ALFALFA LEAF

BACKGROUND

Ingredient Type: Botanical

Also Known As: Medicago sativa, Greek alfalfa, Lucerne, Purple medick

Medicago sativa Linn., also known as Alfalfa leaf, hails from the legume family but is considered an herb. It is a flowering perennial that closely resembles its cousin, the clover. Referred to as the “father of all foods,” alfalfa is the most cultivated legume in the world (1). Known as one of the most productive species of legumes, alfalfa is also a widely adapted forage species referred to as the “queen of forages” (14). Originally cultivated as livestock feed, it also was grown for purposes of improving soil and a long history of medicinal uses for humans as a supplement. In addition, its seeds can be sprouted for alfalfa sprouts that can be found in most grocery stores.

While containing merely eight calories per one cup, alfalfa is high in vitamin K, vitamin C, copper, folate, and manganese. Major phytoconstituents of alfalfa include saponins, flavonoids, alkaloids, amino acids, phytosterols, coumarins, phytoestrogens, and digestive enzymes (1). Alfalfa also contains vitamin A, vitamin B1, vitamin B6, vitamin E, and is rich in protein, carotene, potassium, zinc, calcium, and iron (3). Another compound found in alfalfa is the amino acid, canavanine, which constitutes approximately 2% of the weight of fresh sprouts. However, during germination of the sprouts, most of it is converted into other amino acids. Canavanine is also found in raw alfalfa seeds (7).

TRADITIONAL USES

With limited research having been conducted on the benefits of alfalfa in humans, historical references for medicinal uses are limited; however, current research is now being conducted on the health benefits of this plant. There is a history of alfalfa uses in traditional Ayurvedic medicine primarily as an aid for digestive system disorders, central nervous system disorders, and other various ailments (1).

Reports have documented alfalfa as being used to help improve memory, ease kidney pain and cough, and help soothe aching muscles. In China, it was used to treat fever, kidney stones, and reduce swelling. It was also used to cleanse the blood, liver, and bowels and treat arthritis as well as whooping cough. Some of its benefits were curing both kidney problems and auto-immune disorders (3). In early American medicine, it was used to help relieve urinary and bowel problems, treat arthritis, cancer, and scurvy (1).

WHAT DOES SCIENCE TELL US?

Alfalfa Possibly has Antimicrobial Properties:

In a few studies, there have been multiple endophytic fungi found in the roots, stems, and leaves of alfalfa. In one study, the isolated fungi were studied for their antimicrobial potential against other pathogenic fungi and pathogenic bacteria and their ability to produce extracellular oxidative enzymes (9). Of the six endophytic fungi that were isolated from alfalfa, Aspergillus ochraceus (MSEF6) was found to inhibit the growth of all the pathogenic fungi (C. algicans, Aspergillus flavus, Fusarium oxysporum, Fusarium solani, and Fusarium sp.) and the pathogenic bacteria, Bacillus cereus. As it was the first time that antimicrobial properties were characterized from A. ochraceus MSEF6, this was a novel discovery. A. ochraceus MSEF6 also was found to contain structurally diverse metabolites, including phenolics, quinones, benzofurans, and isochromosomes. After screening this isolated fungus for additional properties, namely its ability to produce extracellular oxidative enzymes, A. ochraceus MSEF6 displayed important peroxidase activity as well as the production of laccase enzyme. These discoveries indicate that the endophytic fungus A. ochraceus MSEF6 is a promising agent in producing a supply of natural antimicrobial enzymes (9).

Alfalfa Possibly Helps Support Healthy Cholesterol Levels:

Very few human studies have been conducted on the benefits of alfalfa seed on lowering high cholesterol, but in the few trials conducted and the results have been promising. It is believed the saponins in alfalfa are the attributing compound that helps to lower cholesterol levels. One small study of three subjects that increased their alfalfa seed intake to 160 grams a day for three weeks showed a total blood cholesterol level decrease without any toxic side effects (10).

In one study, fifteen patients with hyperlipoproteinemia (HLP) were observed to see if there was a connection with alfalfa seed consumption and lowered cholesterol. Both total plasma cholesterol and low-density lipoprotein (LDL) cholesterol were observed. The study participants consumed 40 grams of alfalfa seeds three times a day for an eight-week test period with a total daily consumption of 120 grams of alfalfa seeds per day. Three types of HLP were included in the study: Type IIA, IIB, and IV, each with varying degrees of results. Participants with type IIA (n = 8) had the most significant results, with a lowered total plasma cholesterol of 17% going from 9.58 to 8.00 mmol/1 (P < 0.001). Their LDL cholesterol dropped 18% going from 7.69 to 6.33 mmol/1 (P < 0.01). Overall, the maximum decrease in total cholesterol was 26%, and the maximum decrease in LDL cholesterol was 30%. With these decreases in these types of cholesterol, researchers believe that there is a strong correlation between alfalfa seed consumption and normalizing of cholesterol concentrations in people with type II HLP disorder (2).

