IngredientsBovine spleen (also known as Rate Bovine, Extrait de Rate, Extrait Splénique, Spleen Concentrate, Spleen Factors, Raw Spleen, Hydrolyzed Spleen Extract, or Predigested Spleen Extract) refers to the spleen organ tissue of Bos taurus (domestic cattle). Spleen extract is produced from animal spleens; the spleen's main functions are to break down and remove old and damaged red blood cells and to provide white blood cells to fight infection. As a supplement ingredient, it is most often identified simply as "bovine spleen" or "grass-fed beef spleen" on product labeling.
Spleen extracts are made from the spleens of cows, pigs, or other animals for use as supplements. The dominant commercial form is a freeze-dried and desiccated whole-tissue powder, typically encapsulated in vegetarian capsules. The freeze-dried, non-defatted, and desiccated process aims to preserve the nutrient profile. Some manufacturers produce hydrolyzed or predigested spleen extracts, in which enzymatic digestion is applied prior to drying in order to pre-cleave peptide bonds and concentrate bioactive peptides. The process of extracting splenopentin from spleen involves enzymatic digestion of larger proteins found in the tissue, which allows researchers to obtain and study this specific peptide.
Products are available as whole-tissue capsules, peptide-concentrated extracts, powders for mixing, and as components in multi-organ "ancestral" supplement formulas. Pharmaceutical-grade bovine spleen extracts are currently quite popular in Germany for the treatment of infectious conditions and as immune-enhancing agents in cancer.
Glandular therapy involves the administration of extracts produced from specific organs or glands of animals. Its use 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 is that oral ingestion of an animal gland — such as the liver, spleen, or thyroid — will strengthen the function of the corresponding gland in humans.
Glandular therapy was first taken seriously by physicians in the 19th century, when it was discovered that dried porcine thyroid gland could treat underactive thyroid and dried animal-based adrenal glands could treat Addison's disease. Before this, neither condition was controllable. As the years passed, doctors tried other glands with varying rates of success: ovaries for infertility and menopause, testicles for faltering male sex drive, thymus for the immune system, and pancreas for digestion. Later, research moved well beyond glands. Concentrated spleen was tried for anemia, heart for cardiac diseases, lung for pulmonary conditions.
Bovine spleen emerged in 20th-century glandular therapy as a way to nourish and support the human spleen and immune system, particularly in patients with chronic fatigue, low immunity, or blood disorders. In the 1930s, spleen extract was shown to improve white blood cell counts as well as benefit infections such as malaria and typhoid fever, while in modern-day Germany, spleen extract has become popular for its immune-potentiating effects in treating infection and cancer.
Cytotrophic bovine spleen extracts have historically been taken by people with allergic reactions (hives, canker sores, cold blisters), lymph node swelling, blood concerns (anemia, lymphocytosis), demineralization accompanied by hyperirritability, as well as those with lowered resistance to infections and boils.
According to Pizzorno and Murray, spleen extract may be used for immune conditions ranging from immune potentiation, infection, cancer, celiac disease, dermatitis herpetiformis, ulcerative colitis, rheumatoid arthritis, glomerulonephritis, systemic lupus erythematosus (SLE), vasculitis, low white blood cell counts, and thrombocytopenia.
However, as pharmaceutical usage exploded in the mid-1900s, glandulars went out of fashion, and researchers were no longer interested in investigating their usefulness. A wide variety of glandular materials have been used medicinally, such as brain, hypothalamus, spleen, aorta, intestine, and parathyroid.
The scientific basis for the use of animal glandulars is that they contain hormones, hormone precursors, and an array of nutrients such as vitamins, minerals, and amino acids required for healthy organ function. In addition to providing nutrients, glandulars are thought to have organ-sparing properties: by supplying exogenous hormones and hormone precursors, they allow rest and recovery of the overburdened organ.
The spleen may contain naturally occurring vitamins such as vitamin B12, selenium, riboflavin (vitamin B2), and heme iron. Heme iron, which is the form of iron bound within hemoglobin and myoglobin, is generally considered more bioavailable than non-heme iron from plant sources. The most abundant lipid classes in spleen tissue are phospholipids (phosphatidylethanolamine, phosphatidylcholine), free cholesterol, and triacylglycerols.
