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Perennial ryegrass

Table of contents

Other Names

Almindelig rajgræsAnnual ryegrassAusdauernder LolchEnglish rye-grassEnglish ryegrassFestuca perennis (L.) Columbus & J.P.Sm.Hordeum compressum Boiss. & Orph.Italian ryegrassIvraie vivaceLolium aechicum RouvilleLolium agreste Roem. & Schult.Lolium annuum Bernh.Lolium annuum Gilib.Lolium brasilianum NeesLolium canadense Bernh.Lolium canadense Bernh. ex RouvilleLolium cechicum OpizLolium compressum Boiss. & Orph.Lolium compressum Boiss. & Orph. ex NymanLolium cristatum Pers.Lolium cristatum Pers. ex B.D.Jacks.Lolium felix RouvilleLolium glumosum PlanellasLolium gmelinii Honck.Lolium halleri C.C.Gmel.Lolium jechelianum OpizLolium latum RothLolium multiflorum var. ramosum Guss. ex Arcang.Lolium perenne L.Lolium perenne ssp. perenneLolium perenne var. cristatum Pers. ex B.D.Jacks.Lolium perenne var. perennePerennial rye grassRay grassRay-grass anglaisRyegrassWinter ryegrass

Synopsis

Perennial Ryegrass (Lolium perenne L.) as a Dietary Supplement and Natural Ingredient

1. Identity: Botanical Classification, Names, and Natural Source

1.1 Botanical Identity

Lolium perenne, known by the common names perennial ryegrass, English ryegrass, winter ryegrass, or ray grass, is a grass belonging to the family Poaceae. It is native to Europe, Asia, and northern Africa, but is widely cultivated and naturalised around the world.

The genus name "Lolium" originates from the Latin term for "darnel," a term used to refer to certain types of grasses, while the specific epithet "perenne" is derived from the Latin word for "everlasting" or "perennial," reflecting the plant's ability to grow back year after year.

The plant is a low-growing, tufted, and hairless grass with a bunching (tillering) growth habit. Its leaves are dark green, smooth and glossy on the lower surface, with untoothed parallel sides and prominent parallel veins on the upper surface; they are folded lengthwise in bud, with a strong central keel, giving a flattened appearance. Stems grow up to 90 cm.

The genus Lolium currently consists of 9–10 species worldwide, with six (or seven) taxa in the allogamous group — including L. perenne, L. multiflorum, L. rigidum, L. subulatum, L. loweii, and L. canariense — and three taxa in the autogamous group.

1.2 Distinguished from Related Species

Italian ryegrass (Lolium multiflorum) differs from perennial ryegrass in that each scale in the spikelet has a long bristle (awn) at the top, and its stem is round rather than folded.

1.3 Supplemental Forms and Preparations

As a dietary supplement ingredient, perennial ryegrass is used almost exclusively in the form of pollen extract rather than as a whole grass or leaf preparation. The pollen-derived material appears in two principal supplemental forms:

  • Standardized pollen extracts for prostate and menopausal conditions — commercially exemplified by Cernilton (also known as cernitin), which is a registered pharmaceutical product in Western Europe, Japan, Korea, and Argentina. Cernilton contains 60 mg of ryegrass pollen in a water-soluble fraction, with 3 mg of additional components in an acetone-soluble fraction per dose.
  • Sublingual and subcutaneous immunotherapy extracts — standardized pollen allergen extracts for allergen immunotherapy, most notably as a component of multi-grass pollen preparations. ORALAIR, for example, is a mixed allergen extract of five pollens including Perennial Rye (Lolium perenne L.) alongside Sweet Vernal, Orchard, Timothy, and Kentucky Blue Grass.

The whole vegetative plant (leaves, stems, seed) is used agriculturally as forage. The seed has historically been used as a cereal; it has a nutritional value similar to oats and contains gluten, though it has served as an emergency food used only when other sources fail.

