IngredientsCommon names: animal tissue supplements, glandular extracts, glandulars, organ extracts, organotherapy products, whole-food supplements, tissue extracts, protomorphogens.
Definition and scope: The term glandular extract has come to be an umbrella term used to describe both animal glandular and organ extracts that are ingested to nourish and support the corresponding human gland or organ. More broadly, whole-food supplements, or glandular therapies, are supplements made from the glands, organs, or tissues of healthy animals. Also known as organotherapy, tissue therapy, or cell therapy, glandular therapies are characterized by the use of animal tissues to produce biological effects in humans or other animals.
Animal sources: The glandular extracts used today are products made from the dried and powdered glandular (or organ) tissue of animals such as sheep (ovine), pigs (porcine), and cows (bovine). Among the most frequently encountered sources are:
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). Specific tissues and organs used in supplements include liver powder, orchic (testicular) extracts, ovaries, eye tissue, mammary tissue, glandular powders or extracts such as adrenal gland and thyroid gland, or specific substances extracted from glands or tissues such as melatonin extracted from the pineal gland.
Common dosage forms and preparations: These supplements may be administered as whole fresh tissue or as tissue extracts. Several distinct manufacturing methods exist:
Animal glands have been valued as food and as medicine for millennia. Glandular therapy and whole tissue supplementation have their roots in ancient cultures, as shown by the belief that the health or function of a specific body part could be enhanced by consuming the same organ from a specific animal. Throughout history, people have used glandular tissues as food and as nutritional supplementation. Many different cultures often ate organs and glands from animals or fish to improve their general health or to treat specific ailments.
The notion that eating a specific organ can strengthen the same organ in the body has deep historical roots. Ancient cultures, from Traditional Chinese Medicine to Native American healing practices, consumed organs to promote vitality and well-being. For the Eskimos of Alaska, the native diet consisted of a liberal use of organs and other special tissues of the large animal life of the sea, as well as of fish.
The formal medical-scientific use of animal tissue extracts began in the late nineteenth century. With the development of endocrinology (the study of hormones, glandular organs, and their function), and the understanding of the actions of hormones on the body, glandular therapy acquired a basis in science and gained popularity as a form of medical treatment.
The earliest oral treatment for hypothyroidism consisted of thyroid extract. George Redmayne Murray of the United Kingdom first described treatment of myxedema with thyroid extract in 1891, and published a description of long-term successful treatment (28 years) of a patient with myxedema (severe hypothyroidism) in 1920. His treatment was quickly adopted in North America and Europe. In the late 1800s, treatment with thyroid extract caused dramatic improvement in patients with myxedema. Shortly thereafter, multiple other glandular extracts became available, both individually and in combinations. Their use gradually fell into disfavor, partly due to overpromotion by the manufacturers.
Thyroid glandular extracts were considered standard treatment for hypothyroidism, and doctors successfully prescribed bovine thyroid gland extract to hundreds of thousands of patients in the USA alone. In 1965, approximately 4 of every 5 prescriptions for thyroid hormone in the USA were for natural thyroid preparations.
The use of animal liver extract to treat pernicious anemia represents one of the most clinically significant episodes in the history of glandular therapy. The initial discovery resulted from the need to find a cause and treatment of pernicious anemia, first described by Thomas Addison in 1849. A cure was discovered in 1926 when consumption of lightly cooked liver resulted in correction of anemia and prevention of death, although at the time it was believed that proteins and iron in the liver were the curative factors. Edwin Cohn prepared a liver extract that was 50 to 100 times more potent in treating pernicious anemia than the natural liver products. William Castle demonstrated that gastric juice contained an "intrinsic factor" which when combined with meat ingestion resulted in absorption of the vitamin. In 1934, George Whipple shared the Nobel Prize in Physiology or Medicine with William P. Murphy and George Minot for discovery of an effective treatment for pernicious anemia using liver concentrate, later found to contain a large amount of vitamin B12.
In 1905, the embryologist John Beard first proposed that pancreatic proteolytic enzymes had potential as a treatment for cancer. His theories were dismissed by the medical world a decade later, but various practitioners have kept the concept alive through the publication of case reports of cancer patients treated with pancreatic proteolytic enzymes. Separately, dried pancreas extracts were used as a digestive aid for conditions including diabetes in the pre-insulin era. Early in the twentieth century, physicians used glandular extracts as an actual source of hormones. For example, extracts of ovaries were used to supply female hormones such as progesterone.
Other enlightened doctors worked out that one of the best treatments for those with Addison's disease (adrenal insufficiency) was to give the patient a bovine adrenal gland extract. Research in the 1950s discovered that adrenal extracts contain enzymes that assist in the conversion of cholesterol to various glucocorticoids as well as their precursors.
