Update on Development of Integrase Inhibitors
There is a tremendous amount of interest in integrase inhibitors following the recent articles in the medical literature. A research group at Merck has highlighted the difficulty in developing a test to truly screen for compounds that inhibit HIV integrase, an enzyme essential for HIV to reproduce. They are developing several lead compounds, and hopefully one of these will lead to a drug that inhibits HIV integrase.
Another class of compounds that have generated some interest is chicoric acid, which comes from chicory and is a chemical extract from green coffee beans. Chicoric acid itself is not potent enough to work as an anti-HIV integrase drug, and so research is ongoing to develop derivatives of chicoric acid that are more potent.
Toward a Healthy Liver
Your liver, the largest organ in the body, is located behind the lower ribs on the right side of your abdomen and is roughly the size of a football. The liver performs critical functions in your body, like filtering blood, eliminating toxins, and producing factors that help blood clot. It processes many drugs into forms that are easier for the body to use. It also converts sugar into triglycerides (lipids/fats) and glycogen (a form of glucose/sugar stored by the liver) that helps regulate the body's need.
The work of the liver is critical to the brain and central nervous system. These tissues receive their energy supply only from sugar, so they are vulnerable when the liver is damaged and unable to supply and regulate chemicals in the body.
The liver helps you by:
- Producing quick energy when it's needed;
- Making new proteins;
- Storing certain vitamins, minerals (including iron), and sugars to prevent shortages of body fuel;
- Regulating transport of fat stores;
- Controlling blood clotting;
- Aiding digestion by producing bile (which helps your system break down food);
- Controlling the production and elimination of cholesterol;
- Neutralizing and destroying poisonous substances;
- Processing alcohol;
- Cleansing the blood and getting rid of waste products;
- Maintaining hormone balance; and
- Helping the body resist infection.
Many people with liver disease, or people who take medications that affect liver function, seek information on nutritional and complementary ways to promote liver health. Some commonly used over-the-counter pain relievers can be hard on the liver if used too frequently. There are also a number of prescription drugs, including those used to treat HIV disease, that can stress the liver. There are nutritional/dietary changes that people can make that may go a long way in helping the liver.
There are a number of available, although unproven, supplements that may help promote liver health. As individuals explore these supplements, it's important to keep in mind that their use has not been proven to be beneficial. This doesn't mean that they are not useful, but rather that the research hasn't been conducted to determine whether or not they are beneficial.
Deciding whether or not to use supplements and herbs to promote liver health unfortunately must be done without conclusive data from well-designed and controlled studies to inform wise decision-making. A few supplements, believed by some nutritionists and many supplement promoters to improve liver health, are found later in this paper. Moreover, a list of herbs -- compiled by the HCV Advocate -- that are known or believed to be toxic to the liver are provided. Included is also a list of herbs that may be safe for the liver, though their health benefits remain unproven.
There are many things you can do to help your liver and keep it healthy! The first is to reduce the work load of the liver. Simple changes in your diet can go a long way in helping. Since the liver converts and detoxifies everything we eat and drink, a well-balanced nutritious diet is a good start. The following are some dietary suggestions that may help:
- Flush your system by drinking eight glasses of water a day.
- Consider a low-fat, low-sodium, and high-fiber diet. Avoid over-eating high fat foods like fried foods, french fries, and most fast-food items. Poor quality processed foods like canned or frozen foods and processed meats and cheeses sometimes contain little fiber or reduced nutrients. They are often high in salt and should be avoided. But there are no hard and fast rules here. High quality, well-preserved foods and frozen goods can also be very high in nutritional value if proper care is taken.
- Familiarize yourself with the ingredients and contents of the foods you buy. If possible, eat the highest quality fruit and vegetables you can find, and even these, whether organic or commercial, should be carefully washed before using.
- Be careful with any food if you don't know its source. For example, some innocent-looking wild mushrooms can destroy a person's liver in a matter of days.
- Maintaining adequate protein intake and body weight is essential. If your liver is damaged, reduce salt in your diet. Meats tend to be high in salt. Try to eat vegetables that are high in protein. Animal source proteins include meat, fish, eggs, poultry, and dairy products. Lean meat is best. Trim fat off red meat and remove the skin from poultry.
- Do not eat raw or scavenger fish (catfish, etc.). They may contain chemicals and bacteria that are harmful to the liver. People with liver problems should be especially cautious about eating shellfish of any kind, as they can be a source of hepatitis A. Someone with an already damaged or stressed liver doesn't need to fight an additional battle.
- Since the liver maintains glucose levels, essential to brain and nervous system function, small frequent meals are recommended. This helps the liver work less.
Excess iron can damage the liver. If your liver is compromised, some nutritionists believe you should decrease or avoid eating red meats, liver, and iron-fortified cereals. Avoid cooking with iron-coated cookware and utensils. The average diet supplies enough iron to meet the body's needs.