2. Traditional and Historical Use

2.1 Agricultural and Fodder Use

Native to Europe, Asia, and northern Africa, perennial ryegrass has a long history of human use as a fodder grass, with the earliest records of its cultivation dating to the late sixteenth century in Europe. In Britain, it is recorded as being deliberately sown and cultivated for pasture as early as 1677.

Perennial ryegrass is the predominant forage grass in Europe and was brought to the United States for the same purpose — forage and lawns — and is also used for soil stabilization. Early European pastoralists introduced it to North America, where it was first recorded in Virginia in 1782, as well as to South America, Australia, New Zealand, and southern Africa to establish pastures and support livestock grazing.

The distribution and evolution of the genus has been affected by human involvement, which encouraged the spread of L. perenne and L. multiflorum as crops selected for forage and amenity characteristics.

It is a high-quality grazing grass characterized by fast growth, many tillers, and high digestible matter yields, and it has high nutritional value — being rich in protein, minerals, and vitamins.

2.2 Nutritional Use of the Seed

The seed of Lolium perenne has been used as a cereal; it has a nutritional value similar to oats and contains gluten, though it was considered an emergency food used only when other food sources failed, as the seed is rather small and fiddly to use.

2.3 Historical Note on Pollen Extract Use

There is no documented traditional or indigenous medicinal use of Lolium perenne pollen extracts in the ethnobotanical or historical literature predating modern pharmaceutical development. The use of ryegrass pollen extract as a therapeutic agent for prostate conditions and menopausal symptoms is a twentieth-century pharmaceutical development originating in Europe, particularly Scandinavia, and should not be classified as "traditional" in any ethnobotanical sense. The first controlled trials of Cernilton for urological conditions appeared in the European and Japanese literature from the 1970s onward.

3. Key Constituents and Active Compounds

3.1 Pollen Allergen Proteins

The most thoroughly characterized molecular constituents of Lolium perenne pollen are its allergenic proteins, classified by the World Health Organization/International Union of Immunological Societies (WHO/IUIS) nomenclature as Lol p allergens:

  • Lol p 1 (Rye I / group 1 allergen): The major allergen of L. perenne pollen is a glycoprotein of molecular weight approximately 27,000–32,000, known as Lol p 1 (Rye I), toward which 85–90% of grass-allergic patients are sensitive.
  • Lol p 2 (Rye II / group 2 allergen): The complete amino acid sequence of Lol p II was determined; the protein contains 97 amino acid residues, with a calculated molecular weight of 10,882, lacks cysteine and glutamine, and shows no evidence of glycosylation.
  • Lol p 3, Lol p 4, Lol p 5, and others: Purified pollen proteins contain major allergens (Lol p 1 and Lol p 5) and minor allergens (Lol p 11, Lol p 2, and Lol p 3).

In terms of population-level sensitization rates, in a stratified random sample of 320 white adults, the prevalence of puncture skin test positivity to Lolium perenne pollen extract was 16%, with 15% of all subjects classified as IgE antibody-positive to Lol p I, and 4% classified as positive to Lol p II.

3.2 Phytochemical Constituents of the Pollen Extract

The whole pollen extract used in supplements like Cernilton contains a broad spectrum of small molecules beyond the allergenic proteins. The extract contains 21 amino acids, various enzymes and coenzymes, and a high concentration of sterols; it also provides minerals, trace elements, and essential vitamins. In the acetone-soluble fraction, constituents include alpha-linolenic acid and phytosterols.

Research has identified specific bioactive small molecules proposed to explain pharmacological activity:

  • Cyclic hydroxamic acids: Rye pollen contains cyclic hydroxamic acid, which has been proposed to prevent the growth of prostate cells.
  • Phytosterols and flavonoids: Other identified compounds include stigmasterol and quercetin.
  • Isoflavones (in trace quantities): The pollen extract used in the Femal preparation has been shown to contain phytoestrogens, but HPLC analyses revealed only low, subeffective concentrations of daidzin, daidzein, and genistin; the extract showed no significant estrogenic activity in the immature rat uterotropic bioassay.
  • Norsesquiterpenes: Seven norsesquiterpenes have been isolated and identified from the whole plant of L. perenne, most of which exhibited potent allelopathic effects.

