Whole Adrenal Glandular
1. Identity: Names, Source, and Forms
Common and Technical Names
Whole adrenal glandular is known by a variety of synonyms in commerce and the scientific literature, including adrenal cortical extract (ACE), adrenal extract, adrenal gland extract, adrenal concentrate, adrenal cortex extract, adrenal factors, adrenal medulla, adrenal polypeptide fractions, adrenal powder, adrenal substance, lyophilized adrenal tissue, and whole adrenal extract. The French equivalents Extrait de Glandes Surrénales Entières and Tissu Lyophilisé de Glande Surrénale appear in some international regulatory and commercial contexts.
Biological Source
Adrenal extract is a chemical made from the adrenal glands of slaughtered cows, pigs, and sheep. Commercially available adrenal extracts are made using the whole gland (whole or total adrenal extracts) or just the cortex, or outer portion of the gland (adrenal cortex extracts). The bovine source predominates in most commercially sold supplements sold in North America and Europe.
The adrenal glands are small, triangular organs located atop each kidney. The adrenal glands are uniquely structured to support stress adaptation. Their two functional regions—the cortex and the medulla—coordinate distinct but complementary physiological processes, allowing the body to respond to both immediate and longer-term demands.
Anatomical Distinction: Whole Gland vs. Cortex Only
Oral adrenal extracts have been used in medicine since at least 1931. 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).
Preparation and Dosage Forms
Glandular tissue must be collected and processed in a way that creates a stable product suitable for tablets or capsules. Commonly used methods include azeotropic processing, salt precipitation, and lyophilization.
- Azeotropic processing: The glandular material is frozen, then washed with a solvent to remove the fat. The solvent is distilled off and the remaining material is dried and ground into a powder. By removing the fat, fat-soluble products are also removed—beneficial in the case of toxins and detrimental in the case of essential fatty acids and fat-soluble hormones. Additionally, traces of the solvent may remain.
- Salt precipitation: The glandular material is ground in salt and water, then centrifuged to separate the heavier proteins from the lighter fat.
- Lyophilization (freeze-drying): Also known as freeze-drying, this method involves freezing the material, then removing the water at low pressure and low temperature. Unlike the other two methods, the fat remains in the finished product, together with fat-soluble materials and many other components that might be degraded or removed by the harsher processing of the azeotropic or salt-precipitation methods. For materials obtained through this method, it is important that they be from animals raised in an environment that is as clean as possible.
The finished product is typically sold as capsules or tablets. Manufacturers dry and process the gland tissue into capsules, with commercial doses ranging from about 50 mg to 350 mg per capsule. It can be taken by mouth, placed under the tongue (sublingually), or, historically, injected intravenously.
Product sourcing is a key variable; some preparations are sourced from range-grazed, government-inspected animals in New Zealand and Australia, preserving vital nutrients and bioactive compounds.
2. Traditional and Historical Use
Ancient and Pre-Modern Antecedents
Animal glands have been valued as food and as medicine for millennia. The use of glandular therapy dates back thousands of years in traditional Chinese medicine (TCM), and began in Western medicine in the 19th century, gaining traction in the early twentieth century. The philosophical basis of glandular therapy is that oral ingestion of an animal gland—such as the liver, spleen, thyroid, etc.—will strengthen the function of the corresponding gland in humans. Using the glands or other organs of animals for medicinal treatment, also called organotherapy, goes back to ancient medical times, part of the timeless phenomenon known as "like heals like."
19th-Century Organotherapy
Despite criticism of early organotherapy, by the end of the 19th century the practice of clinical medicine had vastly changed. Organotherapy, deemed questionable when applied to the testis, became accepted treatment for other glandular-deficient states. Practitioners "rediscovered" that certain organs had internal secretions. By 1910, physicians and scientists spoke of "hormones" to describe the chemical messengers previously known as internal secretions. Elucidation of hormones from the adrenal and thyroid glands was heralded as a vital addition to the physician's repertoire.
After scientists discovered the clinical usefulness of dried thyroid gland in the 1890s, a wide variety of glandular products came into use. Decades earlier, Addison had described patients with hypotension, nausea and abdominal pain, skin pigmentation, and eventual death, with abnormal adrenals.
Early 20th-Century Medical Use
Historically, adrenal extracts were introduced in the early 20th century, believed to support vitality, combat fatigue, and address symptoms associated with adrenal insufficiency. Before the development of synthetic hormones like cortisone, adrenal extracts were sometimes used therapeutically. Before the advent of modern corticosteroid medications, adrenal extracts were often prescribed to support individuals suffering from Addison's disease, fatigue, low blood pressure, and general exhaustion.
