Mu Xu

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Medicago sativa L.

Not yet clinically reviewed

Genus: Medicago Species: sativa Pinyin: Mu Xu
Alfalfa苜蓿

Traditionally used for

  • Ears & hearing
  • Digestion
  • Urinary & fluids
  • Energy & fatigue
  • Liver & jaundice

Cautions & contraindications

  • Bleeding disorders
Moderate evidence · 3 studies

☯ TCM Properties

Category: clearing heat
Temperature: neutral
Taste: bitter
Meridians: spleen, stomach, kidney
Functions:

Clears Damp-Heat; Clears Heat from the Spleen and Stomach; Promotes Urination; Promotes Urination and Reduces Edema; Expels Urinary Stones

Traditional Chinese Uses

Mu Xu (alfalfa herb) is a cool, bitter herb used in Chinese medicine to clear Damp-Heat, promote urination, and relieve edema. It has been used historically for urinary complaints, jaundice, and night blindness. While not among the most commonly used herbs in classical formulas, its nutritive qualities — it is rich in vitamins and minerals — have given it relevance in dietary therapy for deficiency conditions and as a general tonic for vascular and metabolic health.

Western Herbalism Properties

Actions:
tonicdiureticalterative

Traditional Uses

The Costanoan used Medicago sativa as an ear medicine (Bocek, 1984). The Keres employed it for unspecified medicinal purposes (Swank, 1932). It was additionally documented as fodder and as a food spice by the Navajo, Okanagan, and Shuswap (Moerman, 1998).

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Botanical Description

Medicago sativa, alfalfa or lucerne, is a deep-rooted perennial herbaceous legume in the family Fabaceae, believed native to central and southwestern Asia and the eastern Mediterranean, and now cultivated worldwide as one of the most important forage crops. The plant produces a stout, woody taproot that can penetrate 4-5 m into the soil, allowing it to access deep moisture. The aerial stems reach 30-90 cm tall and are erect to ascending, much-branched, and slightly hairy. The alternate, trifoliolate leaves bear obovate, finely toothed leaflets 1-3 cm long, with the terminal leaflet stalked. Short axillary racemes of papilionaceous flowers appear in summer, with corollas typically violet to purple, occasionally yellow or variegated, 6-12 mm long. The fruit is a tightly coiled, spiraled, hairy pod 5-6 mm in diameter, containing several small kidney-shaped yellow-brown seeds. The species fixes atmospheric nitrogen through symbiosis with Sinorhizobium meliloti.

Active Constituents

L-Canavanine

Non-protein amino acid (L-arginine antimetabolite, guanidinooxy analogue)

Concentration: 1.3-2.4% of the dry matter of commercially grown sprouts and 1.4-1.8% of the seed (mean 1.54%); much lower in the mature aerial herb, which is the part used as Mu Xu

An L-arginine antimetabolite that is mischarged onto arginyl-tRNA and incorporated into protein in place of arginine, yielding structurally aberrant canavanyl proteins. In human lymphocyte culture it reduces the mitogenic response and abolishes concanavalin A-induced suppressor-cell function, with a consequent rise in IgG release and anti-DNA binding activity, and it reactivated an SLE-like syndrome in macaques. It is the constituent responsible for the autoimmune signal attached to alfalfa seed, sprout and tablet products.

Phylloquinone (vitamin K1)

Naphthoquinone (fat-soluble vitamin)

Concentration: Concentrated in the green leaf; content varies widely with crop, season and whether the material is leaf meal or sprout, and is not standardised in commercial alfalfa tablets

Serves as the cofactor for gamma-glutamyl carboxylase in hepatic synthesis of clotting factors II, VII, IX and X. Because alfalfa leaf is a rich and unstandardised source, it is the constituent behind the herb's documented antagonism of coumarin anticoagulants.

Coumestrol

Coumestan (isoflavonoid phytoestrogen)

Concentration: Rises sharply in stressed, fungally infected or sprouting material rather than being fixed for the species

Binds oestrogen receptors with appreciable affinity and is the compound behind the classical reports of infertility in sheep grazed heavily on Medicago and Trifolium forage. Its clinical relevance at human dietary or decoction doses is unquantified.