3.3 Fractionation of Cernilton Extract

The Cernilton formulation is defined by two fractions produced during processing: a water-soluble fraction (designated T60) and an acetone-soluble fraction (designated GBX). Each dose of Cernilton contains 60 mg of ryegrass pollen in the water-soluble fraction and 3 mg of components in the acetone-soluble fraction. The GBX fraction is generally considered to contain the lipid-soluble phytosterols and fatty acids (including alpha-linolenic acid) thought to be responsible for smooth muscle relaxation effects, while the T60 fraction contains water-soluble amino acids, enzymes, and other polar constituents.

4. Mechanisms of Action

4.1 Immunomodulatory Mechanism (Allergen Immunotherapy Context)

Allergen immunotherapy (AIT), first used more than a century ago, is an effective treatment in patients with seasonal allergic rhinitis. Allergen extract can be administered as subcutaneous or sublingual immunotherapy.

The precise mechanisms of action of allergen immunotherapy are not fully known. However, research using L. perenne peptide preparations has illuminated elements of the process. As an advantage over whole-protein allergens, peptides derived from ryegrass do not bind to IgE and cross-link FcεRI on the surfaces of mast cells and basophils, and therefore do not trigger the release of mediators such as tryptase and histamine.

Dose-dependent expression of CD63, a marker of basophil activation and degranulation, is observed in allergic patients when basophils are stimulated with L. perenne proteins. This stimulation is significantly greater than that induced by Lolium perenne peptides (LPP) at the same concentration, and a 100-fold higher LPP concentration was required to elicit basophil degranulation.

Allergen immunotherapy acts on the main cause of the allergic reaction by modifying or downregulating the immune response.

4.2 Proposed Mechanisms in Prostate and Urological Applications

Chemicals in rye grass pollen are proposed to decrease swelling and relax certain muscles, which might relieve symptoms of an enlarged prostate. However, the specific mechanism remains incompletely defined in the scientific literature. The chemical make-up of the extract is not fully known, nor is the mechanism of action clear, as noted by leading researchers in the field.

Preclinical and in vitro data have pointed to several candidate mechanisms:

  • Inhibition of the arachidonic acid cascade: Loschen and Ebeling (1991) described inhibition of the arachidonic acid cascade by rye pollen extract, which would suppress prostaglandin-mediated inflammation — a mechanism referenced in the RxList monograph for ryegrass.
  • Anti-inflammatory cytokine suppression: In isolated prostate tissue exposed to lipopolysaccharide, pollen extract showed dose-dependent inhibition of pro-inflammatory IL-6 and TNF-α gene expression, and was effective in preventing upregulation of catalase and SOD gene expression involved in antioxidant defense.
  • Inhibition of prostate cell growth: Chemicals in rye grass pollen might also slow the growth of prostate cancer cells. This is a preliminary in vitro finding and has not been confirmed in human trials.

4.3 Proposed Mechanisms in Menopausal Symptom Relief

The mechanism by which pollen extracts relieve vasomotor menopausal symptoms remains uncertain. Given that the pollen extract in the Femal preparation has been shown to be effective in the treatment of menopausal symptoms like hot flushes and sleeplessness, yet investigation revealed that any phytoestrogens present exist only at low, subeffective concentrations, the mechanism is considered non-estrogenic. A central or thermoregulatory mechanism has been postulated but not established.

5. Scientific Evidence by Area of Use

5.1 Benign Prostatic Hyperplasia (BPH)

Summary of Evidence: The clinical evidence for ryegrass pollen extract (Cernilton) in BPH is positive but modest in magnitude, limited by small sample sizes, short trial durations, and methodological gaps in the available controlled trials.

