Glandular therapy is a medical practice with roots in traditional medicine that originate from thousands of years of experience. Also known as organotherapy, tissue therapy, or cell therapy, glandular therapies for pets are characterized by the use of animal tissues to produce biological effects in humans or other animals. Whole animal tissues, organs, or special extracts are used to support, repair, or manage early functional health issues. Organ tissues are utilized to achieve effects on the corresponding organ tissue of the user in hopes of achieving beneficial physiologic changes and healing. In essence, the goal is “like” heals “like.” For example, liver tissue benefits the user’s liver, and adrenal tissue benefits the user’s adrenal glands.
Glandular Therapies in Dogs and Cats
Veterinarians have been using glandular therapies in dogs and cats for decades. Oral freeze-dried concentrates of liver, kidney, heart, thyroid, collagen, bone, spleen, adrenal, pituitary, and other tissues have been used to treat and manage degenerative conditions with some success. This area of veterinary medicine needs further exploration in both laboratory studies and clinical trials to document efficacy.
Some concerns have arisen as to whether whole glandular or live cell therapies might transmit infectious disease including viruses from one species to another. Freeze-drying, however, regulates sterility yet allows preservation of cell materials for a longer time. Use of freeze-dried cell ultrafiltrates also removes potential antigenic cell surface material and allows for better quality control.32 Concerns for transmission of Bovine Spongiform Encephalopathy (BSE) requires only tissues be procured from countries and herds/flocks free of this disease. Humane treatment of animals is also paramount when tissues from one donor species are used to treat another. More research and standardization of glandular therapies is needed to investigate its best application and its potential use in both humans and pets.
Ancient Use of Glandular Therapy
Ancient Egyptian medicine and Ayurvedic writings from several hundred years B.C. mention therapeutic use of animal tissues and glandular materials.1 A 16th century physician named Paracelsus claimed that “like cures like” in a “doctrine of signatures”; or in other words, kidney heals kidney, and liver heals liver.2 Glandular therapies then evolved into what would be considered scientific endocrinology in the 19th century, as it was documented with much enthusiasm the dramatic healing of a patient suffering from severely low thyroid function (myxomatous edema) with a glandular extract of thyroid tissues.3 Glandular therapy then became termed the more rational “organotherapy” as it gained increased acceptance in mainstream medicine. Crude extracts and whole gland concentrates developed in the 1920s and 1930s with more reputable supply companies and an increase in the literature regarding the clinical use of glandular materials.4 Cell therapies also emerged in the mid-twentieth century consisting of injections of fresh animal cells into patients, and this maintained a modest but persistent following.2,5
Traditional Use of Glandular Therapies for Pets
Traditional use of glandular therapies has persisted despite a lack of large amounts of published clinical studies. Unvalidated claims of benefits have resulted in the assumption that glandular or cellular therapies are unproven and unscientific. During the middle of the twentieth century, improvement and increase in analytical methods determined that there are many important hormones that could be isolated from glandular tissues, including cortisone from adrenal tissue and thyroxine from thyroid tissue. Scientists and clinicians then rapidly assigned all benefits of glandular tissues to the hormones that were extracted. As pharmacological research moved forward, a shift occurred toward the synthetic production of these hormones, which was more sustainable and more lucrative. The challenge was then to explain how intact glandular materials could be superior to an isolated synthetic hormone, or how they might be absorbed from the gastrointestinal tract in active forms, resisting degradation to constituent amino acids and fatty acids during digestion. Another challenge was to also prove that effects could be targeted to the organ of interest, particularly when the glandular was derived from a different species.
The Issue of Absorption of Larger Macromolecules
It has been assumed that all ingested foods are broken down into their smaller constituent molecules: proteins, fats, and carbohydrates that become amino acids, fatty acids, glycerol, and carbon skeletons and glucose. Studies since the 1970s, however, have shown that an array of larger hormones, enzymes, and peptides can be in fact absorbed totally and partially intact across the gut wall.6-8 Proteolytic enzymes bromelain and chymotrypsin with radioactive labeling have been demonstrated to be absorbed intact.9,10 Larger antigenic proteins may cross the gut barrier and induce immunologic reactions.11 Non-protein macromolecules may be absorbed intact such as dextran, heparin, and bacterial polysaccharides.6 A hypothesis of “distributed digestion” was proposed by W.A. Hemmings, which theorizes that after larger intact proteins and peptides are absorbed, digestion and metabolism will occur in peripheral tissues.7 Distributed digestion might also serve as a mechanism of communication between the gut and the rest of the body – in essence maintaining “tone” of gut-associated lymphatic tissue (GALT) and modulation of gut microbiota. Current studies of the brain-gut axis may further support this concept. More research and clinical trials are needed to understand the potential supportive effects of glandular therapies, absorption of tissue specific macromolecules, and how they can exert beneficial biological effects on specific organs.