Medicagenic acid glycosides (alfalfa saponins)

Triterpenoid (oleanane) saponin

Concentration: Highest in the root; leaf and aerial parts contain less

Surface-active triterpene glycosides that complex sterols in cell membranes and in the gut lumen. They are haemolytic in vitro, bind dietary cholesterol and bile acids, and account for the bitterness and the gastrointestinal upset seen with large quantities of alfalfa material.

⚠ Drug Interactions

Warfarin and other coumarin/vitamin K antagonist anticoagulants

Moderate Evidence: Probable

Alfalfa leaf is a concentrated source of phylloquinone, which restores the gamma-carboxylation of clotting factors that warfarin blocks by inhibiting vitamin K epoxide reductase. The interaction is pharmacodynamic and dose-dependent on the vitamin K actually delivered. The practical problem is that phylloquinone content in alfalfa leaf tablets and teas is neither declared nor consistent between batches, so the size of the antagonism cannot be predicted or dosed around.

Clinical note: Do not start or stop alfalfa leaf products during warfarin, acenocoumarol or phenprocoumon therapy without checking the INR. If the patient insists on continuing, keep the intake fixed day to day and re-titrate the anticoagulant against INR rather than trying to eliminate the herb intermittently.

Immunosuppressive and immunomodulatory therapy in SLE and related autoimmune disease (e.g. prednisone, hydroxychloroquine, azathioprine)

Major Evidence: Probable

L-canavanine in alfalfa seed, sprout and tablet material dysregulates T-cell immunoregulation: in vitro it abolishes concanavalin A-induced suppressor-cell function and increases IgG and anti-DNA release from human lymphocytes. Feeding alfalfa seeds or sprouts induced an SLE-like haematological and serological syndrome in cynomolgus macaques, and L-canavanine sulfate alone reactivated that syndrome in previously affected animals. In humans, pancytopenia has been reported during ingestion of alfalfa seeds and an SLE exacerbation has been reported after ingestion of alfalfa tablets. This is the plant working directly against the goal of the drug therapy rather than a pharmacokinetic interaction.

Clinical note: Treat alfalfa seed, sprout and tablet products as contraindicated in anyone with SLE, drug-induced lupus, a positive ANA with autoimmune symptoms, or a history of autoimmune haemolytic anaemia, irrespective of what other treatment they are on. Canavanine sits mainly in the seed and young sprout, so seed-derived tablets are the highest-risk presentation. Separately, raw sprouts carry a documented Salmonella and E. coli O157 risk that matters more in patients on immunosuppressants.

Medicago polymorpha L. (nan mu xu) supplied as Mu Xu

Moderate Evidence: Established

Chinese materia medica define Mu Xu as the aerial parts of either Medicago sativa L. (zi mu xu) or Medicago polymorpha L. (nan mu xu), the latter being the material commonly gathered and sold in central and southern China and the lower Yangtze. Almost all of the toxicological literature - the canavanine quantification, the macaque SLE model and the human case reports - was generated on M. sativa. M. polymorpha is a separate annual species whose canavanine and phylloquinone content has not been characterised to the same standard, so neither the lupus signal nor the warfarin signal can be assumed to transfer at the same magnitude in either direction.

Clinical note: Establish which Medicago the supplier is providing before relying on any of the published safety figures. Apply the SLE and warfarin cautions to both species by default, since the absence of data on M. polymorpha is not evidence of its absence of canavanine.

Oestrogen replacement therapy, oral contraceptives and tamoxifen

Theoretical Evidence: Theoretical

Coumestrol from alfalfa is a receptor-binding phytoestrogen, established as the cause of clover and Medicago forage infertility syndromes in sheep. No human pharmacokinetic or pharmacodynamic interaction study with hormonal therapy has been published, and the coumestrol exposure delivered by a therapeutic dose of Mu Xu has not been quantified, so this remains an inference from the constituent rather than an observed interaction.

Clinical note: Mention it, but do not present it as an established interaction. There is no human data on which to base a dose adjustment.

Evidence Tier

Moderate evidence · 3 studies

Recorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.

