Fenugreek

Fenugreek is a product sometimes processed into breads, and sometimes supplemented. It can make urine and sweat smell of maple syrup. It also appears to be a libido enhancer, anti-diabetic and is pretty healthy; many people like the maple syrup urine aspect of it, conversation starter.

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Fenugreek is a herb that is highly produced in Arabic regions and India. It is commonly used as a folk medicine to enhance libido and masculinity, and has a long track record of alleviating disturbances in blood sugar metabolism (diabetes). Fenugreek is also recommended as a tea to enhance milk production in new mothers, and although evidence is limited for this claim it seems to be true.

The seeds are highly versatile, and can be: eaten as seeds, brewed into a tea, made into a flour and cooked as bread, or pressed into an oil. Eating as seeds or using fenugreek flour seem to be the most effective at blood sugar control, although there are benefits to all methods.

It possesses many components, although it is most well known for the compound 4-hydroxyisoleucine. 4-hydroxyisoleucine is one of the compounds that works to normalize glucose metabolism, although the other compounds trigonelline (named after the fenugreek plant, Trigonella), galactomannin, and the trigoneosides can all work in concert to help blood sugar.

It has been shown in only one human study to enhance Testosterone, although this is currently contested.

It also has an odd effect of making body secretions smell like maple syrup, due to a metabolic known as sotolon.

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Also Known As

Trigonella foecum-graecum, fenugreek seeds


Things to Note

  • Fenugreek may enhance libido, but is otherwise non-stimulatory
  • Has been used historically as a tea, and thus many active constituents may be water soluble. Fenugreek tea does show some insulin sensitizing activity.[1]
  • Due to the sweet aromatic sotolon, consuming large doses of fenugreek may give off a sweet scent to the urine

Is a Form of


Goes Well With

  • Fish Oil (Suppressing after-meal glucose spikes)

Caution Notice

Fenugreek shows teratogenic potential when superloaded into pregnant rats, and is suspected of causing birth-defects in large doses.

It would be prudent to avoid fenugreek supplementation during pregnancy, although it would be fine to use after birth as a galactogogue (milk producing agent); which it shows efficacy as.

Examine.com Medical Disclaimer

For the purposes of increasing milk production in women, there isn't much evidence to go on for 'best' dosage; somewhere in the range of 500-1000mg would be advisable.

Animal models showing reduced Blood Glucose are in the range of 50mg/kg bodyweight, although 2-5g of the whole fenugreek have shown some benefit in human experiments on diabetes.

For sexuality in males (aphrodisia and possible testosterone boosting) 500-600mg of a Fenugreek product containing 50% Fenusides by weight (the brand name 'Testofen' has been used in studies) may be needed.


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An interesting herb, and potentially a 5-alpha reductase inhibitor (recent study added has shown declines in DHT in human subjects); the maple syrup urine phenomena is a very good conversation piece to many, but it makes me smell horrid.

Anti-diabetic apparently, but not-too-significant effects on other parameters.


Kurtis Frank

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Fenugreek has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
BTestosterone

Although there is limited evidence to support an increase in testosterone, more evidence than not denies such an increase

BAppetite

Variable effects on appetite, but it seems the fenugreek fibers (not commonly in supplements) may reduce appetite similar to most dietary fibers while the saponins (commonly... show

BInsulin

No consensus as to the influence of fenugreek on insulin levels

CFat Mass

Minor

A lone study measuring fat mass in athletes given fenugreek noted a reduction in fat mass, which was not to a remarkable degree

CDHT

Minor

A decrease in DHT has been noted following consumption of fenugreek seeds in otherwise healthy men, but appears to be unreliable

CEstrogen

No significant influences detected on estrogen levels

CLean Mass

No demonstrated benefit to lean mass accrual in otherwise healthy trained men given a workout program

CGlycogen Resynthesis

Minor

Mixed influence on glycogen resynthesis rates, but may have a possible benefit

CBlood glucose

Minor

Appears to result in a decrease of blood glucose following ingestion of fenugreek

CLibido

Notable

Increases in libido have been noted before, which is notable due to the lack of significant influence on testosterone and possible suppression of DHT (theoretically should... show

CProlactin

No detectable interactions with fenugreek and prolactin levels

CProstate Specific Antigen

No significant influence on prostate specific antigen levels

CMilk Production

Strong

Increases in milk production have been noted in lactating women given fenugreek, and appears to be a fairly significant degree of improvement with the best trial conducted... show

CInsulin Sensitivity

Minor

An increase in insulin sensitivity has been noted with fenugreek ingestion

CHDL-C

Minor

An increase in HDL-C has been associated with fenugreek ingestion

CTriglycerides

Minor

May reduce triglyceride levels

CGlycemic control

Minor

May improve glycemic control secondary to reduction in blood glucose, although this may be more indicative of fenugreek fibers than the saponin content