Key Systematic Review: A systematic review of Cernilton for BPH enrolled a total of 444 men across two placebo-controlled and two comparative trials lasting 12–24 weeks; three studies used a double-blind method, although the concealment of treatment allocation was unclear in all.

Key Double-Blind Placebo-Controlled Trial (1990): A double-blind, placebo-controlled study of rye grass pollen for BPH enrolled 60 patients awaiting operative treatment for outflow obstruction due to benign prostate enlargement in a 6-month study. There was a statistically significant subjective improvement with Cernilton at a dose of two tablets twice daily in 69% of patients, compared with 30% in the placebo group. In the treated group, there was also a significant decrease in post-voided urine and in the diameter of the prostate. However, differences in urine flow rate and voided volume were not statistically significant.

Cochrane Review Assessment: A 2002 Cochrane systematic review of rye grass pollen for BPH found human trials to be limited by short duration, limited numbers of enrollees, gaps in reported outcomes, and unknown quality of preparations. The authors concluded that the available evidence suggests rye grass pollen is well-tolerated and modestly improves urologic symptoms including nocturia. Additional randomized controlled trials were deemed necessary to evaluate long-term clinical effectiveness and safety. Wilt et al., in 2011, withdrew a planned update to the 2000 Cochrane review, citing a lack of adequate information to make a significant update.

Reported Dosage in Studies: The recommended daily dose of rye pollen referenced in the clinical literature is 80–120 mg of extract taken in two or three divided doses. The study dose used in the 1990 Buck et al. trial was 2 tablets of Cernilton twice daily. A dose of 126 mg of a specific rye grass pollen extract taken three times daily has also been reported for BPH.

Evidence Strength: Weak to moderate. Results are consistently favorable for subjective symptom improvement (especially nocturia), but effect sizes are modest, trials are small, and objective urodynamic outcomes (flow rate, voided volume) were not consistently improved.

5.2 Chronic Prostatitis and Chronic Pelvic Pain Syndrome (CP/CPPS)

Rye-pollen extract (Cernilton) showed promising results in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in a preliminary, placebo-controlled study from Germany.

The pollen extract has also shown efficacy in men with inflammatory prostatitis and chronic pelvic pain syndrome, improving total symptoms, pain, and quality of life without significant side effects.

One trial enrolled 139 men in a prospective, placebo-controlled, randomized study of pollen extract in patients with inflammatory chronic prostatitis and chronic pelvic pain syndrome.

Evidence Strength: Preliminary. The available trials are small, and further replication in larger, well-designed RCTs is required before strong conclusions can be drawn.

5.3 Allergic Rhinoconjunctivitis (Grass Pollen Allergy) — Immunotherapy

This is the area for which Lolium perenne-derived material has the strongest and most robust clinical evidence, particularly in the context of allergen immunotherapy (AIT) formulations.

Sublingual Immunotherapy (SLIT) — ORALAIR: ORALAIR is an allergen extract indicated as immunotherapy for the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis, confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies. It is approved for use in persons 5 through 65 years of age.

Recommended use is in a pre-coseasonal regimen, starting daily treatment approximately 4 months before the start of the pollen season, with treatment continued daily throughout the season; treatment should continue for 3–5 years. Clinical efficacy and safety of ORALAIR in patients with grass pollen-induced allergic rhinitis has been demonstrated in a comprehensive clinical development program of randomized controlled trials. Effectiveness has been substantiated in subsequent observational studies, with sustained efficacy following treatment cessation and favorable adherence, quality of life, benefit, and satisfaction for patients.

3-Year RCT Evidence: In a pivotal trial, the mean adjusted average daily symptom score (AAdSS) was reduced by 36.0% and 34.5% at season 3 in the 2-month and 4-month pre- and coseasonal active treatment groups, respectively, compared with the placebo group (P < 0.0001 for both).

Observational Study (883 patients): Data from 883 patients (children, adolescents, and adults) were analyzed; the highest-ranked patient needs referred to having less allergic rhinitis symptoms, being able to go outdoors, and being free in the choice of leisure activities. Most patients (89.2–94.6%) attained at least minimally relevant benefit.