Beginning in the 1920s, adrenal cortical extract (ACE) was recommended for treating Addison's disease (adrenocortical insufficiency), a condition in which gradual destruction of the cortex of the adrenal glands leads to a potentially fatal hormonal deficiency. However, as more effective synthetic and purified products became available, use of the crude extract became pointless.
A notable early case involved pharmacology professor Muirhead, who had Addison's disease. Clinicians used adrenal glandular material, raw or dried and formed into a tablet, to treat conditions such as asthma with some success. In 1920, Muirhead devised a treatment that required 1200 mg of dried adrenal, described as "1 part representing 5 parts fresh capsule," recommended for the treatment of Addison's disease, hay fever, and neurasthenia.
Henry R. Harrower, MD (1883–1934), was a leading practitioner of organotherapy, eventually creating The Harrower Laboratory in Glendale, California, which produced, marketed, and distributed organotherapy products on an industrial scale. He authored a series of publications entitled "Harrower's Monographs on the Internal Secretions" and compiled them into the books "Practical Hormone Therapy" and "Practical Organotherapy—The Internal Secretions in General Practice."
Multiple glandular extracts became available both individually and in combinations. Their use gradually fell into disfavor, partly due to overpromotion by the manufacturers. In the 1930s, glandular therapy was common practice, but during the 1940s and 50s with the advent of antibiotics and the isolation of vitamins and hormones, glandular therapy lost its way. Whole glandular concentrates supply multiple factors, but do not include hormones.
Regulatory Withdrawal in Conventional Medicine
Oral adrenal glandular materials fell out of use by the medical establishment when manufacturers devised methods of large-scale corticosteroid production in the 1940s. In January 1978, the Food and Drug Administration (FDA) advised drug firms marketing ACE products that the drug represented a substantial risk of undertreatment because of its low potency and the resulting potential hazard to patients. The 1971 edition of the American Medical Association's Drug Evaluations called ACE an "obsolete preparation."
Persistence in Naturopathic and Integrative Medicine
Although glandular therapy has since fallen into disuse within conventional medicine, it is still used within TCM and modern naturopathic medicine. The use of whole adrenal glandulars became more common in the mid-20th century, particularly during the rise of alternative medicine and nutritional supplementation. "Adrenal fatigue"—a controversial condition not recognized by mainstream medicine—became a term to describe chronic exhaustion and low energy resulting from stress and poor adrenal function. Adrenal glandular supplements were marketed as a natural solution to support the adrenal glands and improve symptoms of fatigue, low energy, and burnout, though the clinical evidence supporting these claims remains limited.
3. Key Constituents and Proposed Mechanisms of Action
Biochemical Composition
Adrenal extract contains a complex mix of peptides, proteins, enzymes, and—depending on the purification process—very small amounts of natural adrenal hormones (cortisol, aldosterone, DHEA, etc.). Most reputable supplements specify that they are "hormone-free," meaning the extraction process removes active hormones, but the degree of removal is rarely absolute. Some products, however, are intentionally left with trace hormones for a "glandular therapy" effect.
The scientific basis for the use of animal glandulars is that they contain hormones, hormone precursors, and an array of nutrients such as vitamins and minerals. Preparations from healthy organs can supply substances that may be deficient in the corresponding organ in vivo, including nucleic acids and organ-specific enzymes. They may also include glycosaminoglycans, glycolipids and phospholipids, enzyme cofactors, mineral storage proteins and other substances.
From the whole gland, the two tissue regions contribute distinct compound classes:
- Adrenal cortex tissue provides nutrients associated with the synthesis of steroid hormones such as cortisol, aldosterone, and DHEA.
- Adrenal medulla tissue contributes factors related to the synthesis of catecholamines epinephrine and norepinephrine.
The adrenal glands in cows play a similar role and make similar hormones to those in humans. As a result, their adrenal glands contain small amounts of cortisol, aldosterone, adrenaline, and other hormones. The actual amount of each hormone in an adrenal extract is expected to be very small, and the content may vary depending on the individual animal and the way the product was processed. It is also not clear how well the body absorbs these hormones when they are taken orally.
Cortisol Concentration in Bovine Tissue
The concentration of cortisol in bovine adrenal gland is quite low, between 2 and 4 micrograms per gram. A 200 mg capsule would require roughly one gram of raw material to produce, containing only 4–5 micrograms of cortisol. While some clinicians worry about adrenal suppression when they hear a patient has been taking adrenal glandular, the supplement cannot contain enough corticosteroid to cause it.
