Ancient Egyptian medicine and Ayurvedic writings from several hundred years B.C. mention therapeutic use of animal tissues and glandular materials.₁ A 16^th 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 19^th 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 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.

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.

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 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

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.

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.

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.