Chapter 38 Glandular Therapy
Methods of Manufacture of Glandular Preparations
Evidence for Intact Protein Absorption
For almost as long as historic records have been kept, glandular therapy has been an important form of medicine. The basic concept underlying the medicinal use of glandular substances from animals is that “like heals like.” For example, if the liver needs support or a patient is suffering from liver disease, then he or she may benefit from eating beef liver. Modern glandular therapy, however, primarily involves the use of concentrated glandular extracts.
A gland is defined as a secretory organ. The internal secretory organs of the body are called endocrine glands. These ductless glands secrete hormones directly into the bloodstream. The glands known to have endocrine function include the pineal, pituitary, thyroid, parathyroid, thymus, adrenal, pancreas, and gonads (testes or ovaries). Although not technically glands, it is common to refer to other organs of the body as glandulars when they are used in glandular therapy. For example, tissue extracts of heart, spleen, prostate, uterus, brain, and other tissues are often used in glandular or organotherapy.
Research has shown that certain glandular preparations and hormones are quite effective when taken orally. A number of glandular preparations are effective orally because of active hormone or enzyme content (e.g., thyroid, adrenal cortex, and pancreatin preparations). A good deal of literature supports pharmaceutical grade liver, aorta, and thymus extracts, and some support exists for pituitary, spleen, orchic (testes), and ovarian extracts as well. However, despite this scientific support, many still question the effectiveness of glandular products on human health.
A key challenge to the use of glandulars is the lack of widely accepted standards for extraction and quantification. Each manufacturer of a glandular product claims its method of extraction is the most ideal. However, the majority of these contentions are based on theoretic or philosophic grounds, not on research or clinical results. No quality control procedures or standards are enforced in the glandular industry. It is left up to the individual company to adopt quality control and good manufacturing procedures. Nonetheless, many glandular preparations available in the U.S. marketplace appear to be effective.
Methods of Manufacture of Glandular Preparations
It is critical that properly processed glandular material be used, since the biologically active material such as enzymes, soluble proteins, natural lipid factors, vitamins, minerals, and hormone precursors are destroyed or eliminated if the product is not prepared properly.
Most glandular products are derived from beef (bovine) sources, the exception being pancreatic extracts, which are most often derived from pork (porcine) sources. The four most widely known methods of processing are the azeotrophic method, salt precipitation, freeze-drying, and predigestion.
The Azeotrophic Method
The azeotrophic method begins by quick freezing the material at well below 0°F, and then washing the material with a solvent (such as ethylene dichloride) to remove the fatty tissue. The solvent is then distilled off, and the material is dried and ground into a powder so that it can be placed in tablets or capsules. Although the azeotrophic method eliminates the problem of fat-stored toxins like pesticides and healthy metals, unfortunately, it also removes fat-soluble hormones, enzymes, essential fatty acids, and other potentially beneficial materials; in addition, traces of the solvent still remain.
The Salt Precipitation Method
This method involves the maceration of fresh glandular material in salt and water. Because the salt increases the density of the water-soluble material, when the mixture is centrifuged, the lighter fat-soluble material can be separated out. The material is then dried and powdered. The benefit with the salt precipitation method is that no toxic solvents are used to separate the fatty material. The downside is the increased salt content of the product.
The freeze-drying process involves quickly freezing the glandular material at temperatures of −40°F to −60°F and then placing the material into a vacuum chamber, which removes the water by direct vaporization from its frozen state (hence, the term freeze-drying). The benefit of freeze-drying is that it contains a higher concentration of unaltered protein and enzymes, as well as all of the fat-soluble components. Because the fat is not removed, it is critical that the glands are derived from livestock that have grazed on open ranges not sprayed with pesticides or herbicides. The animals must also be free from antibiotics, synthetic hormones, and infection.