CCortisol

No significant influence on cortisol levels following fenugreek ingestion

CLeptin

No significant influences detected on circulating leptin levels with fenugreek


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Table of Contents:


Edit1. Source and Composition

1.1. Sources

Fenugreek seeds and extract comes from the plant Trigonella foenum-graecum L and has been used historically for various uses such as antispasmodic, appetite stimulant, high cholesterol, wounds, blood cleanser, and expectorant effects.[2][3] It is derived from both Ayurveda (mostly) and Traditional Chinese Medicine (to a lesser degree)[3] and unlike most traditional medicines it also appears to be a condiment.[3]

1.2. Composition

Fenugreek tends to contain:

  • Trigonelline[4]
  • 4-hydroxyisoleucine[5] and its precursor, 2-oxoglutarate.[6]
  • Protodioscin[7] similar to Tribulus Terrestris
  • The two Trigoneosides, Trigofaenoside A and Glycoside D[8][7]
  • Diosgenin[7][9] and Yamogenin[10][7][10]
  • GII, a compound currently unnamed[11]
  • 3-hydroxy-4,5-dimethyl-2(5H)-Furanone (HDMF), otherwise known as sotolon; the fenugreek maple syrup aromatic[12][13]
  • Trypsin and Chymotrypsin inhibitors[14]
  • Potassium at 603+/-15mg/100g[15]
  • Magnesium at 42+/-5mg/100g[15]
  • Calcium at 75+/-9mg/100g[15]
  • Zinc 2.4+/-0.2mg/100g[15]
  • Manganese and Copper both at 0.9+/-0.1mg/100g[15]
  • Iron at 25.8+/-1.2mg/100g[15]

Dietary carbohydrates and fibers (the latter of which constitutes 6.28-9.3% of total seed weight[16]) include:

  • Soluble fibers as galactomannins[17], with a galactose:mannose ratio of 1.5:1[18]

The fatty acid component of Fenugreek (4.51-7.1% of dry weight overall[15][16]) consists of mostly oleic (16.3%), linoleic (50%), and linolenic acids (24.4%).[19]

Fenugreek oil (aromatic component) contains Neryl acetate (17.32%), Camphor (16.32%), β-Pinene (15.05%), β-caryophyllene (14.63%), 2,5-dimethylpyrazine (6.14%), Geranial (4.81%), 6-methyl-5-hepten-2-one (4.48%), 3-octen-2-one (4.32%), α-selinene (4.04%), α-Terpineol (2.77%), α-Campholenal (2.63%), α-pinene (2.61%), and γ-Terpinene (2.08%).[20]

The protein content of the seeds per se appear to be 12.9-28.4%, highly variable.[15][16]

1.3. Standardizations

A standardized hydroalcoholic extract of Fenugeek to isolated the bioactive Trigonelline is known as SFSE-T.[21]


Edit2. Neurology

2.1. Mechanisms

In one in vitro study, crude fenugreek extract was found to possess acetylcholinesterase inhibitory properties.[22] The IC50 of this inhibition was 53+/-17.33mcg/mL for the ethyl acetate extract and 9.23+/-6.08mcg/mL for the alkaloids of fenugreek.[22] These anticholinergic effects do not appear to be seen in vivo following oral ingestion of an extract of Fenugreek standardized for Trigenolline.[21]

An ethanolic extract of fenugreek seeds appears to inhibit Monoamine Oxidase A (MAOA) with an IC50 of 4mcg/mL.[23]

When assessing MAO-B activity following ingestion of a Fenugreek extract high in Trigonelline, there does not appear to be any significant influence following a single ingestion.[21]

An ethanolic extract of fenugreek has failed to show affinity to the serotonin receptor, suggesting no interactions.[23]

2.2. Appetite

A study in rats using 42mg/kg of Fenugreek suggests an increase in appetite[24] which has been replicated in humans at 40mg/kg bodyweight of the aqueous extract in otherwise healthy volunteers.[25]

In obese persons, fenugreek (1176mg) taken daily appeared to reduce spontaneous fat intake without significantly affecting appetite overall[26][27] while the isolated fibers (4-8g) daily seem to induce satiety in obese persons.[28]

Has been implicated in modulating appetite, with an increasing effect in persons of normal weight (association, not known if normal weight is a mandatory prerequisite) and either satiating or no stimulating effect in obese persons.