Proposed Mechanisms
The use of animal-derived glandular tissues such as bovine adrenal cortex is rooted in a historical medical practice known as organotherapy. Dating back to the late 19th and early 20th centuries, organotherapy operates on the principle of "like supports like"—the theory that consuming the specific tissue of a healthy animal can provide targeted nutritional support, repair, and normalization to the corresponding organ in a human. While modern pharmacology has largely shifted toward isolating and synthesizing single active compounds, functional and integrative medicine practitioners continue to utilize glandular extracts for their complex, synergistic profiles of nutrients, enzymes, and tissue-specific peptides.
A biologically plausible but not yet validated mechanism involves extracellular vesicles. Complementary research on dietary exosomes, particularly from bovine milk, demonstrates that extracellular vesicles can protect biologically active cargo—such as proteins, lipids, and nucleic acids—through digestion and facilitate cellular interactions. Some researchers have proposed this as a potential framework for how bioactive molecules in glandular preparations might survive digestion, but this mechanism has not been directly demonstrated for adrenal glandular supplements.
A key criticism of the "like supports like" mechanism is that some experts question the theory, noting that peptides and proteins from ingested glandulars are likely digested in the gastrointestinal tract before reaching target organs. People use adrenal extract taken from animals in the hope that the extract will function like the body's adrenal gland, but it is not known whether the human body can absorb adrenal extract or how it might work.
An intriguing open question was raised in a peer-reviewed analysis published in Integrative Medicine (2023): prior to the development of synthetic corticosteroids, Addison's disease was treated with oral desiccated whole adrenal glands or crude extracts. These products could not have contained meaningful amounts of cortisol, yet some patients improved. There may be something in whole glands that can stimulate failing adrenals to make cortisol. The identity of such a putative factor, if it exists, remains unknown.
4. Scientific Evidence by Area of Use
Overview of Evidence Base
The majority of scientific studies on glandular therapy are historical, dating to the early-to-mid 20th century, before the advent of purified hormone medications. Modern clinical trials on adrenal glandulars in humans are extremely limited, and the few available studies are often small, uncontrolled, or focused on related glandular supplements (like thyroid or pituitary glandulars). There is no large-scale, double-blind, placebo-controlled clinical trial directly validating adrenal glandular efficacy in treating "adrenal fatigue" or boosting human adrenal function. Most supporting evidence is anecdotal or comes from practitioner case reports.
4a. Addison's Disease and Adrenal Insufficiency (Historical Use)
The most historically substantiated use of adrenal glandulars is in the treatment of adrenal insufficiency (Addison's disease) in the pre-synthetic-steroid era. 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. Published case series and clinical reports from the 1920s and 1930s documented symptomatic improvements in Addison's disease patients treated with desiccated whole adrenal tissue or crude cortical extracts, as referenced in Proceedings of the Royal Society of Medicine (Hicks & Mitchell, 1935) and the Journal of the American Medical Association (Rowntree et al., 1931).
Evidence strength: These historical reports are pre-controlled-trial in design and suffer from lack of standardization, blinding, and objective outcome measurement. Modern formulations do not contain significant levels of adrenal hormones, making direct extrapolation from these historical uses to contemporary supplements scientifically unjustified.
4b. Fatigue, Stress, and "Adrenal Fatigue"
Adrenal extracts are most often used to reduce fatigue, moderate stress, and enhance resistance. However, the concept underpinning most contemporary supplementation—"adrenal fatigue"—is not supported by the scientific evidence. The term "adrenal fatigue" has been used by some doctors, healthcare providers, and the general media to describe an alleged condition caused by chronic exposure to stressful situations. However, it has not been recognized by any Endocrinology society, who claim there is no hard evidence for its existence.
An August 2016 systematic review combined and analyzed data from 58 studies on adrenal fatigue including more than 10,000 participants. The conclusion in a nutshell: "Adrenal fatigue does not exist," according to review authors in the journal BMC Endocrine Disorders. Investigators found an almost systematic finding of conflicting results derived from most of the study methods utilized. Limitations included heterogeneity of study design, the descriptive nature of most studies, poor quality assessment of fatigue, use of unsubstantiated cortisol assessment methodology, false premises leading to an incorrect sequence of research direction, and inappropriate conclusions regarding causality. The systematic review concluded that there is no substantiation that "adrenal fatigue" is an actual medical condition and that it remains a myth.