In an animal study, the saponins found in alfalfa were shown to decrease cholesterolemia, essentially reducing the total cholesterol/high-density lipoprotein-cholesterol ratio. The saponins reduced intestinal absorption of cholesterol, increased fecal excretion of bile acids, and decreased the percent distribution of fecal deoxycholic and lithocholic acids (11).  In this placebo-controlled study, eight monkeys were fed an alfalfa leaf protein prepared from a low-saponin cultivar semi-purified food. These monkeys were selected for their plasma cholesterol levels that were similar to those observed in adults from the U.S. There were no adverse side effects of toxicity in the monkeys during the six to eight-week study. The results of this study suggest that the saponins found in alfalfa might be an active agent in treating patients with hypercholesterolemia (11).

Another animal study investigated the effects of alfalfa seed extract and its potential to lower blood cholesterol levels. For this placebo-controlled animal study, thirty healthy adult rabbits were divided into groups of six with varying degrees of 50% ethanolic alfalfa seed extract consumption and 500 mg a day of cholesterol for a cycle of 45 days leading to a full 90-day period. After taking blood samples on day 45 and day 90 of the experiment, increased serum cholesterol and LDL cholesterol were shown to have reduced by 38 – 41.7% and 48 – 53.3% respectively in the rabbits that were fed with alfalfa seed extract. The positive effects of decreased intestinal absorption of endogenous cholesterol and an increase in bile acid excretion are attributed to the high saponin content in alfalfa (12).

Extracts of alfalfa contain high concentration levels (157 +/- 6 ng/g) of an immune-reactive hormone-like material that releases thyrotropin (IR-TRH) (13). Thyrotropin is a hormone produced by the pituitary gland. It responds to signals sent from the hypothalamus gland, which is why it’s known as the thyroid-stimulating hormone. When compared to synthetic thyrotropin, the alfalfa TRH has shown to have a higher retention time. Scientists are still trying to understand the mechanism of action and the biological function of the material TRH in alfalfa (13).

In another animal study, monkeys were fed a semi-purified diet that included 1.2 mg of cholesterol/Cal for six months. The purpose of this study was to study the effects of alfalfa on atherosclerosis in the aorta and the coronary arteries. The monkeys were divided into three groups and fed food with the addition of cholesterol with or without alfalfa meal. In the monkeys that were taking the alfalfa, cholesterolemia and plasma phospholipid levels were decreased. The distribution of plasma lipoproteins was normalized, and the aortic and coronary atherosclerosis was reduced (15).

Alfalfa Possibly has Antioxidant Properties:

Alfalfa has been researched and shown promise for its ability to reduce apoptosis and other cell damage caused by free radicals. Unfortunately, these studies have all been conducted on animals with few-to-none conducted on humans. There are still significant enough positive results from the few animal studies that warrant a mention of alfalfa’s potential as having antioxidant properties. One in vitro study that tested alfalfa extract for their antioxidant activity implicated that the mechanism of action may be attributed to alfalfa’s ability to inhibit or scavenge the ABTS radicals. The purpose of this study was to investigate the alcoholic extract of M. sativa for its antioxidant activity through various models; ABtS radical scavenging, iron chelating activity, DPPH radical scavenging, lipid peroxidation assay, nitric oxide scavenging assay, and alkaline DMSO assay. Multiple concentrations of the alcoholic extract of M. sativa (ranging from 2 to 1,000 μg/ml) were tested in these different assays, and it was found that all of the free radicals that were introduced into the test compounds were scavenged completely in a concentration-dependent manner. The authors concluded that the high levels of polyphenols found in the extracts of alfalfa were what exhibited the plant’s high antioxidant activity of scavenging free radicals, including various pathophysiology of diseases as well as aging; and that the extract of alfalfa is effective against free radical-mediated disease (5).

According to scientists who have conducted multiple animal studies on alfalfa and its antioxidant effects, alfalfa has been effective for CNS disorders, heart and metabolic disorders, and as a digestive aid. In multiple in vivo and in vitro studies conducted on rats with cytotoxicity, a concentration of alfalfa reduced reactive oxygen species production and enhanced reduced glutathione, both pathways that reduce DNA fragmentation and prevent apoptosis pathways by interrupting mitochondrial respiratory chain and single oxidation/reduction reactions. Essentially, alfalfa can neutralize reactive oxygen species, thus reducing cell death and DNA damage caused by free radicals (4).