Systematic review / meta-analysis

0

Randomized controlled trial

0

Other clinical trial

0

Observational / case report

0

Other / unclassified

1

1 verified · 0 unverified

Show the study

Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description

Clinical Studies

Systemic Lupus Erythematosus-Like Syndrome in Monkeys Fed Alfalfa Sprouts: Role of a Nonprotein Amino Acid

Malinow MR, Bardana EJ Jr, Pirofsky B, Craig S, McLaughlin P (1982) Science animal Verified: In vitro / animal

Cynomolgus macaques fed alfalfa sprouts developed haematological and serological abnormalities resembling human systemic lupus erythematosus. In animals in which the syndrome had already been induced by alfalfa seeds or sprouts, L-canavanine sulfate on its own reactivated it, identifying the non-protein amino acid rather than the whole plant matrix as the responsible agent. This is the primary experimental basis for treating alfalfa as contraindicated in lupus.

Effects of L‐canavanine on t cells may explain the induction of systemic lupus erythematosus by alfalfa

Alcocer-Varela J, Iglesias A, Llorente L, Alarcón-Segovia D (1985) Arthritis & Rheumatism in vitro

L-canavanine exerted dose-related effects on human immunoregulatory cells in culture, diminishing the mitogenic response and abrogating concanavalin A-induced suppressor-cell function, with an accompanying increase in the release of IgG and of DNA-binding activity. The authors proposed this loss of suppressor-cell control as the mechanism linking alfalfa ingestion to lupus induction in humans.

Role of non-protein amino acid l-canavanine in autoimmunity

Akaogi J, Barker T, Kuroda Y, Nacionales DC, Yamasaki Y, Stevens BR, Reeves WH, Satoh M (2006) Autoimmunity Reviews systematic review Verified: Other / unclassified

A review of the evidence connecting dietary L-canavanine from alfalfa and other legumes to autoimmune phenomena, covering the arginine-antagonist mechanism, incorporation into aberrant canavanyl proteins, the primate SLE model and the human reports. It provides the mechanistic framework practitioners need for the alfalfa-lupus caution, while noting that the canavanine dose required in humans has never been established.

Historical Texts

Ming Yi Bie Lu

Han to Southern and Northern dynasties (compiled c. 500 CE by Tao Hongjing)
Records Mu Xu as bitter in taste, neutral in nature and non-toxic, governing calming of the centre and benefiting the person, and states that it may be eaten over a long period. This is the earliest materia medica entry for the drug and establishes it as a food-grade item rather than a strong medicinal, which is why classical dosing offers no guidance on the toxicological limits identified in the modern literature.

Ben Cao Gang Mu

Ming dynasty (1596)
Li Shizhen classes Mu Xu among the vegetables and records that the plant came originally from Dayuan (Ferghana) and was brought back to China by the Han envoy Zhang Qian. He gives its actions as benefiting the five viscera, lightening the body, washing evil heat qi from between the spleen and stomach, and freeing the small intestine of malign heat toxin - the clearing-damp-heat and promoting-urination functions still attached to the drug.

Shi Liao Ben Cao

Tang dynasty (early 8th century, Meng Shen)
Meng Shen treats Mu Xu as a dietary therapy item: it calms the centre and benefits the five viscera, washes away evil qi lodged between the spleen and stomach and the various malign heat toxins, and may be boiled with fermented bean paste or made into a soup. This is the source of the damp-heat and stomach-heat indications carried in the modern functions.

References

  1. Rosenthal GA, Nkomo P. The Natural Abundance Of L-Canavanine, An Active Anticancer Agent, in Alfalfa, Medicago Sativa (L.) . Pharmaceutical Biology (2000) [DOI]
  2. Malinow MR, Bardana EJ Jr, Goodnight SH Jr. PANCYTOPENIA DURING INGESTION OF ALFALFA SEEDS . The Lancet (1981) [DOI]
  3. Roberts JL, Hayashi JA. Exacerbation of SLE Associated with Alfalfa Ingestion . New England Journal of Medicine (1983) [DOI]

This information is for educational purposes only and is not intended to replace professional medical advice. Always consult a qualified healthcare provider before using any herbal remedy, especially if you are pregnant, nursing, or taking medications.

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