The most extensively characterized bioactive compound uniquely associated with spleen tissue is tuftsin, a tetrapeptide with the amino acid sequence L-threonyl-L-lysyl-L-prolyl-L-arginine (Thr-Lys-Pro-Arg). Discovered by Victor Najjar in 1970 at Tufts University, tuftsin is the natural activator of phagocytic cells including macrophages, monocytes, neutrophils, and microglial cells. It is generated through sequential cleavage by splenic tuftsin endocarboxypeptidase and leukokininase.
Tuftsin is a natural immune-modulating tetrapeptide derived from the proteolytic degradation of the 289–292 amino acid residues of IgG in the spleen, and was described as a phagocytosis-stimulating factor. Tuftsin was named for Tufts University where the tetrapeptide was discovered. It is activated in the spleen and bound to a carrier leukokinin molecule, a gamma-globulin that coats the polymorph. Tuftsin is absent in splenectomized humans and dogs, and its absence after splenectomy leads to problems with infection.
The tetrapeptide tuftsin (Thr-Lys-Pro-Arg) stimulates phagocytosis by blood neutrophilic granulocytes and tissue macrophages in a highly specific manner. Tuftsin is cleaved off the carrier γ-globulin molecule as the free active form by two enzymes — one in the spleen and the other on the outer membrane of the phagocyte.
Tuftsin stimulates macrophages that have taken up residence in specific tissues like the liver, spleen, and lymph nodes. Tuftsin also helps mobilize other white blood cells to fight infection.
A second major family of spleen-specific bioactive peptides centers on splenin and its derived synthetic analog splenopentin. The only structural difference between the splenic product (splenin) and thymopoietins I and II, both of bovine origin, is the substitution of Glu for Asp at position 34. The biologically active synthetic peptide splenopentin (SP-5) corresponds to positions 32–36 of splenin, with the sequence Arg-Lys-Glu-Val-Tyr.
Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Arg-Lys-Asp-Val-Tyr) are synthetic immunomodulating peptides corresponding to the region 32–34 of splenin and thymopoietin, respectively. Thymopoietin (TP) was originally isolated as a 5-kDa (49-amino acid) protein from bovine thymus while studying effects of thymic extracts on neuromuscular transmission and was subsequently observed to affect T cell differentiation and function.
Splenopentin acetate is a synthetic pentapeptide derived from the active region of splenin, a thymic and spleen-associated peptide. It plays a crucial role in immune modulation by enhancing T-cell differentiation and immune response regulation.
The spleen represents the largest accumulation of lymphoid tissue in the body. Splenic macrophages play an important role in the presentation of antigen to lymphocytes. Pathogens that enter the substance of the spleen are engulfed by macrophages and presented to immunologically active cells, which in turn induce antibody production from the germinal centres. The spleen is also the site of opsonin production — proteins that bind to foreign antigens and enhance the uptake and phagocytosis of bacteria.
Both immunological stimulatory and inhibitory activities have been detected in a bovine spleen extract prepared by acetic extraction of an acetonic powder. When fractionated by ultrafiltration, two successive ultrafiltrates of molecular weight less than 10,000 are obtained: fraction U1, which contains the largest pool of low-molecular-weight substances, and U2, which is enriched in an immunosuppressive peptide. This finding illustrates that raw spleen extracts contain a complex mixture of both pro- and anti-inflammatory signaling molecules simultaneously.
Tuftsin's primary biological function is the stimulation of phagocytosis. Research demonstrated that tuftsin enhances the tumoricidal capacity of macrophages, increasing their ability to kill tumor cells in vitro in a dose-dependent manner. This antitumor activity is mediated through both direct cytotoxic mechanisms (nitric oxide, reactive oxygen species) and enhanced antigen presentation to adaptive immune cells.
Tuftsin activates phagocytosis and oxidative burst without triggering the full inflammatory cytokine cascade that LPS induces, making it potentially safer for therapeutic immune enhancement. Compared to recombinant G-CSF and GM-CSF (clinical myeloid growth factors), tuftsin activates existing phagocytes rather than stimulating new cell production, providing faster onset but shorter duration of immune enhancement.
Structure-activity relationship studies revealed that Pro3 and Arg4 are the most critical residues for phagocytosis-stimulating activity. Thr1 can be modified with less impact, while Lys2 contributes to receptor binding affinity.