Activity at Specific Tissues or Organs
The uptake of tissue with specific, radioactively labeled molecules has been demonstrated by target tissue with a more rapid and increased uptake in injured organs or tissues.12,13 Thyroid cells given to animals pretreated with thyrotoxins demonstrated accelerated regeneration of thyroid tissue and liver extracts infused in test animals induced liver growth.14 Studies in humans and companion animals to corroborate these findings have not been performed.
Glandular Tissues As A Source of Bioactive Ingredients
Glandular tissues are a source of peptide hormones, and today there are many well-known peptide hormones that could potentially be derived from glandular tissues: the hypothalamic peptides’ thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), and posterior pituitary hormone vasopressin.7 Partially degraded peptides may also exert activity indirectly by competitively binding to enzyme receptors, thus creating a “peptide sparing” effect.15 Competitive enzyme receptor binding by glandular derived peptides may also inhibit degradation of active endogenous hormones and extend their activity and/or enhance the total biological effect. Much research has been done on peptide hormones from animal derived whole tissues including insulin and thyroxine (pigs; cattle), as well as calcitonin and thymus.16-18
Glandular Tissues and Low-Dose Hormones
Whole glandular materials contain active substances that have been identified as hormones, hormone-like substances, hormone fragments, and other substances with biologic activity. The amounts of a single hormone within glandular materials may be too low to treat clinically significant hormone deficiency states. The use of a pharmacological dose of a single hormone used in medical treatments may potentially create a “relative deficiency” of other related hormones and bioactive factors. Here the use of glandular materials with low levels of multiple hormones and other bioactives may be a safe and natural way to support the body’s interrelated endocrine system. Furthermore, although individual hormone amounts may be lower, a glandular with multiple hormones, enzymes, and nutrients may help to support or maintain healthy body functions. For example, with functional health issues such as those seen with aging, poor nutrition, and/or low-level, chronic environmental toxin exposures, glandular therapy with its “broad array of low potency actives and nutrients” may be beneficial.
Glandular Tissues As A Source of Lipids and Steroids
A diversity of fat-soluble compounds have been found in high amounts in glandular tissues including Coenzyme Q10 (heart, liver, kidneys, spleen), phosphatidylcholine, and phosphatidylserine, which may be useful in treatment of neurologic and other diseases.19,20 Glandular tissues also contain polyunsaturated omega-3 fatty acids which have known benefits in numerous health conditions in both humans and companion animals.21 While isolated adrenal hormones became favored for treatment of adrenal insufficiency disorders (cortisone and desoxycorticosterone), it was recognized in the 1970s and 1980s that whole glandular tissues provided androgen activity, including dehydroepiandrosterone (DHEA), which had important metabolic and therapeutic effects.
Glandular Tissues As A Source of Enzymes
The most well-known and widely accepted practice for glandular therapy is the use of pancreatic enzymes from pancreatic tissue for the treatment of exocrine pancreatic insufficiency. Some may argue this is not classic glandular therapy as the pancreatic enzymes function only locally, i.e., in the gut lumen. There is some data, however, that shows intact digestive enzyme molecules may be absorbed farther down the gastrointestinal tract and actually transported back to the pancreas for storage and later release. This would facilitate a longer lasting effect of enzyme supplementation.22 This enterohepatic circulation of digestive enzymes is well demonstrated with liver produced primary and secondary bile acids. Adrenal tissue extracts also contain enzymes capable of converting the steroid precursor cholesterol into active hormones such as cortisone.23 Other glands such as ovaries or testes may contain similar enzymes that could convert precursors into their respective active hormones. Thus, glands and their extracts may contain not just small quantities of the active hormones but also the enzymes needed to endogenously synthesize the active hormones as well.
Oral Tolerance and Autoimmune Diseases
Glandular tissues may also play a role in modulating the immune system. It is known that ingested proteins can potentially act as antigens if not properly recognized by the gut-associated lymphoid tissues (GALT) to establish oral tolerance. Promoting oral tolerance helps to inhibit the body’s inappropriate immune attack of its own tissues and proteins (autoimmunity). Glandular tissues can contain small proteins or peptides that directly or indirectly promote oral tolerance and a balanced immune response.
This strategy has been employed in the treatment of both human and animal autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and uveitis.24 Oral tolerance has been used to suppress autoimmunity in animals in the treatment of uveitis, diabetes, arthritis, myasthenia gravis, and encephalomyelitis in the rat.25-29 In humans, a double-blind study on the treatment of multiple sclerosis (MS) with oral administration of bovine myelin for one year demonstrated a decrease in the number of MS attacks compared with a placebo control group.30 Perhaps the most well-known use of oral tolerance is immunotherapy delivered sublingually or orally in dogs for atopic dermatitis.31
Glandular therapy is an important medical practice for animals and humans alike. Its ancient use in Egyptian and Ayurvedic medicine is characterized by a rich history that paved the way for modern use and application to a wide variety of health contexts, with glandular tissues available as a source of bioactive ingredients, lipids, steroids, and enzymes.