Researchers found that calf thymus extracts restore immune function in thymectomized neonatal animals. Manufacturers then began making extracts of thymus tissue to treat disorders of the immune system. Several studies in the 1980s used the thymus extract thymomodulin, an acid-processed and partially-purified product.
As chemists and biochemists developed improved analytical and extraction methods, the medical profession embraced the use of pharmacologic doses of pure hormones and other pharmaceutical agents for therapy, either as natural or synthetic products, rather than "glandulars." Physiologists, nutritionists, and medical professionals accepted the idea that other tissue constituents such as proteins, fats, and carbohydrates were not absorbed intact, but were broken down into their amino acid, fatty acid, or simple sugar components. Consequently, the scientific community generally abandoned glandular therapy in favor of pure drug treatments.
From 1940 to the 1980s, little was done to advance the therapeutic use or clinical research of glandular tissues. With the exception of whole thyroid extracts (Armour Thyroid and others), most other glandular therapy products disappeared.
A few of the glandulars listed above are still in general use today, although most have fallen out of favour in the supplement community, particularly those extracted from organ tissue. Increased restrictions on sales internationally, combined with fears of contamination with toxins or diseases have led to interest more towards other therapeutic ideas such as diet and lifestyle changes, supportive herbs and direct supplementation of nutrients to treat glandular and organ deterioration.
Whole glandular products and tissues are good sources of enzymes, fats, steroids, proteins, and nutraceuticals. The precise composition differs substantially by tissue type, but general constituent classes include:
Two major theoretical frameworks underpin the claimed mechanisms of glandular therapy:
The "Like Heals Like" (Homologous Organ Support) Principle: 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. Dr. Lee and other early nutritional pioneers felt the degenerative processes of a specific organ could be reversed by ingesting the necessary raw materials peculiar to that organ.
Direct Supply of Biologically Active Molecules: The second concept is that ingestion of glandular tissues will provide the body with hormones or other biologically active substances that are normally secreted by that gland. Low doses of supplemental enzymes and hormones, such as the levels that would be found in these tissues or their extracts, may have a sparing effect on a patient with a functional problem such as hormone deficiency, by supplying an external source of the hormone without suppressing the body's natural production. This is in contrast to the use of high or pharmacologic doses of purified hormones, which are believed to inhibit further hormone production by the body itself.
Macromolecular Absorption: A principal scientific objection to glandular therapy has been the presumption that large biological molecules are fully digested before absorption. However, this view has been substantially refined. The principal challenges to oral glandular therapy were the lack of evidence that large molecules were absorbed intact across the intestinal wall and the lack of evidence that ingested materials could exert specific effects on target tissues. However, in the past few decades, researchers have demonstrated, through radioactive and dye studies, that large hormones, enzymes, proteins and peptides are routinely absorbed intact or only partially degraded and that these constituents can concentrate in target tissues.
Numerous whole proteins have been shown in human and animal studies to be absorbed intact into the bloodstream after oral administration. 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.
Laboratory studies have documented a more rapid uptake of tagged cells or their components by traumatized organs than normal organs, and some studies show enhanced healing rates of damaged tissues.
Oral Tolerance / Oral Tolerization: Scientific interest in the therapeutic potential for gland and organ tissues has increased with advances in oral tolerance or oral tolerization (OT). In terms of gland or organ therapy, OT refers to the process of feeding specific animal proteins, termed oral auto-antigens, to a patient with an autoimmune condition.
Active Peptides: Active peptides are defined as specific regions of proteins with a part of 20 natural amino acid sequences in a certain order and structure and have certain biological or physiological effects. Diverse types and orders of amino acids determine their extensive functions. Previous studies have demonstrated that active peptides possess multiple biological activities, including growth promotion, immune regulation, antioxidant, antihypertensive, antithrombotic, antiadipogenic, antimicrobial, and anti-inflammatory and immunomodulatory effects.
Desiccated thyroid extract, derived from porcine or bovine thyroid glands, is the most extensively studied and longest-used animal tissue preparation in modern medicine. Desiccated thyroid extract is a thyroid hormone pill made from animal thyroid glands. Currently desiccated thyroid extract is made from pig thyroids and is available as Armour Thyroid™ and Nature-Throid™.
Prior to the advent of synthetic T4 and synthetic T3, patients with hypothyroid disease were treated with desiccated thyroid. Desiccated thyroid is known to contain both thyroid hormones, T3 and T4, and successfully normalize TSH in hypothyroid patients. Although desiccated and purified thyroid has had a long history of therapeutic use, there are a limited number of clinical trials which demonstrate its effectiveness in comparison to the standard of care, synthetic T4.