Some over-the-counter medications should be avoided, as should excessive levels of some vitamins. If your liver is seriously compromised, Tylenol and other drugs containing acetaminophen should be avoided. Also, if your liver is seriously compromised, avoid anti-inflammatory non-steroidal drugs like Advil and ibuprofen. Care should be taken to avoid too much vitamin A, as high levels can be toxic to the liver. In general, these types of drugs should be taken for a maximum of five consecutive days, as taking them longer can cause stress and possibly harm the liver. Likewise, aspirin should be taken with care because it can lower platelet counts. People with liver disease often experience swelling of the spleen, which frequently destroys platelets faster than the body can make them. Aspirin will add to this problem.
All benzodiazepines can be harmful to the liver and thus should be used with careful monitoring of liver function. These include diazepam (Valium), temazapam (Restoril), and others. Many prescription drugs, including those to treat HIV disease, can stress the liver. Ritonavir, when used at full dose, presents probably the greatest challenge to the liver. But any drug that is metabolized through the liver can create problems. For a list of side effects associated with commonly-used therapies to treat and manage HIV disease, see Dealing with Drug Side Effects.
Alcohol is among the most severely toxic agents processed by the liver. The American Liver Foundation suggests no more than one drink a day. Total avoidance is recommended for people with liver disease. Many liquid cold and flu medicines contain alcohol and should be used with caution. As a rule, regardless of the type of medication, read the labels and check the ingredients. Speak to your doctor and/or pharmacist about potential problems.
Avoid street drugs. Street drugs often are impure and contain harmful chemicals. They may also have bacteria in them that can make you sick and harm the liver.
Avoid smoking and fumes. Everything we breathe has to be filtered by the liver. It is believed that smoking cigarettes increases the chance of developing liver cancer. Fumes from paint thinners, bug and aerosol sprays, etc., can damage your liver and should be avoided.
Many supplements are thought to help the liver. Perhaps the most researched of these is an herb called milk thistle (the active ingredient of which is known as silymarin). A review of the literature suggests that milk thistle is not harmful, but studies have not yet proven that it is beneficial. A large study is currently enrolling through the Veteran's Administration to assess its effectiveness for people with liver disease.
Some supplements may help promote liver health, though research proving their value has not been conducted. These include vitamin C with bioflavinoids, vitamin E, coenzyme Q-10, and N-Acetyl-Cysteine (NAC). NAC is commonly used to counteract the liver-damaging effects of acetaminophen (Tylenol) overdose. Studies have used doses of 500mg NAC twice daily.
Some caution should be taken with these supplements. Since most have not been studied in combination with anti-HIV drugs, it is not known whether they will affect the drug levels of anti-HIV therapies. Many of these supplements are metabolized (broken down) by the same enzymes used by anti-HIV therapies and as a result there is a potential for an interaction.
(The following is excerpted from the HCV Advocate
|Herbs with known liver toxicity:
- Alpine Cranberry (Vaccinium vitis-idaea)
- Mercury Herb (Mercurialis annua)
- Sweet Clover (Melilotus officianalis)
- Trailing Arbutus (Epigae repens)
- Woodruff (Galium odorata)
- Schissandra chinensis
- Tonka Beans (Dipteryx odorata)
- Witch Hazel (Hamamelis virginiana)
- Kinnik-kinnik or Bear berry (Arctostaphylos uva-ursi)
Herbs to avoid -- with possible liver toxicity:
- Plants of the Senecio, Crotolaria, and
- Alkanna (Alkanna tinctoria)
- Chaparral (Larrea tridentata)
- Comfrey (Symphytum officinale and S. uplandicum)
- Dusty Miller (Senecio cineraria)
- Forget-Me-Not (Myosotis cineraria)
- Groundsel (Senecio vulgaris)
- Borage (Borago officianalis)
- Colts Foot (Tussilago farfara)
- Dong Quai (Angelica polymorpha)
- Ephedra also known as Ma Huang or Mormon Tea (Ephedra sinica)
- Germander (Teucrium chamaedrys)
- Hemp Agrimony (Eupatorium cannabinum)
- Hops (Humulus lupulus)
- Life Root (Senecio aureus and S. nemorensis)
- Mistletoe (Phoradendron leucarpum and Viscum album)
- Petasites (Petasites hybridus)
- Ragwort (Senecio jacobea)
- Sassafras (Sassafras albidum)
- Yohimbe (Pausinystalia yohimbe)
- Jin Bu Huan (Lycopodium serratum)
- Mormon Tea (Ephedra nevadensis)
- Pennyroyal (Mentha pulegium)
- Pokerroot (Phytolacca americana)
- Rue (Ruta graveolens)
- Skullcap (Scutellaria laterfolia)
Herbs that may be useful and are also considered safe:
- Artichoke (Cynara scolymus)
- Chamomile (Matricaria chamomilla)
- Licorice (Glycyrrhiza glabra) not recommended for long
- Maitake (Grfloa frondosa)
- Peppermint (Mentha piperata)
- Soybean (Glycine soja)
- California Poppy (Escholtzia californica)
- Dandelion (Taraxacum officinale)
- Rosemary (Rosemarinus officinalis)