Alfalfa Possibly Helps Support Women’s Health:

The phytoestrogens found in alfalfa are of great interest to scientists looking for an alternative to commercial hormone replacement treatment. One study looked at the effects of alfalfa and sage extracts for the treatment of hot flashes in menopausal women. Many symptoms of menopause, including insomnia, night sweating, headaches, and dizziness, are reflections of the body’s reaction to experiencing estrogen deprivation. This deprivation affects multiple central neurotransmitters in the body. The researchers in this study wanted to conduct a trial to see if an alternative route could be taken to reduce menopausal symptoms by using plant extracts instead of commercial hormone replacement. Thirty women experiencing menopausal symptoms participated in the three-month study, where they were administered both alfalfa and sage extracts. All thirty women completed the study with the majority showing a significant reduction in their hot flushes and night sweating, with twenty of the participant’s symptoms disappearing completely. In four of the women, the night sweats showed good improvement, and in the remaining six women, there was a total reduction in their night sweating. There were no reported side effects, and the conclusion was made that alfalfa extract can contribute to the reduction of menopausal symptoms, especially hot flushes and night sweating (6).

Alfalfa Possibly Supports Healthy Blood Sugar Levels:

In a study performed on mice, it was determined that the use of alfalfa extract in the diet and drinking water lowered blood sugar levels through the mechanism of increasing the release of insulin from the pancreas of the mice. The alfalfa extract was added to the diet (62.5 g/kg) and the drinking water (2.5 g/L) of streptozotocin-diabetic mice with hyperglycemia. The aqueous extract of alfalfa (1mg/mL) was shown to stimulate 2-deoxy-glucose transport by nearly 2-fold. It also was shown to stimulate glucose oxidation 1.7-fold and increased incorporation of glucose into glycogen by 1.6 fold. The aqueous extract of 0.25 – 1 mg/ml alfalfa was administered in 20-min test increments. The extract was shown to evoke a 2.5 to 6.3-fold stimulation in the secretion of insulin from the pancreas. The extract was found to be heat-stable and alkali (0.1 m-HCI and NaOH). Overall, the results indicate that alfalfa exhibits traditional anti-diabetic potential as an antihyperglycaemic agent and also demonstrated the same insulin-releasing and insulin-like activity as other anti-diabetic drugs (17).

In one four-week study conducted on the potential of alfalfa sprouts to mitigate the hyperlipidemic and hyperglycemic activity caused by diabetes, alfalfa seemed to have significant benefits when compared to conventional diabetic drugs. This particular animal study focused on streptozotocin-induced diabetes that was performed via injection of 55 mg/kg of streptozotocin (STZ). The test subjects were divided into groups with varying doses of methanolic extract (500 mg/kg), petroleum ether (32.5 mg), and butanol extracts (60 mg), along with two additional groups receiving metformin and rosuvastatin. Also, there was a control group and an STZ-induced group. After four weeks, there was a significant decrease (P>0.05) in triglycerides, total cholesterol, low-density lipoproteins, and very-low-density lipoproteins when compared with the conventional drug rosuvastatin. Overall, the alfalfa sprouts supplementation decreased high levels of total VLDL and LDL cholesterol in diabetic-induced animals showing potential as an agent in treating diabetes (16).

SAFETY

Interactions:

A major drug interaction is with Warfarin. The high levels of vitamin K in alfalfa could pose a possible risk for those taking blood thinners like Warfarin. Vitamin K helps the blood clot, and Warfarin is used to slow blood clotting. Using these two in combination can cause a decrease in the effectiveness of Warfarin (18).

Moderate drug interactions with alfalfa include birth control pills. Due to its estrogen content, there could be interactions with those who are taking an estrogen replacement, particularly those taking birth control pills, and for those who are nursing, pregnant, or trying to get pregnant (19,20).

Moderate drug interactions with alfalfa include diabetic medication (antidiabetes drugs). Alfalfa may decrease blood sugar, and thus taking in combination with diabetic medication might cause blood sugar to go to low (19).

Alfalfa has been known to increase the immune system, which can decrease the effectiveness of medications that are meant to decrease the immune system. This moderate interaction includes the drugs azathioprine, basiliximab, cyclosporine, daclizumab, and muromonab-CD3 (19).

Another moderate interaction is with medications that can cause increased sensitivity to sun exposure. When taken in large doses, alfalfa might increase sensitivity to sunlight, which in combination with another drug that effectively has the same reaction, could increase sunburn, blistering, and rashes (19).

Side-Effects:

There have not been many reported side effects with the consumption of alfalfa. However, there also have not been many studies performed on humans and their interaction with the consumption of alfalfa.

Alfalfa might cause a reaction that closely resembles lupus. L-Canavianine (LCN) is an amino acid that is found in legumes. It constitutes approximately 2% of the weight of fresh sprouts and, in high doses, has been shown to effectively block DNA synthesis in vitro within 24 hours, demonstrating an ability to induce a lupus erythematosus-like syndrome in mice (Prete, 1985).