Key randomized controlled trial (Hoang et al., 2013): To date, there has been one double-blinded, randomized study which compared desiccated thyroid (Armour Thyroid) to synthetic T4. This single-center study was run by Walter Reed National Military Medical Center. A total of 70 previously hypothyroid patients, then euthyroid on replacement therapy, were enrolled in this cross-over study and were randomized to either synthetic T4 or Armour Thyroid. The primary endpoint of this study showed no difference between synthetic T4 and Armour Thyroid for symptom scores, health questionnaires, or neuropsychological tests. All patients remained within acceptable TSH range at the end of each study period, demonstrating that hypothyroid patients can be safely and effectively switched between synthetic T4 and Armour Thyroid.
Prospective crossover study (75 patients): A prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to one of three treatment arms—LT4, LT4 + LT3, and DTE—for 22 weeks was conducted. The primary outcomes were post-treatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), the 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale, and the Beck Depression Inventory.
It was not until 1985 that revision of the U.S. Pharmacopeia standard from iodine content to L-liothyronine (T3)/L-thyroxine (T4) content resulted in stable potency after earlier concerns; but by then the move to levothyroxine was nearly complete in many countries, so that levothyroxine largely replaced NDT. With its more favorable pharmacokinetics allowing for once daily dosing and clinical trial evidence, levothyroxine monotherapy has prevailed as the treatment of choice for primary hypothyroidism.
Evidence strength: For prescription-grade NDT, evidence is moderate, consisting of a small number of randomized controlled trials. The overall body of evidence does not demonstrate consistent superiority of DTE over levothyroxine, but DTE is an accepted alternative in certain clinical contexts, particularly for patients who remain symptomatic on standard levothyroxine therapy.
Dosage: For initiation of NDT, the therapy is usually instituted using low doses, with increments which depend on the cardiovascular status of the patient. The usual starting dose is 30 mg of Armour Thyroid with increments of 15 mg every 2 to 3 weeks.
Pancreatin is a mixture of several digestive enzymes produced by the exocrine cells of the pancreas. It is composed of amylase, lipase, and protease. This mixture is used to treat conditions in which pancreatic secretions are deficient, such as surgical pancreatectomy, pancreatitis, and cystic fibrosis.
Pancreaze (pancrelipase) Delayed-Release Capsules is a combination of porcine-derived lipases, proteases, and amylases indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis, or other conditions. Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery.
Although meta-analyses have confirmed that enzyme therapy is superior to placebo, there is no evidence that one product is superior to another or that any will reliably eliminate steatorrhea.
The use of pancreatic enzyme supplementation from pancreatic tissue extracts is a common form of veterinary therapy for a condition in dogs known as Exocrine Pancreatic Deficiency. It was thought that the effect of the enzymes found in pancreatic tissue extract was limited to the lumen or inside of the intestinal tract, where local enzymatic digestion occurred. However, now there is evidence that the enzymes are reabsorbed and recirculated in the body (a process called enteropancreatic circulation). Once absorbed into the circulation, these enzymes may contribute to other reactions in other organs.
Evidence strength: PERT is among the best-supported applications of animal tissue supplementation, backed by randomized controlled trials and meta-analyses, and represents standard-of-care medical practice in this context.
Dosage: Pancreaze is available in dosages of 2,600; 4,200; 10,500; 16,800; and 21,000 lipase units per capsule.
The clinical application of liver extract to pernicious anemia is one of the foundational discoveries in nutritional medicine. Early research pursued a treatment for pernicious anaemia and led to the subsequent discovery of vitamin B12 and the intrinsic factor. Castle's experiments established the theory of extrinsic and intrinsic factors as hemopoietic principles, and studies on purification of the anti-pernicious anaemia principle from liver tissue terminated in the crystallization of vitamin B12 and identification of its coenzyme forms.
Patients with pernicious anemia were maintained in clinical remission with oral therapy (liver extracts or intrinsic factor concentrate with vitamin B12) for as long as 29 years.
In the late 1940s, two groups announced the discovery of a new vitamin, purified and crystallized from liver, that induced and maintained remission of pernicious anemia.
Evidence strength: This is the highest-quality evidence in the entire field of animal tissue supplementation — the Nobel Prize-winning discovery definitively established liver tissue as a source of a critical anti-pernicious anemia factor, later identified as vitamin B12. Isolated B12 is now the preferred treatment rather than crude liver extract, but the discovery illustrates the valid pharmacological content of organ tissue.