Sublingual Immunotherapy — Efficacy (2-Year Trial, PubMed): In a two-year study, 54 patients suffering from seasonal rhinoconjunctivitis (with or without asthma) were allocated to either 6-month preseasonal SLIT with Lolium perenne extract (n=35) or to a control group (n=19), followed by a 9-month pre-coseasonal SLIT period. During the first pollen season, treated patients needed significantly less medication than controls (p < 0.05). In the second season, former control subjects also required fewer drugs (p < 0.01). The treated patients showed significantly less intraseasonal eosinophil cationic protein (ECP) than a reference set of grass-allergic individuals. The authors concluded that Lolium perenne SLIT is well tolerated and reduces medication requirements during pollen season while also reducing eosinophil activation.

Subcutaneous Peptide Immunotherapy (LPP): A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) with a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. A Phase IIb, prospective, double-blind, placebo-controlled, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170, or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3, and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks, and after completion.

Evidence Strength: Strong. Multiple large, well-designed, placebo-controlled RCTs and regulatory approval in Europe (23 countries) and the United States (FDA) support the use of L. perenne-containing SLIT preparations for allergic rhinoconjunctivitis.

5.4 Menopausal Vasomotor Symptoms

A purified and specific cytoplasmic pollen extract (PSCPE) preparation containing Lolium perenne pollen — marketed as Femal — has been evaluated in clinical trials for menopausal symptoms.

Key RCT (Winther et al.): A study aimed to evaluate whether Femal, a herbal remedy made from pollen extracts, alleviates the symptoms of the menopause, especially hot flushes. The design was a randomized, double-blind, placebo-controlled, parallel trial of 64 menopausal women, of whom 54 completed the trial. This trial showed that 65% of women treated with purified and specific cytoplasmic pollen extract experienced a decrease in hot flashes compared with only 38% of the placebo group.

Larger Trial (n=417): In a trial of 417 menopausal women taking two Femal tablets per day for 84 days, a significant effectiveness of purified and specific cytoplasmic pollen extract was observed on vasomotor symptoms (hot flushes and sweats), and a significant improvement in quality of life, irritability, and fatigue as assessed by a questionnaire and visual analogue scales.

Multiple Trials Overview: The efficacy of purified and specific cytoplasmic pollen extract in the treatment of menopausal symptoms has been demonstrated in several clinical trials, most conducted comparing the extract to placebo, showing a significant decrease in hot flushes, insomnia, depression, irritability, and fatigue after 12 weeks of treatment, with minimal side effects.

Evidence Strength: Preliminary to moderate. The evidence base is limited by a small number of trials, and at least one review notes that there is only one RCT testing pollen extracts in menopausal women. The non-estrogenic mechanism of action remains unexplained, and the evidence base does not yet meet the threshold for established clinical recommendation by major menopause societies.

6. Body Systems and Health Areas Associated with Perennial Ryegrass

  • Immune / Allergic system: L. perenne pollen is one of the most clinically significant grass pollen allergens worldwide. Ryegrass (Lolium perenne) pollen is a common cause of seasonal allergic diseases affecting an increasing part of the world population. In supplement/therapeutic context, standardized extracts are used as allergen immunotherapy to desensitize the immune system.
  • Urological / Prostate: Rye grass pollen extract is used for prostate conditions such as benign prostatic hyperplasia (BPH), prostate pain, and ongoing swelling of the prostate.
  • Endocrine / Menopausal: Purified cytoplasmic pollen extract (PSCPE) has been evaluated for vasomotor menopausal symptoms including hot flushes, sweating, insomnia, irritability, and fatigue.
  • Gastrointestinal: Rye grass fiber has been proposed to increase the growth of healthy bacteria in the gut, though there is no good scientific evidence to support these uses.
  • Cardiovascular / Lipid metabolism: Alpha-linolenic acid identified in the acetone-soluble fraction of pollen extracts is an omega-3 fatty acid of broad nutritional interest, but specific cardiovascular trials using ryegrass pollen extract have not been conducted.