In one in vitro study on human immunoregulatory cells, the dose-dependent administration of LCN inhibited the action of T-suppressor cells in human peripheral blood mononuclear cell cultures (8).

Heavy consumption of alfalfa over a long period may cause red blood cells to break down, which can cause serious issues (3).

REFERENCES

1. Bora KS, Sharma A. Phytochemical and pharmacological potential of Medicago sativa: a review. Pharm Biol. 2011;49(2):211-20. doi: 10.3109/13880209.2010.504732.
2. 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(1-2):173-9. DOI: 10.1016/0021-9150(87)90019-0.
3. Alfalfa. https://www.homeremediesweb.com/alfalfa_health_benefits.php. Accessed, March 8, 2020.
4. Sadeghi L, Tanwir B, Yousefi Babadi VY. Antioxidant effects of alfalfa can improve iron oxide nanoparticle damage: Invivo and invitro studies. Regulatory Toxicology and Pharm. 2016; 81: 39-46. Doi: 10.1016/j.yrtph.2016.07.010.
5. Rana MG, Katbamna RV, Padhya AA, Dudhrejiya AD, et al. In Vitro Antioxidant and Free Radical Scavenging Studies of Alcoholic Extract of Medicago Sativa L. Rom. J. Biol. – Plant Biol. 2010: 55(1); 15-22. 
6. De Leo V, Lanzetta D, Cazzavacca R, Morgante G. Treatment of neurovegetative menopausal symptoms with a phytotherapeutic agent. Minerva Ginecol. 1998 ;50(5):207-11.
7. Prete PE, Effects of L-canavanine on immune function in normal and auto-immune mice: disordered B-cell function by a dietary amino acid in the immunoregulation of auto-immune disease. Can. J. Physiol. Pharmacol. 1985;63(7):843-54. DOI: 10.1139/y85-139.
8. Alcocer-Varela J, Iglesias A, Llorente L, Alarcón-Segovia D. Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa. Arthritis Rheum. 1985;28(1):52-7. DOI: 10.1002/art.1780280109.
9. Attia E, Farouk H, Abdelmohsen UR, El-Hatatny MH. Antimicrobial and extracellular oxidative enzyme activities of endophytic fungi isolated form alfalfa (Medicago sativa) assisted by metabolic profiling. South African J. Botany. 2019. Doi: 10.1016/j.sajb.2019.12.003.
10. Malinow MR, McLaughlin P, Stafford C. Alfalfa seeds: Effects on cholesterol metabolism. Experientia. 1980; 36: 562-563. DOI: 10.1007/BF01965801.
11. Malinow MR, Connor W E, McLaughlin P, Stafford C, et al. Cholesterol and bile acid balance in Macaca fascicularis. Effects of alfalfa saponins. J. Clin. Invest. 1981; 67(1): 156-162. doi: 10.1172/JCI110008.
12. Dixit VP, Jain P. Hypolipidaemic Effects of Medicago Sativa Seed Extracts (50% EtOH) in Rabbits Under Experimental Conditions. Anc. Sci Life. 1990;10(1):52-5.
13. Jackson IM. Abundance of immunoreactive thyrotropin-releasing hormone-like material in the alfalfa plant. Endocrinology. 1981;108(1):344-6. DOI: 10.1210/endo-108-1-344.
14. Diseases of the Alimentary Tract-Ruminant. Veterinary Medicine. 2017; 11 ed. Ch. 8: 175-435. Doi: 10.1016/B978-0-7020-5246-0.00008-5.
15. Malinow MR, McLaughlin P, Naito HK, et al. Effect of alfalfa meal on shrinkage (regression) of atherosclerotic paques during cholesterol feeding in monkeys. Atherosclerosis. 1978; 30 (1): 27-43. Doi: 10.1016/0021-9150(78)90150-8.
16. Seida A, El-Hefnawy H, Abou-Hussein D, Mokhtar FA, Abdel-Naim A. Evaluation of Medicago sativa L. sprouts as antihyperlipidemic and antihyperglycemic agent. Pak. J. Pharm Sci. 2015;28(6):2061-74.
17. Gray AM, Flatt PR. Pancreatic and extra-pancreatic effects of the traditional anti-diabetic plant, Medicago sativa (lucerne). Br. J. Nutr. 1997;78(2):325-34. DOI: 10.1079/bjn19970150.
18. Mousa SA. Antithrombotic effects of naturally derived products on coagulation and platelet function. Methods. Mol. Biol. 2010;663:229-40. doi: 10.1007/978-1-60761-803-4_9.
19. Alfalfa. https://www.rxlist.com/alfalfa/supplements.htm. Accessed June 24, 2020.
20. Jones T. Alfalfa. https://www.healthline.com/nutrition/alfalfa. Accessed June 24, 2020.