Chicken type II collagen (CCII), extracted from chicken sternal cartilage, has been studied as a dietary intervention to induce immune tolerance in rheumatoid arthritis (RA). Chicken type II collagen (CCII) is a protein extracted from the cartilage of chicken breast and exhibits intriguing possibilities for the treatment of autoimmune diseases by inducing oral tolerance.
Mechanism of action: Oral administration of CII is an established procedure for inducing peripheral immune tolerance, which suppresses autoimmune responses in RA. Animal studies have revealed that the mechanisms of induction of oral tolerance include clonal deletion, suppression of the pro-inflammatory Th1 cells, and the induction of regulatory T (Treg) cells.
Initial clinical trial (Trentham et al., 1993, published in Science): In a randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident.
Larger multicenter phase III study (Wei et al., 2009): A 24-week, double-blind, double-dummy, randomized, methotrexate (MTX)-controlled study was conducted to evaluate the efficacy and safety of CCII in the treatment of rheumatoid arthritis (RA). Five hundred three RA patients were included in the study. Patients received either 0.1 mg daily of CCII (n = 326) or 10 mg once a week of MTX (n = 177) for 24 weeks. With an intention-to-treat analysis, response rates for ACR-20 were 30.51% in the CCII group and 44.94% in the methotrexate (MTX) group at 12 weeks.
In both groups there was a decrease in pain, morning stiffness, tender joint count, swollen joint count, Health Assessment Questionnaire score, and investigator and patient assessment of function; all differences were statistically significant.
Whether oral administration of Type II collagen is an efficacious treatment for humans with established active RA has not been established.
Evidence strength: Preliminary to moderate. The initial small trial was promising. Larger trials showed some benefit, but CCII was inferior to methotrexate on standard outcome measures. The mechanism via oral tolerance is biologically plausible and supported by animal data, but human evidence remains insufficient to establish CCII as a standard treatment.
Researchers found that calf thymus extracts restore immune function in thymectomized neonatal animals. Manufacturers then began making extracts of thymus tissue to treat disorders of the immune system. Several studies in the 1980s used the thymus extract thymomodulin, an acid-processed and partially-purified product. A 1989 review article reported that it was helpful for infections and allergies and that it improved immunologic functions in older adults. In a retrospective study of 130 patients with different illnesses who received thymomodulin, those with an initial CD4+/CD8+ ratio outside the normal range (whether high or low) had a normalization of the ratio.
Evidence strength: Preliminary. The evidence base for thymus extract in immune modulation is largely composed of early, often small clinical studies and animal experiments conducted predominantly in the 1980s. Rigorous modern randomized controlled trials are lacking.
Adrenal extracts are made from the adrenal glands of cows, pigs, or other animals. According to a theory prevalent in alternative medicine, the consumption of adrenal extracts can strengthen the function of an underperforming or exhausted adrenal gland. However, there is no scientific evidence to support this belief and no rational justification to indicate that it might be true.
Animal adrenal glands may contain significant levels of adrenal hormones. This is the basis for some recommended uses of adrenal extracts, such as allergies, asthma, and rheumatoid arthritis (conditions that respond to cortisone). However, modern adrenal extracts are manufactured so they do not contain significant levels of adrenal hormones.
Evidence strength: Very weak. There are no high-quality clinical trials supporting the use of adrenal extracts for "adrenal fatigue" or any other condition recognized by mainstream endocrinology. The concept of "adrenal fatigue" itself is not recognized as a medical diagnosis.
Orchic extract (also labeled bovine orchic/testicular extract) is a glandular supplement made from cattle testes. It is marketed for "testicular support," libido, and testosterone — but there is no good clinical evidence in humans that it improves testosterone, sexual function, fertility, prostate health, or urinary symptoms. Major consumer-health monographs conclude that efficacy is unproven and safety is uncertain due to the animal origin of the raw material.
Evidence strength: No quality clinical evidence exists in humans. This category of glandular supplement has no substantiated benefit in the peer-reviewed literature.
Dosage information for animal tissue supplements varies substantially by tissue type, manufacturer, and preparation method. The following dosages are those specifically documented in the research literature:
It should also be noted that a critical distinction exists between prescription-grade desiccated thyroid medications (NDT), which are standardized and regulated, and over-the-counter glandular supplements, which are not. NDT medications like Armour, Nature-Throid, and NP Thyroid are prescription-only and strictly regulated by the FDA. Each dose contains a carefully measured ratio of T3 and T4, so doctors can prescribe and adjust it based on blood test results.
Glandular products are marketed as nutritional supplements and are not stringently regulated by the FDA. Products may differ in formulations and strengths, and labels may not always match contents. This stands in sharp contrast to prescription NDT preparations, which are fully regulated pharmaceuticals.