The Endocrine Society and the Hormone Health Network do not recognize adrenal fatigue as a legitimate medical condition, although many websites provide information on this topic along with unfounded recommendations for self-diagnosis and options to purchase adrenal supplements. In a March 2020 position statement, the American Association of Clinical Endocrinologists and American College of Endocrinology addressed the use of adrenal supplements "to treat common nonspecific symptoms due to 'adrenal fatigue,' an entity that has not been recognized as a legitimate diagnosis." The statement warned of known and unknown health risks of off-label use and misuse of hormones and supplements in patients without an established endocrine diagnosis.
There are no published clinical trials demonstrating efficacy for any outcome in the burnout or HPA dysregulation population.
Evidence strength: No human clinical trial evidence supports efficacy for fatigue, stress, or the "adrenal fatigue" construct. The primary clinical framework (adrenal fatigue) is not a recognized diagnosis. Evidence is absent or negative at the systematic review level.
4c. Allergic and Inflammatory Conditions
Animal adrenal glands may contain significant levels of adrenal hormones. This is the basis for some historical 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. Therefore, it is difficult to find any justification for their use along these lines.
Evidence strength: Rationale is derived from the known pharmacology of corticosteroids (which the modern supplement is unlikely to contain in meaningful amounts). No contemporary controlled clinical trial evidence supports whole adrenal glandular for allergic or inflammatory conditions.
4d. Energy, Immune Function, and General Vitality
Dietary supplements containing adrenal extract may be used to increase energy levels and boost immune and adrenal function, but their benefits for any use are not well defined. Some manufacturers suggest that consuming adrenal extracts could provide nutrients that support human adrenal function or offer immune-related benefits; however, there is no empirical evidence to validate these claims.
Evidence strength: No controlled human clinical trial evidence. Claims rest on theoretical nutritional frameworks or practitioner case reports.
4e. Hypoglycemia and Neurological/Psychiatric Symptoms
In 1949, John W. Tintera, MD (1911–1969), of Yonkers, New York, began claiming that the symptoms of "hypoadrenal syndrome" were often similar to those of hypoglycemia and included excessive fatigue, nervousness, irritability, depression, excessive weakness, lightheadedness, faintness, insomnia, headache, and inability to concentrate. He expanded this list and proclaimed that hypoglycemia was caused by "tired" or "worn out" adrenal glands. These claims enabled him and a small group of other physicians to diagnose and prescribe ACE for "hypoglycemia" in patients who had neither Addison's disease nor actual hypoglycemia.
Evidence strength: These claims were generated by a single practitioner without systematic controlled study and were not replicated or validated by subsequent research.
5. Body Systems and Health Areas Associated with Whole Adrenal Glandular
The following body systems and areas are those with which whole adrenal glandular has been historically or contemporarily associated in traditional/naturopathic use, or in research contexts. Association does not imply clinically proven efficacy.
- Endocrine system / HPA axis: The adrenal glands play a crucial role in hormone production, releasing cortisol (which regulates metabolism, immune response, and stress adaptation), and adrenaline and noradrenaline (responsible for the fight-or-flight response). Whole adrenal glandular is primarily marketed in the context of HPA axis support.
- Stress response: The adrenal glands sit on top of the kidneys and regulate the body's response to stress by making hormones, including adrenaline and cortisol.
- Immune regulation: Preparations often contain tissue from both the adrenal cortex and medulla with the intent to support healthy adrenal function, stress hormone balance, and immune regulation.
- Energy metabolism: Corticosteroids produced by the adrenal cortex influence glucose metabolism and energy availability; these functions are referenced in the traditional rationale for glandular use.
- Cardiovascular/blood pressure: Adrenal hormones including aldosterone and adrenaline directly regulate blood pressure, and adrenal extracts were historically prescribed to support individuals suffering from low blood pressure.
- Inflammatory/allergic conditions: Historical use included asthma, eczema, psoriasis, and rheumatoid arthritis, based on the known anti-inflammatory activity of corticosteroids.
6. Dosage Forms and Reported Dosages
Commercial supplements range from approximately 50 mg to 350 mg per capsule of processed glandular tissue. The following specific dosages have been documented in product disclosures and historical sources:
- One formulation provides 200 mg of whole adrenal glandular and 50 mg of adrenal cortex glandular, sourced from high-quality freeze-dried bovine tissue, per serving.
- Another product provides 100 mg of adrenal tissue (bovine, New Zealand, freeze-dried) per capsule.
- One practitioner-directed product suggests 2–4 capsules per day, in divided doses, between meals.