The predigestion method employs plant and animal enzymes or some other method to partially digest or hydrolyze the glandular material. The partially digested material is then passed through a series of filtrations to separate out fat-soluble and large molecules. The purified material is then freeze-dried. This method of extraction is best for glandulars (such as the liver and thymus) where the polypeptide and other water-soluble fractions are desired.
Bovine spongiform encephalopathy (BSE), also known as mad cow disease, is a transmissible, slowly progressive, degenerative, fatal disease affecting the central nervous system of adult cattle. The transmissible agent in BSE is a modified form of a normal cell surface component known as a prion protein. Unlike infectious organisms, prions are resistant to common treatments, such as heat and digestive secretions. Eating the meat of an animal with BSE may lead to a disease similar to BSE in humans called variant Creutzfeldt-Jakob disease.
BSE was first reported among cattle in the United Kingdom in 1986 and has been a major concern since then. The outbreak in the United Kingdom may have started from the feeding of scrapie-contaminated sheep meat-and-bone meal to cattle. Scrapie is a disease of sheep that is related to BSE in cattle. Evidence is strong that the outbreak in cattle was amplified in the United Kingdom by feeding rendered bovine meat-and-bone meal to young calves.
BSE has been reported in cattle throughout Europe. There has been a single case in Canada and, most recently, in the United States from a cow imported from Canada. Wild game in the United States such as deer and elk have been affected with a similar disease known as chronic wasting disease. The reason American cattle have been spared may be due to the active surveillance and import measures taken by the U.S. Food and Drug Administration (FDA) and the U.S. Department of Agriculture (USDA).
The USDA has restricted the importation of live ruminants, such as cows and sheep, and food products from these animals from BSE countries since 1989, and from all European countries since 1997. In addition, the FDA prohibits the use of most mammalian protein in the manufacture of animal feeds given to ruminants because this kind of feeding practice is believed to have initiated and amplified the outbreak of BSE in the United Kingdom.
To reduce the risk of ingesting beef with BSE, it is critical to use products manufactured under the following guidelines:
• The June 2000 European Commission Decision regulating the use of material presenting risks for BSE
• A “Certification of Suitability” by the European Directorate of Quality of Medicines to ensure the highest quality, pharmaceutic grade material is being used
• The FDA’s guidelines for sourcing and processing of bovine material
Evidence for Intact Protein Absorption
There is now considerable evidence that large macromolecules pass intact from the normal human gut into the bloodstream. In some instances, the body appears to recognize which molecules it needs to absorb intact and which molecules it needs to break down into smaller units. This phenomenon may help to explain the effectiveness of glandular therapy.
Numerous whole proteins have been shown in human and animal studies to be absorbed intact into the bloodstream after oral administration.1–7 These include human albumin and lactalbumin, bovine albumin, ovalbumin, lactoglobulin, ferritin (molecular weight 500,000), chymotrypsinogen, elastase, and other large molecules.
Furthermore, proteins and polypeptides, as well as various hormones that are absorbed intact from the gut, have been shown to exert effects in target tissues. For example, in addition to thyroxine or thyroid hormone and cortisone, several peptide hormones are known to be biologically active when administered orally, including luteinizing hormone-releasing factor and thyrotropin-releasing hormone.8,9 Even insulin has been shown to be absorbed orally under certain circumstances (e.g., in the presence of protease inhibitors or hypertonic solutions in the intestines).10,11
These data indicate that at least some of the larger molecules in glandular products are absorbed intact to induce physiologic effects, particularly polypeptides, which exert hormone or hormone-like action.