Splenopentin plays a crucial role in immune modulation by enhancing T-cell differentiation and immune response regulation, and is primarily studied for its potential in treating immune deficiencies, autoimmune disorders, and infections by stimulating thymocyte activity.
In animal research, the recovery of immunocompetence in mice following sublethal irradiation was shown to be enhanced by the splenopentin analog DAc-SP-5. The treatment effects were verified by splenic plaque-forming response to a T-cell–dependent antigen and in the hematopoietic colony-forming assay.
Small splenic peptides (SSPs) of whole spleen extract efficiently suppress the development of psoriatic arthritis in vivo, even in the presence of sustained levels of pro-inflammatory cytokines. SSPs target dendritic cells and convert them into tolerogenic cells, which in turn differentiate naïve CD4+ cells into Foxp3-expressing T regulatory cells (Tregs). This process requires direct contact between SSP-activated DCs and naïve CD4+ T cells via PD-1 and CTLA4 immune checkpoint receptors of T cells.
A fundamental and unresolved question is whether these peptide constituents survive intact after oral ingestion. Studies on bioactive peptides show mixed survival rates after digestion, with many degraded before reaching the bloodstream. While the spleen is rich in certain nutrients and peptides and contains factors involved in immune function, there is insufficient evidence that these components survive digestion or have meaningful immunological effects when ingested. Research on isolated or injected tuftsin and splenopentin cannot be directly extrapolated to orally administered freeze-dried bovine spleen tissue.
While spleen supplements are often promoted as immune boosters and blood-building aids, there is no direct human clinical evidence to validate these claims. There are no published randomized controlled trials evaluating freeze-dried spleen capsules for immune enhancement, red blood cell production, or athletic performance in humans. Most cited "evidence" comes from in vitro studies or animal research that cannot be directly applied to supplement use in people.
The most scientifically relevant human-oriented evidence relates not to oral supplementation, but to the biology of tuftsin deficiency. Tuftsin is an endogenous tetrapeptide that stimulates phagocytosis and is released from the Fc fragment of IgG by a splenic endocarboxypeptidase. Tuftsin activity and splenic function were measured in 21 patients with AIDS, 7 patients with AIDS-related complex (ARC), 22 patients who had undergone splenectomy, and 37 healthy volunteers. There was a significant inverse correlation between tuftsin activity and splenic function in all subjects. Tuftsin activity was significantly lower in patients with AIDS, ARC, and in those who had undergone splenectomy compared with healthy volunteers. Tuftsin deficiency may contribute to the risk of bacterial infection in symptomatic HIV-positive individuals. These findings pertain to endogenous tuftsin production, not to oral supplementation.
At the preclinical level, a German-language study (Volk et al., Arzneimittelforschung 1991) investigated immunorestorative properties of hydrolysates and ultrafiltrates of bovine spleen in an experimental context. Volk HD, Eckert R, Diamantstein T, and Schmitz H published on the immunorestitutive action of hydrolysates and ultrafiltrates of bovine spleen in Arzneimittelforschung 1991;41:1281–5. This study examined laboratory-based restoration of immune parameters and represents early-phase evidence that cannot by itself establish clinical efficacy in humans.
There is limited meaningful scientific evidence to indicate spleen extracts offer any benefits. Only double-blind, placebo-controlled studies can show a treatment effective, and only a handful of small-scale studies of this type have been reported for spleen extracts. Many published studies on oral use of spleen glandular extracts date back to the 1930s and do not remotely reach current scientific standards. Some studies have evaluated injected extracts of spleen, but these findings are not likely to apply to the oral product.
The most scientifically grounded rationale for spleen supplementation involves its theoretical use as a source of replacement peptides following splenectomy. Tuftsin is absent in splenectomized humans and dogs. Its absence after splenectomy leads to problems with infection. Congenital familial deficiency of tuftsin with a history of repeated and severe infections has been observed in at least 4 families.
Congenital tuftsin deficiency usually arises when the peptide is mutated to an inactive peptide. The acquired type occurs if the spleen function is curtailed by removal or disease. Tuftsin deficiency is manifested by severe recurrent infections involving primarily the skin, lymph nodes, and lungs. Spleen extract is given "as replacement therapy" in cases where the spleen has been surgically removed or isn't working properly. However, whether oral bovine spleen extracts meaningfully restore circulating tuftsin levels or mimic endogenous splenic function has not been established in human clinical trials.