Some glandular preparations retain actual thyroid hormones such as T3 (triiodothyronine) and T4 (thyroxine). If a glandular supplement contains active T3 and T4, a person could unknowingly push the body into hyperthyroidism. This can lead to anxiety, heart palpitations, high blood pressure, muscle weakness, insomnia, and—in severe cases—heart failure or bone loss. Independent testing has shown that many thyroid supplements contain inconsistent hormone levels, sometimes at prescription strength.
Overdose of glandular products can have serious adverse effects because each product can overstimulate the particular organ's function. For instance, overdose of thyroid extract can lead to overactive thyroid (hyperthyroidism) and overdose of liver extract can cause iron overload. Treatment of glandular products overdose includes discontinuation of the product and appropriate symptomatic and supportive care.
The FDA has issued a final rule prohibiting the use of certain cattle material to address the potential risk of bovine spongiform encephalopathy (BSE) in human food, including dietary supplements, and cosmetics. The following items are designated as prohibited cattle materials: Specified risk materials (SRMs), the small intestine from all cattle (unless the distal ileum has been removed), material from nonambulatory disabled cattle, material from cattle not inspected and passed, or mechanically separated beef. This action is taken to minimize human exposure to certain cattle material that could potentially contain the BSE agent.
The U.S. FDA's 2016 final rule prohibits certain high-risk cattle materials (specified risk materials such as brain, spinal cord, dorsal root ganglia from older cattle; tonsils and distal ileum from all cattle) in human foods, including dietary supplements, to mitigate BSE risk. This regulation reduces—but does not absolutely eliminate—theoretical risks from bovine-derived ingredients; it does not certify that any particular glandular is safe or effective.
Supplements made from the brains, eyes, and glands of cattle may expose consumers to more risk from Mad Cow Disease than do meat products. This is because the consumer is directly exposed to the tissues that contain the highest concentrations of the mutant proteins that cause Mad Cow Disease. As little as 100 milligrams of infected tissue would be enough to cause vCJD, but the recommended daily dose of most glandular supplements is at least 300 milligrams.
A number of dietary supplement products use bovine-derived tissues or extracts of such tissues as ingredients. These ingredients include specific tissues and organs or their extracts (e.g., liver powder, orchic extracts, ovaries, eye tissue, mammary tissue), glandular powders or extracts (e.g., adrenal gland, thyroid gland), or specific substances extracted from glands or tissues (e.g., melatonin extracted from the pineal gland).
Because glandulars are derived from animal tissues, there is always a potential risk of contamination with bacteria, viruses, or even prions. While this risk is low, it is not zero, especially with poorly regulated supplements. Since the fat is not removed in certain preparations, potentially harmful contaminants that accumulate in fat tissue may remain in the product. It is therefore critical that the glands be derived from livestock that have grazed on open ranges that are not sprayed with pesticides or herbicides. The animals should also be free of antibiotics, synthetic hormones, and infection.
There are few, if any, side effects of this form of supplementation. Theoretically, patients sensitive to meat from certain species may exhibit allergic reactions to corresponding glandular preparations. Individuals with known meat allergies should exercise caution.
Animal tissue supplements containing active hormones can interact with pharmaceutical hormone therapies. Thyroid glandular products containing T3 and T4 could significantly alter response to thyroid medications, anticoagulants (thyroid hormone potentiates warfarin), and antidiabetic agents. Liver extracts containing high levels of vitamin K can interact with anticoagulant drugs. Adrenal extracts with residual corticosteroid activity may theoretically alter immune and metabolic function. These interactions are conceptual or case-based in origin, as robust drug-interaction studies on raw glandular products are generally absent from the peer-reviewed literature.
Despite some scientific support for individual glandular preparations, 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.
Classic double-blinded cross-over studies on glandular therapy have not been performed, and data supporting the use of glandulars is primarily based on historical use. The quality and quantity of evidence varies substantially by preparation type:
The history of the use of thyroid, pancreatic, adrenal, thymus, and liver extracts suggests that glandular extracts can be beneficial, especially when potential mechanisms of action and methods of preparation are considered. However, this statement from a historical review must be set against the broader consensus: some manufacturers of glandular products claim that the animal version of an organ provides nutrients that support the corresponding organ in humans. However, there is no evidence that the human adrenal gland requires any nutrients uniquely available in animal adrenals. This observation, made specifically for adrenal extracts by EBSCO Research Starters, applies with varying force to the majority of unvalidated glandular categories.
Health conditions that Animal tissue may help support.
Body systems that Animal tissue may help support.
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