Alfalfa may lower cholesterol levels but raw seeds and sprouts contain a toxin, canavanine. Canavanine has been associated with systemic lupus erythematosus (SLE) and pancytopenia.

[LFODPKM ] Letter Key

Latin Name

Medicago sativa

Family

Leguminosae (Fabaceae)

Other Common Names

Chilean clover, lucerne, buffalo grass

Description

• A deep-rooted, perennial fodder plant; its sprouts are used as food.
• Whole herb or leaves are most used medicinally.

Part Used

Seed, sprouts, stem, leaves

Known Active Constituents

• Canavanine, a nonprotein amino acid, is found mainly in the raw seed and sprouts. Phenolic compounds include coumestrol; alfalfa seeds are reported to contain stachydrine and L-homostachydrine (1).
• Alfalfa also contains saponins (glycosides of soya sapogenols) and esterified bidesmosides and tridesmosides of acidic oleanenes (medicagenic acid, 16-hydroxymedicagenic acid, and hederagenin) (2).

Mechanism/Pharmacokinetics

• Alfalfa appears to inhibit the gastrointestinal absorption of cholesterol.
• Pharmacokinetics have not been delineated.
• Canavanine, a toxin, is structurally similar to arginine; by competing for receptors, it may inactivate arginine-containing enzymes (3). Canaline, a metabolite of the ornithine analog canavaline, may inhibit pyridoxal phosphate and associated enzymes. It is possible that the substitution of L-canavanine for arginine in proteins results in targeting of abnormal proteins by the immune system, resulting in autoantibody production (4). L-canavanine abrogates concanavalin A-induced suppressor cell function in vivo in a dose-dependent manner; in immunoregulatory cells from normal subjects and those with SLE, L-canavanine increased release of IgG and DNA-binding activity (5); it also decreased mitogenic response to phytohemagglutinin and concanavalin A (but not pokeweed mitogen).

[Outline]

• LLatin Name
• FFamily
• OOther Common Names
• DDescription
• PPart Used
• KKnown Active Constituents
• MMechanism/Pharmacokinetics

[CAO ] Letter Key

Clinical Trials

• Hypercholesterolemia
  • Fifteen patients with type II hyperlipoproteinemia were given 40 g of heat-treated alfalfa seeds t.i.d. with meals for 8 weeks. Total cholesterol fell 17%, from 9.58 to 8.0 mmol/L (p < 0.001) and low density lipoprotein (LDL) cholesterol fell 18% from 7.69 to 6.33 mmol/L (p < 0.01). Apolipoprotein B decreased 34%, from 2.17 to 1.43 g/L (p < 0.05); there was no change in apolipoprotein A-1 (6).

Animal/In Vitro

• Hypercholesterolemia
  • Alfalfa hay in the diet or partially hydrolyzed saponins from alfalfa hay prevented hypercholesterolemia and atherosclerosis in cholesterol-fed monkeys; alfalfa seeds decreased hypercholesterolemia and atherosclerosis in cholesterol-fed rabbits (1,7).
• Antifungal effect
  • Alfalfa root saponins have specific antifungal effects and are active against various forms of Candida, Torulopsis, (8) and Cryptococcus neoformans (9) in vitro. A liposomal dosage form of compound G2 (the gluco derivative of medicagenic acid) conferred a survival advantage in mice infected with Cryptococcus neoformans (9). A topical preparation of the gluco derivative of medicagenic acid was effective in curing skin lesions of guinea pigs infected with Trichophyton mentagrophytes (9).

Other Claimed Benefits/Actions

• Diabetes
• Arthritis
• Cancer
• Boils
• Urinary problems
• Bowel problems
• Ulcers
• Vitamin deficiency
• Debility
• Menses induction
• Heart disease
• Halitosis
• Hypothrombinemic purpura

[Outline]

• CClinical Trials
  • Hypercholesterolemia
• AAnimal/In Vitro
  • Hypercholesterolemia
  • Antifungal effect
• OOther Claimed Benefits/Actions