An adequate body of research now exists to support the use of orally administered glandular extracts. The following is a brief discussion of several glandular preparations and their use. Table 38-1 lists the primary conditions responding to glandular therapy.
|Adrenal extracts||Chronic fatigue|
|Aortic glycosaminoglycans||Cerebral and peripheral arterial insufficiency|
Venous insufficiency and varicose veins
Vascular retinopathies, including macular degeneration
|Liver extracts||Chronic hepatitis|
Chronic liver disease
|Pancreatic extracts||Pancreatic insufficiency|
Inflammatory and autoimmune diseases such as rheumatoid arthritis, scleroderma, athletic injuries, and tendinitis
|Spleen extracts||After splenectomy|
Systemic lupus erythematosus
Low white cell counts
|Thymus extracts||Recurrent and chronic viral infections, such as chronic fatigue syndrome, respiratory infections, AIDS, acute hepatitis B infection|
Cancer patients with immune depression from chemotherapy or radiation
Asthma, hay fever, eczema, and food allergies
Autoimmune disorders, such as rheumatoid arthritis, lupus erythematosus, and scleroderma
AIDS, acquired immunodeficiency syndrome.
Oral adrenal extracts have been used in medicine since at least 1931.12 Adrenal extracts may be made from the whole adrenal gland or just from the adrenal cortex. Whole adrenal extracts (usually in combination with essential nutrients for the adrenal gland) are most often used in cases of low adrenal function, presenting as fatigue, inability to cope with stress, and reduced resistance. Because extracts made from the adrenal cortex contain small amounts of corticosteroids, they are typically used as a “natural” cortisone in severe cases of allergy and inflammation (e.g., asthma, eczema, psoriasis, rheumatoid arthritis).
The dosage of adrenal extract depends on the quality and potency of the product. The best measure of an effective dose for a preparation may be the level of stimulation (irritability, restlessness, and insomnia) the patient experiences. When prescribing adrenal extracts, start at one third of the recommended dosage on the label and slowly increase the dosage every 2 days until a stimulatory effect is noted. Once this effect is noticed, reduce the dosage to a level just below the level that produces stimulation.
A mixture of highly purified bovine-derived glycosaminoglycans (GAGs) are naturally present in the aorta, including dermatan sulfate, heparan sulfate, hyaluronic acid, and chondroitin sulfate; related hexosaminoglycans have been shown to protect and promote normal artery and vein function. More than 50 clinical studies have shown an orally administered complex of aortic GAGs to be effective in a number of vascular disorders, including the following:
• Cerebral and peripheral arterial insufficiency
• Venous insufficiency and varicose veins
• Vascular retinopathies, including macular degeneration postsurgical edema13–22
Significant improvements in both symptoms and blood flow have been noted.
In addition, aortic GAGs have many important effects that interfere with the progression of atherosclerosis, including prevention of damage to the surface of the artery, formation of damaging blood clots, migration of smooth muscle cells into the intima, and formation of fat and cholesterol deposits, as well as lowering total cholesterol levels while raising high-density lipoprotein cholesterol.23–27
Beef (bovine) liver extracts and concentrates are a rich natural source of many vitamins and minerals, including iron. Liver extracts can contain as much as 3 to 4 mg of heme iron per gram. In addition to its use as a source of iron and other nutrients, hydrolyzed liver extracts have been used to treat chronic liver diseases since 1896. Numerous scientific investigations into the therapeutic efficacy of liver extracts demonstrated that these extracts improved fat utilization, promoted tissue regeneration, and prevented damage to the liver.29–32 In short, clinical studies demonstrated that oral administration of hydrolyzed liver extracts can be quite effective in improving liver function.
For example, in one double-blind study, 556 patients with chronic hepatitis were given either 70 mg of liver hydrolysate or a placebo three times daily.32 After 3 months of treatment, the group that received the liver extract had far lower serum liver enzyme levels. Because the level of liver enzymes in the blood reflects damage to the liver, it can be concluded that liver extract is effective in chronic hepatitis via an ability to improve the function of damaged liver cells, as well as prevent further damage to the liver.
The dosage is entirely dependent on the concentration, method of preparation, and quality of the liver extract. The highest quality products are aqueous hydrolyzed extracts because they have the fat-soluble components removed and typically contain more than 20 times the nutritional content of raw liver, including 3 to 4 mg of heme iron per gram.