7. Dosage Forms and Reported Dosages

7.1 Oral Pollen Extract Supplements (BPH / Prostatitis)

  • A dose of 2 tablets of Cernilton twice daily was used in the 1990 double-blind BPH trial.
  • The daily dose referenced in the clinical literature is 80–120 mg of extract taken in two or three divided doses.
  • 126 mg of a specific rye grass pollen extract three times daily has been reported for BPH.

7.2 Oral Pollen Extract Supplements (Menopausal Symptoms)

  • A dose of two Femal tablets per day for 84 days was studied in a trial of 417 menopausal women.

7.3 Sublingual Immunotherapy Tablets (ORALAIR)

  • ORALAIR is available as a sublingual tablet in a strength of 100 IR (equivalent to approximately 3000 BAU — bioequivalent allergy units).
  • A dosage of 300 IR in the five-grass pollen tablet equates to approximately 20–25 μg/mL of the group-five major allergens.

7.4 Subcutaneous Peptide Immunotherapy (LPP/gpASIT+â„¢)

  • In the Phase IIb trial, cumulative doses of 70, 170, or 370 μg LPP were administered via weekly subcutaneous injections, with active treatment groups reaching their assigned doses within 2, 3, and 4 weeks, respectively.
  • A 6-week dose-escalation protocol involved 61 grass pollen-allergic patients receiving 2 subcutaneous injections of LPP once weekly for 6 weeks.

8. Safety, Adverse Effects, and Interactions

8.1 Pollen Extract in BPH/Prostatitis (Oral Use)

Rye grass pollen is well tolerated for oral use. Adverse events are rare and mild; only rare gastrointestinal symptoms or allergic skin reactions have been reported.

8.2 Sublingual Immunotherapy (ORALAIR)

Adverse reactions reported in more than 5% of ORALAIR patients included oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, asthma, oropharyngeal pain, tonsillitis, and oral paresthesia.

In case of oral inflammation or wounds, treatment with ORALAIR should be stopped to allow complete healing of the oral cavity.

Patients should be informed of the signs and symptoms of severe allergic reactions and instructed to seek immediate medical care and discontinue therapy should any of these occur.

8.3 Subcutaneous Peptide Immunotherapy (LPP)

During LPP treatment trials, all adverse events were mild or moderate and resolved without corrective therapy. The frequency of adverse events of special interest (especially headache) was greater in the LPP/DnaK combination group.

The first patient who received LPPs experienced anaphylaxis at the first injection of 50 μg. After this event, the treatment schedule was revised and the initiation dose was reduced to 5 μg; the new revised treatment schedule was tolerated by all subsequent patients.

In a subsequent safety study, no fatality, serious adverse event, or epinephrine use was reported. Mean wheal diameters after injections were less than 0.6 cm and mean redness diameters less than 2.5 cm, independent of dose.

8.4 Cross-Reactivity

Because of the extensive cross-reactivity of allergenic components of grass pollen from different species, L. perenne allergen can be used to treat allergic rhinitis induced by other grasses. Conversely, individuals sensitized to other grass species may display IgE reactivity to L. perenne proteins.

8.5 Contraindications for Immunotherapy Formulations

The FDA-approved labeling for ORALAIR lists a history of any severe systemic allergic reaction or severe local reaction to sublingual allergen immunotherapy as contraindications to its use.

8.6 Evidence Limitations

Further placebo-controlled trials are needed to evaluate the real efficacy of pollen extract in BPH-related lower urinary tract symptoms. Additional randomized placebo and active-controlled trials are needed to evaluate the long-term clinical effectiveness and safety of Cernilton rye pollen extract.

References

Health Conditions

Health conditions that Perennial ryegrass may help support.

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Body Systems

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Perennial ryegrass | Vitabase