcohol-containing liquids (cases of which occurred in Belarus in 2006-2007) occurring with intrahepatic cholestasis, the cholesterol level in most cases was 12-15 mmol/l, and in some cases reached 30-32 mmol/l.

The results of two small studies of the use of simvastatin for the correction of hyperlipidemia in PBC showed a reduction in cholesterol levels, the safety of treatment, and even a decrease in the activity of laboratory markers of cholestasis (ALP, GGTP). T. Stojakovic et al. (2007) in patients with PBC with an incomplete biochemical response to ursodeoxycholic acid, they established a positive effect of statins in reducing cholesterol without affecting cholestasis.

Another clinical situation is immunosuppressive therapy-induced hypercholesterolemia, which is a common complication after liver, as well as kidney and heart transplantation. The safety of using statins under the control of liver tests for the correction of hyperlipidemia in this category of patients has been shown. Thus, in patients after liver transplantation with post-transplant hyperlipidemia who received immunosuppressants (cyclosporine, tacrolimus or sirolimus), with the addition of statins, no side effects were found in the liver and no changes in the pharmacokinetics of cyclosporine. W. Lisik et al. (2007), based on a retrospective study of 325 patients after kidney transplantation, report a five-fold increase in liver enzymes in 3.4% of patients (statins were discontinued), a three-fold increase in 3.0% (statins continued). Such studies convincingly demonstrate the safety of statins in the context of drug interactions.

However, despite the data obtained on the increase in the number of cardiovascular complications in secondary hypercholesterolemia and some positive results of the use of statins in cholestatic liver diseases, secondary hypercholesterolemia itself without the presence of other risk factors does not require specific intervention, and the use of statins for its correction is not a rule.

Safety of statins in selected patient groups

The safety of statins is specifically discussed in relation to children and elderly people. In elderly and senile patients, statins are prescribed less frequently due to the risk of side effects. The TNT study focuses on the use of statins in this age group ( n= 2847). A low frequency of side effects when taking low doses - 5.2%, high doses - 8.3%, comparable with the study results obtained by the authors in other groups, was shown; the frequency of drug withdrawal when taking low doses is 2.2%, high doses are 4.4%; frequency of persistence (1-4 days) of elevated levels of transaminases (more than three norms) when taking 10 mg/day - 1.3% (n=24), high - 0.1% ( n= 1) . A retrospective analysis of 50 randomized clinical trials (5924 patients over 65 years of age) showed the frequency of persistence of elevated transaminase levels more than 3 times, the presence of side effects while taking atorvastatin in doses of 10, 20, 40 and 80 mg/day 0.1%, 0%, 0.2%, 0.5%, respectively, in the placebo group - 0.2% and a similar frequency of drug withdrawal. Serious side effects were reported in 1%.

Positive effects of statins on the liver

In recent years, experimental and clinical evidence of the beneficial effects of statins on the liver has emerged (a summary of the evidence is given in Table 3).

Table 3. Type of research, literature sources

However, large studies with morphological control are required to judge the benefits of statins in patients with HDD.

Monitoring for hepatotoxicity

Along with controlled studies of the safety of statins, vast experience in their practical use has already been accumulated; special cohort studies have been conducted to monitor treatment, which is of great importance, since the drug has been received by a huge number of patients, including those with risk factors, concomitant diseases, and taking other drugs. As a result of studies of monitoring the hepatotoxicity of statins, it was shown that over a period of 6 to 42 months, deviations in at least one liver test were observed in 0.3-1.0% of patients (Table 4).

Table 4. Results of monitoring hepatotoxicity of statins

Researchers are of the opinion that there is no need for routine monitoring of laboratory liver tests. K.G. Tolman et al. (2002) examined the results of routine aminotransferase screening in primary care using computerized medical records (Boston, USA). All patients who received statins in 1998 were identified (1194 people, 1014 had laboratory tests examined at least once). In 1.0% of patients there was a significant increase in transaminases and in 0.5% there was a moderate increase, but in no case could it be reliably associated with taking statins. These data call into question the validity of routine transaminase testing in statin users: routine monitoring is not considered an effective approach to preventing serious liver injury, including AKI, primarily due to its extreme rarity and poor predictive value of minimal ALT elevations. J. Armitage (2007) suggests that routine monitoring of liver function after initiation of treatment is not recommended for simvastatin, pravastatin and lovastatin at doses up to 40 mg/day, but is recommended for other statins and for high doses of any statins.

There are various recommendations regarding baseline testing and monitoring of liver enzymes during statin treatment. They change and are not based on clinical practice data. Thus, the FDA requires instructions for use of statins to require liver tests before initiation and at intervals that vary depending on the drug during treatment. According to the American College of Physicians guidelines on lipid monitoring in patients with type 2 diabetes treated with statins, routine monitoring of liver function tests is not recommended except in special situations.

The National Lipid Association's Statin Assessment Task Force (USA, 2005), based on an analysis of the widespread use of statins, considers that side effects do not require routine liver monitoring, but are recommended in patients with existing symptoms of liver damage. From the point of view of an expert group of hepatologists, a more sensitive tactic for assessing manifestations of liver toxicity in people taking statins should be considered not periodic assessment of transaminases, but continuous monitoring of clinically significant symptoms of liver dysfunction, including jaundice, general malaise, increased fatigue and drowsiness , and when such symptoms appear, a study of bilirubin fractions, which turned out to be the most informative biochemical indicator for identifying clinically significant liver damage compared to an isolated increase in transaminase levels.