There is emerging but highly preliminary preclinical evidence relating to autoimmune conditions. The major challenge in the treatment of autoimmune diseases is the restoration of impaired peripheral immune tolerance. Small splenic peptides (SSPs) of whole spleen extract efficiently suppress the development of psoriatic arthritis in vivo, even in the presence of sustained levels of pro-inflammatory cytokines. SSPs target dendritic cells and convert them into tolerogenic cells, which in turn differentiate naïve CD4+ cells into Foxp3-expressing T regulatory cells (Tregs). This study was conducted in a mouse model. A clinical study of the synthetic splenopentin analog (DA SP-5) in patients with psoriatic arthritis was reported (Greiner et al., Dermatol Monatsschr 1990), with therapeutic use of splenopentin (DA SP-5) investigated in patients with psoriasis arthropathica. This represents a very small, early-phase investigation and does not constitute robust clinical evidence.
Bovine spleen is marketed for iron support in part due to its heme iron content. Anemia, debility, fatigue, pernicious anemia, and general blood support have been listed as traditional uses for spleen supplementation. No peer-reviewed randomized controlled trial has been identified that specifically tests oral bovine spleen supplements for iron-deficiency anemia in humans as of the available evidence.
One small study indicated that spleen extract may be effective in supporting patients with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). This is described as a single, small-scale investigation without the design characteristics necessary to establish efficacy.
Other conditions that may benefit from supplementation with spleen extract include replacement therapy after spleen removal, treatment of kidney disease, blood disorders, ulcerative colitis, and vasculitis, and as an adjunct therapy for patients undergoing cancer treatment. These proposed uses are based on the known biology of splenic immune function, the immunostimulatory properties of isolated peptides such as tuftsin, and historical clinical observation rather than controlled clinical trials of oral bovine spleen supplements.
Research demonstrated that tuftsin enhances the tumoricidal capacity of macrophages, increasing their ability to kill tumor cells in vitro. This antitumor activity is mediated through both direct cytotoxic mechanisms (nitric oxide, reactive oxygen species) and enhanced antigen presentation to adaptive immune cells. These in vitro and animal findings have not been translated into human clinical trials of oral bovine spleen supplementation.
The overall body of human clinical evidence for oral bovine spleen supplementation is weak. Scientific research directly supporting the use of bovine spleen supplements for immune system support is very limited. There are no large-scale clinical trials or robust studies demonstrating clear benefits of consuming bovine spleen for immune enhancement in humans. Most published research concerns the isolated peptides tuftsin and splenopentin administered by injection in animal models or in vitro systems. There is no clinical evidence showing that taking spleen in capsule or powder form produces the claimed benefits in humans. Most of what is promoted is based on animal studies, nutrient charts, or anecdotal reports — not peer-reviewed, controlled human trials.
Based on the composition of bovine spleen tissue and the biochemistry of its identifiable constituents, bovine spleen as a supplement is associated with the following body systems:
Bovine spleen supplements are sold primarily as capsules containing freeze-dried whole-tissue powder. In the commercial market, capsule sizes commonly provide 500 mg of desiccated bovine spleen per capsule.
It should be noted that none of these dosages are derived from randomized controlled clinical trials of oral bovine spleen supplementation. They are manufacturer recommendations. No pharmacopeial monograph or government body has established a recommended daily intake or therapeutic dose for oral bovine spleen preparations.
The most significant, source-documented safety concern for bovine spleen supplements is the theoretical risk of transmissible spongiform encephalopathy (TSE) — specifically bovine spongiform encephalopathy (BSE, or "mad cow disease"). There is concern about contamination of spleen extract from sick or diseased animals. In particular, spleen extract might theoretically cause or transmit BSE if obtained in countries where BSE has been reported. While this side effect has not been reported in humans from supplement use, it is recommended to avoid using spleen extract from countries where BSE has been reported.
The FDA issued an interim final rule to prohibit the use of certain cattle material, to address the potential risk of BSE, in human food including dietary supplements and cosmetics. Prohibited cattle materials include specified risk materials, small intestine of all cattle, material from nonambulatory disabled cattle, material from cattle not inspected and passed for human consumption, and mechanically separated beef.