[AT ] Letter Key

Adverse Reactions

• Pancytopenia
  • Pancytopenia has been observed in a 59-year-old man who was ingesting large amounts of alfalfa saponins (up to 160 g daily) as part of a cholesterol-lowering study (10).
• SLE
  • Two women with quiescent SLE experienced reactivation after long-term consumption of alfalfa tablets (11). In the first case, a 40-year-old woman with a 26-year history of SLE developed symptoms 9 months after consuming 15 alfalfa tablets daily (her disease had been clinically inactive for at least 4 years). In the second case, a 50-year-old woman with a 25-year history of mild SLE associated with membranous glomerulonephritis (she had been in remission for an unspecified period) developed rising antinuclear antibody (ANA) and cryoglobulins and progressive hypocomplementemia; renal biopsy showed diffuse proliferative glomerulonephritis. She had been ingesting eight tablets daily for 2 1/2 years. Although these cases are scantily documented, they are plausible, given other clinical reports and animal studies (12).
  • Four patients developed a reversible SLE-like syndrome (symptoms included arthralgias, myalgias, and rash) with positive ANA (solid pattern) after consuming 12 to 24 alfalfa tablets daily for 3 weeks to 7 months.
• Uric acid effects
  • Serum urate levels increased from 296 to 336 µmol/L in patients receiving 120 g heat-treated alfalfa seeds per day in a cholesterol-lowering trial (6). Alfalfa may contain purines that can precipitate a gout attack in susceptible individuals.
• Dermatologic reactions
  • Six cases of pruritic, patchy, erythematous eruptions have been reported associated with the use of alfalfa seeds in capsules or teas (1).
• Other symptoms
  • Ingestion of more than 120 g seeds/day can cause gastrointestinal symptoms (flatulence, diarrhea, abdominal discomfort, and anorexia) (1).

Animal Toxicity

• L-canavanine sulfate reactivated SLE-like symptoms in cynomolgus monkeys previously exposed to alfalfa seeds (4).
• L-canavanine is toxic in rats, mice, and lower organisms. Long-term consumption of partially hydrolyzed dietary alfalfa hay saponins (1% to 1.2% of diet) was not toxic to monkeys (1).
• Estrogenic effects have been reported in cattle consuming large amounts of alfalfa as fodder (1).

[Outline]

• AAdverse Reactions
  • Pancytopenia
  • SLE
  • Uric acid effects
  • Dermatologic reactions
  • Other symptoms
• TAnimal Toxicity

Common Dosage Forms

• Dried herb: 5 to 10 g t.i.d. in capsules or as infusion.
• Liquid extract: [1:1 in 25% ethanol (EtOH)] 5 to 10 mL t.i.d.

• Is the consumption of alfalfa sprouts safe?
• Can alfalfa toxins be rendered safe?

Q: Is the consumption of alfalfa sprouts safe?

A: Limited consumption of alfalfa sprouts in salads and sandwiches is probably nothing to worry about, but daily ingestion should be avoided. Patients with autoimmune diseases should avoid alfalfa sprouts altogether.

Q: Can alfalfa toxins be rendered safe?

A: Yes, by cooking; avoiding raw seed and sprouts is key. Heat appears to denature toxic components of alfalfa while preserving antihypercholesterolemic effects (13).

Although there is certainly a case to be made for further study of alfalfa’s lipid-lowering effects, other components of alfalfa may also be problematic (the mechanism behind the single case of pancytopenia is unclear).

1. De Smet PAGM. Medicago sativa. Adverse effects of herbal drugs, vol 1. Berlin: Springer-Verlag, 1992:161–169.
2. Bruneton J. Pharmacognosy: phytochemistry medicinal plants, 2nd ed. Secaucus NJ: Lavoisier Springer-Verlag, 1999:715–716.
3. Herbert V, Kasdan TS. Alfalfa, vitamin E, and autoimmune disorders. Am J Clin Nutr 1994;60:639–642.
4. Malinow MR, Bardana EJ, Pirofsky B et al. Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid. Science 1982;216:415–417.
5. Alcocer-Varela J, Iglesias A, Llorente L et al. Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa. Arthritis Rheum 1985;28:52–57.
6. Mölgaard J, von Schenck H, Olsson AG. Alfalfa seeds lower low density lipoprotein cholesterol and apolipoprotein B concentrations in patients with Type II hyperlipoproteinemia. Atherosclerosis 1987;65:173–179.
7. Malinow MR, McLaughlin P, Kohler GO et al. Prevention of elevated cholesterolemia in monkeys by alfalfa saponins. Steroids 1977;29:105–110.
8. Polacheck I, Zehavi U, Naim M et al. Activity of compound G2 isolated from alfalfa roots against medically important yeasts. Antimicrob Agents Chemother 1986;30:290–294.
9. Zehavi U, Polacheck I. Saponins as antimycotic agents: glycosides of medicagenic acid. In: Waller GR, Yamasaki K, eds. Saponins used in traditional and modern medicine. New York: Plenum, 1996:535–546.
10. Malinow MR, Bardana EJ, Goodnight SH. Pancytopenia during ingestion of alfalfa seeds. Lancet 1981;i:615.
11. Roberts JL, Hayashi JA. Exacerbation of SLE associated with alfalfa ingestion. N Engl J Med 1983;308:1361.
12. Prete PE. The mechanism of action of L-canavanine in inducing autoimmune phenomena. Arthritis Rheum 1985;28:1198–2000.
13. Malinow MR, McLaughlin P, Bardana EJ et al. Elimination of toxicity from diets containing alfalfa seeds. Food Chem Toxic 1984;22:583–587.