1. During routine general examination of patients, including those already taking statins, it is advisable to assess the level of hepatic transaminases. If abnormal test results are obtained, further testing may be necessary to determine the cause of the results.

2. Until the FDA-approved information for statins is changed, it is considered appropriate to continue measuring transaminase levels before starting treatment, 12 weeks after starting treatment, after dosage increases, and periodically thereafter. However, the need for periodic assessment of biochemical parameters of liver function has not been proven and there is a need to change existing FDA recommendations.

3. Clinicians should be wary of patients taking statins reporting jaundice, malaise, fatigue, drowsiness, and related symptoms, which may indicate possible liver toxicity. Manifestations of liver toxicity include jaundice, liver enlargement, increased indirect bilirubin levels, and increased prothrombin time (to a greater extent than just increased liver transaminases).

4. The most informative biochemical indicator for identifying clinically significant liver damage is considered to be the assessment of bilirubin fractions, which, in the absence of biliary tract obstruction, serve as a more accurate prognostic factor of liver damage compared to an isolated increase in transaminase levels.

5. If a doctor detects signs of clinically significant liver damage in patients using statins, therapy with them should be discontinued. Attempts should be made to determine the cause of liver damage, and if indicated, the patient should be referred for consultation to a gastroenterologist or hepatologist

6. With an isolated increase in transaminase levels by 1-3 times compared to the upper limit of normal in the absence of clinical manifestations, there is no need to stop taking statins.

7. If there is an isolated increase in transaminase levels of more than 3 times the upper limit of normal during a routine examination of a patient prescribed statins, the analysis should be repeated, and if elevated levels of liver enzymes persist, another cause of such an increase should be excluded. In this case, depending on the clinical data, the possibility of continuing to take the statin, reducing its dose or stopping treatment should be considered.

8. According to experts assessing the side effects of statins on the liver, the use of statins is safe in patients with compensated cirrhosis of the liver, chronic liver disease, fatty hepatosis of non-alcoholic origin or non-alcoholic steatohepatitis.

Analysis of the literature data regarding the safety of statins suggests that hepatotoxicity is rare, and attention focused on the increase in trans-aminase levels with statins is inadequate. Confident knowledge of information in the field of this problem allows the doctor in each specific case to compare the benefits and risks of using statins and, if there are compelling reasons for treatment, to make the right choice without false alarms.

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Attention!The article is addressed to medical specialists. Reprinting this article or its fragments on the Internet without a hyperlink to the source is considered a violation of copyright.

For the liver? This question interests many patients. In the modern world, due to the fast pace of life, we often do not have time to have a good lunch or breakfast. The functioning of the liver is disrupted by unhealthy foods and other factors. How to protect the liver from all adverse factors?

More recently, drugs of the statin class were invented to treat high cholesterol. Their beneficial properties are expressed as follows:

• block the production of enzymes involved in the synthesis of harmful organic compounds;
• cleanse blood vessels;
• reduce the risk of developing heart disease.

But like any other drugs, statins for the liver can cause side effects, so the choice of drug must be approached as carefully as possible.

Modern drugs

Today, the most effective and safe are Atorvastatin and Rosuvastatin.

Medicines affect lipid metabolism in our body and reduce the daily toxic poisoning that we get from breathing dirty air in a big city.

According to various clinical studies, the most effective and safe drug is Atorvastatin. In addition to lowering cholesterol levels, the medicine reduces the risk of blood clots, thereby preventing myocardial infarction. Also, according to statistics, thanks to the drug, the mortality rate of patients over 75 years of age is reduced.

It follows from this that this representative of a new generation of drugs is recommended not only for the treatment of atherosclerosis, but also for the prevention of cardiovascular diseases among people aged 50 years and older.

However, it is worth noting that the lipid profile in the body normalizes within 2 to 4 months, so the drug should be taken for quite a long time.

Rosuvastatin ranks 2nd among the safest drugs against high cholesterol. Its main advantage is the effective prevention of plaque on blood vessels. The period of taking the medicine varies from 1 to 2 months.

Simvastatin also belongs to a group of drugs that help fight atherosclerosis. This product can be used for a long period without fear for your health.

Liver protection

To date, the impact of statins is controversial. When using medications, the risk of complications that can accompany atherosclerosis is prevented.

According to some experts, when taking statins, there is a possibility of developing myopathy. This is due to the fact that the muscles in our body need a small amount of cholesterol. The development of oncological diseases (liver cancer) is also possible.

How to protect such an important organ from side effects that drugs can cause? Firstly, along with medications, you can take coenzyme Q10. This substance promotes energy production, prevents the formation of blood clots, and lowers blood pressure.

The main disadvantage of statins is that although the drugs destroy cholesterol in our body, they also deplete the supply of coenzyme Q10, which is contained in every cell of our body. Side effects:

• muscle pain appears;
• memory deteriorates;
• Chronic fatigue and lethargy overtakes.

To prevent these side effects, patients need to take medications that contain the necessary microelements.

Liver protection from statins should be provided. To do this, the patient should refrain from taking painkillers.

The fact is that Ibuprofen and other similar drugs create additional stress on many organs, which is why atherosclerosis can become more severe.