In some TSEs, deposits of abnormal prion proteins are detected in other nervous and non-nervous tissues, such as the spinal cord, peripheral nerves, intestine, spleen, lymph nodes, and bone marrow. This is relevant because spleen is explicitly identified as a tissue in which prion accumulation has been observed in the context of TSE, warranting vigilance regarding the geographic sourcing of bovine spleen products.
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 and allows preservation of cell materials for a longer time. Concerns for transmission of BSE require that tissues be procured only from countries and herds free of this disease.
The World Organisation for Animal Health classifies the United States as "negligible risk" for BSE, based on the country's history with the disease (only seven cases from 2003 to 2023), control measures in place, and a robust BSE surveillance system.
Bovine spleen is an animal-derived product. Individuals with known beef, bovine protein, or meat allergies may experience allergic reactions. Those with beef or bovine-derived ingredient allergies should avoid use.
When taken by mouth, it is not known if spleen extract is safe or what the side effects might be. No side effects or adverse effects have been reported with the use of oral spleen preparations in published literature as of the available records, though this statement reflects the absence of formal safety studies rather than a confirmed clean safety record.
People use spleen extract for conditions such as low white blood cell counts, cancer, autoimmune diseases, and infections, but there is no good scientific evidence to support these uses.
In the United States, bovine spleen is marketed as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. The FDA has issued rules to prohibit the use of certain cattle materials to address the potential risk of BSE in human food, including dietary supplements. Bovine spleen, provided it originates from animals inspected and passed for human consumption and does not constitute a "specified risk material" (such as brain or spinal cord from older animals), is generally considered permissible under current FDA regulations when sourced appropriately.
It is noteworthy that raw bovine spleen extracts appear to contain both immunostimulatory and immunosuppressive fractions simultaneously. When injected into mice sensitized with sheep red blood cells, three distinct activities were detected: one fraction was inhibitory at the sensitization period; at the last step of differentiation of the lymphocyte, the same fraction was stimulatory at low dose and inhibitory at large dose. This last activity was attributed to the presence of an immunosuppressive peptide. The clinical significance of these dual effects in humans consuming oral preparations is unknown.
Health conditions that Bovine spleen may help support.
Bovine spleen is among the most concentrated food sources of heme iron, which is essential for hemoglobin synthesis and addressing iron-deficiency anemia. Traditional healers directed spleen consumption at blood and anemia-related conditions. While heme iron bioavailability is clinically established, no human trials specifically test bovine spleen supplements as an anemia intervention.
Spleen extracts, and tuftsin in particular, have been studied in animal autoimmune disease models including experimental autoimmune encephalomyelitis. Traditionally, spleen was given for autoimmune-related immune dysregulation. Evidence is restricted to preclinical studies; no human clinical data support bovine spleen supplementation for autoimmune conditions.
Iron and B12 deficiencies are recognized contributors to chronic fatigue, and bovine spleen is exceptionally rich in both nutrients as well as heme iron. Traditional practice directed spleen consumption toward debility and low energy states. No clinical trial data confirm bovine spleen supplementation for chronic fatigue as a defined condition.
Spleen extracts have been used historically to support resistance to infection including common respiratory illnesses. Tuftsin stimulates macrophage-mediated innate immunity relevant to bacterial and viral pathogens. This is a traditionally documented use with preclinical biological plausibility, but no human clinical trials support efficacy against colds or influenza.
Iron-deficiency fatigue arises when inadequate iron impairs oxygen transport and cellular energy production. Bovine spleen's exceptional heme iron content makes it a plausible dietary intervention for this symptom. The link is grounded in well-established heme iron nutrition science, though bovine spleen supplement-specific clinical trials for fatigue are absent.
Bovine spleen extracts have historically been used for immune reconstitution after illness, and splenopentin has been studied in animal models for restoring leukocyte and immune function after depletion. The traditional application of spleen feeding for recovery from debilitating conditions is documented. No clinical trials confirm this for oral supplementation.
Tuftsin, a peptide derived from splenic processing of IgG, stimulates macrophage and natural killer cell activity relevant to antiviral innate immunity. Tuftsin deficiency has been documented in AIDS patients. These are preclinical and associational findings; no clinical trials have tested bovine spleen supplements specifically for viral immune responses.
Body systems that Bovine spleen may help support.
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