- Historical clinical use: In 1920, Muirhead devised a treatment for Addison's disease that required 1200 mg of dried adrenal (described as "1 part representing 5 parts fresh capsule").
No standardized dosage has been established by any regulatory authority or peer-reviewed clinical trial. This product should be used under the guidance of a qualified specialist who will be able to monitor cortisol levels and recommend dosage accordingly.
7. Safety Considerations and Interactions
Undeclared Hormones in Commercial Products
A significant and source-substantiated safety concern relates to the presence of active steroid hormones not declared on product labels. An analysis of the twelve most popular adrenal support supplements (six herbal, three bovine-derived, and three herbal-bovine combination formulas) found that all of the products contained small amounts of thyroid and steroid hormones (pregnenolone, budesonide, androstenedione, progesterone, cortisol, and/or cortisone) that were not listed as ingredients on their labels.
Small amounts (0.00000725 mg or less) of androstenedione, a hormone not legally permitted in dietary supplements, was found in two bovine-derived supplements. Six of the herbal formulas contained the thyroid hormone triiodothyronine (T3), as did all three of the bovine-derived products and all three herbal-bovine combination products. Amounts of T3 found in the products ranged from approximately 0.06 mcg to 1.3 mcg, which is relatively small compared to a typical prescription dose of 25 mcg to 75 mcg.
This finding was published in Mayo Clinic Proceedings (Akturk et al., 2018) and has direct implications for individuals taking thyroid medications or those with thyroid disease.
Bovine adrenal extracts may contain biologically active hormones at unpredictable concentrations, including cortisol and cortisol precursors, making their use potentially hormonally disruptive. These products carry meaningful risk without demonstrated benefit.
Gastrointestinal Effects
The most common side effect of adrenal extract is an upset stomach. Some preparations carry explicit instructions to take them with food to avoid gastrointestinal distress.
Injection Risk
Adrenal extract is unsafe when injected. There have been at least 50 reports of serious infection at the injection site. The injectable form of adrenal cortical extract was among the products targeted by FDA action.
Regulatory Status (FDA)
As a dietary supplement, bovine adrenal is not regulated by the FDA in the same manner as prescription drugs. The FDA does not review these products for safety or efficacy before they are marketed to consumers. This lack of oversight means there is no guarantee that the label accurately reflects the contents or potency of the supplement. The FDA has not reviewed adrenal extract for safety and effectiveness.
These products are usually advertised as safe despite limited or no data to support their efficacy or safety, and they are often taken without the supervision of a healthcare provider. Major concerns regarding unsupervised use result from the lack of rigorous assessment before distribution; such products may contain undeclared pharmaceuticals or unregulated hormones.
BSE and Prion Disease Risk
A significant concern involves the theoretical risk of transmitting prion diseases, such as Bovine Spongiform Encephalopathy (BSE), commonly known as "mad cow disease." BSE is a fatal neurological disease in cattle caused by infectious proteins called prions. While control measures have made classical BSE extremely rare, the possibility of contamination from animal-derived products remains a consideration.
The FDA has listed the adrenal gland among high-risk bovine tissues and tissue-derived ingredients in the context of BSE risk guidance. Although the Dietary Supplement and Health Education Act (DSHEA) allows the FDA to recommend the exclusion of high-risk animal tissues from dietary supplements, it does not allow their outright prohibition. Accordingly, the health food industry has no restrictions on the source of animal tissues used.
Risk of Masking Serious Conditions
The symptoms commonly labeled as adrenal fatigue—including exhaustion, sleep problems, difficulty concentrating, and salt or sugar cravings—overlap with dozens of well-established conditions: thyroid disorders, sleep apnea, depression, iron deficiency, and actual adrenal insufficiency (Addison's disease), among others. The concern from endocrinologists is that accepting an unproven diagnosis delays the identification of something treatable. A person with undiagnosed sleep apnea or hypothyroidism could spend months or years taking glandular supplements while the real problem goes unaddressed.
Potential HPA Axis Suppression
Although the cortisol content in typical glandular supplements is too low to cause clinical adrenal suppression (as noted above), another potential risk is that bovine adrenal supplements may contain active hormones, such as cortisol or thyroid hormones, even if not listed on the product label. Ingesting these exogenous hormones can interfere with the body's natural hormonal regulation.
Quality Assurance Considerations
Practitioners and sources recommend that if using adrenal glandulars, consumers should ensure that the supplier checks for pathogenic bacteria (total aerobic count, yeast, mold, Salmonella, E. coli, and S. aureus) and confirm that the tissue comes from a country without reports of BSE/TSE.
References
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