At least one study has noted a preferential switch of appetite away from dietary fatty acids

2.3. Aphrodisia

Fenugreek may also enhance male libido when ingested at 600mg a day (Testofen brand name, 50% Fenusides) in two divided doses for 6 weeks.[29] The primary measurement was the self-reported score on the Derogatis interview for sexual functioning-self report (DISF-SR[30]) and there was a reported global improvement as well as significant improvements on the subscales of satisfaction with orgasm and sexual desire; this study was not affiliated with the producer of the supplement.[29]

2.4. Parkinson's

A single oral dose of 10-100mg/kg SFSE-T given to rats prior to 6-Hydroxydopamine toxicity (damages a similar area of the brain observed to be damaged in Parkinson's and thus is an animal model of research) and MPTP neurotoxicity noted that pretreatment of 30mg/kg was associated with less signs of neural toxicity when pretreated, but not when SFSE-T followed neurotoxicity.[21]

[21]


Edit3. Cardiovascular Health

3.1. Absorption

In the intestines, the fiber component of fenugreek seeds can suppress uptake of cholesterol and bile acids.[31]


Edit4. Interactions with Glucose Metabolism

4.1. Absorption

Fenugreek as a whole can attenuate the absorption of carbohydrates by acting as an alpha-amylase and maltase inhibitor (starch and maltose digestive enzymes, respectively).[31][32]

This has been noted in vivo with enugreek Oil (15% Fish Oil by weight) at 5% of feed in diabetic rats is associated with a 51% reduced AUC of plasma glucose following a meal associated with reduced carbohydrate enzyme activity (46% and 37% reduction for pancreatic α-amylase and maltase, respectively; 52% and 35% for plasma).[20]

The reduction of serum glucose following a meal has been noted in otherwise healthy humans.[33]

4.2. Mechanisms

It has been noted that the steroidal saponins per se do not possess significant influence on glucose metabolism[24] and that de-gumming Fenugreek (removing soluble fibers) reduces the ability of Fenugreek to attenuate post-prandial blood glucose spikes.[33]

4.3. Pancreas

A protective effect on pancreatic beta-cells has been noted with fenugreek seed ingestion in diabetic rats[20] which has been noted with the isolated steroidal saponin content.[34]

4-hydroxyisoleucine (henceforth 4OH-Ile), mostly exclusive to fenugreek (beyond some bacterial synthesis either naturally[35][36] or via modification[37]) can induce insulin secretion from pancreatic beta-cells under conditions of high glucose concentration[38] with little to no efficacy at normal serum glucose concentrations.[38] 4OH-ILE does not appear to interfere with other inducers of insulin secretion such as Leucine[38] and in doses of 50mg/kg bodyweight can reduce glucose, LDL, and insulin in diabetic mice.[39][40][41]

4.4. Interventions

In streptozotocin-induced diabetic rats, 1,500mg/kg of fenugreek seeds daily for 21 days was associated with a 58% reduction in blood glucose levels (still 116% higher than true control) with no significant influence on insulin.[42] Reduction in blood glucose have also been noted in Alloxan-induced diabetic rats (2-8g/kg of the seeds).[43]

21 days of 1,500mg/kg Fenugreek is associated with improvements in the hepatic enzymes G6P (59% of the change seen via diabetes was reversed) and G6P dehydrogenase (30%) as well as improving hepatic glycogen storage; phosphofructokinase, reduced during diabetes, was unaffected.[42] A beneficial alteration of hepatic enzymes has also been noted in Alloxan-induced diabetic rats in both the kidneys and liver (5% of the rat diet)[44]

Appears to hold some promise in reducing biochemical markers of diabetes in diabetic rats

One study using high doses of Fenugreek (2-8g daily) in alloxan induced diabetic rats noted that the healthy control rats also experienced a reduction in blood glucose.[43]

This appears to be relevant in humans with Type I diabetes (100g defatted Fenugreek)[45] as well as Type II diabetics, where a 53% increase in insulin sensitivity was noted via HOMA relative to the control group using 1g daily of a hydroalcoholic extract.[46]

Benefits for glycemic control have been seen with the seeds themselves,[47][48] defatted seed extract[49] and whole seed powder.[43][33][50][51] Fenugreek has been successfully incorporated into a bread product at 5% fenugreek flour by weight without exerting adverse taste effects onto the bread, this has been used in vivo to lower the glucose spikes after eating the bread in diabetics.[52]


Edit5. Fat Metabolism and Obesity

5.1. Interventions

One study using fenugreek at 2,500mg twice a day for 3 months noted no changes to blood sugars or blood lipids in healthy individuals, but a reduction in blood sugar in persons with Type II diabetes and a reduction in blood lipid parameters (cholesterol and triglycerides) in persons with both Coronary Artery Disease and diabetes.[53] This suggests that fenugreek has the ability to lower blood lipids, but it works vicariously though fixing problems in glucose metabolism.[53]


Edit6. Skeletal Muscle Mass and Performance

6.1. Skeletal Muscle

When administered at 900mg and in conjunction with 3.5g Creatine monohydrate, fenugreek+creatine appears to be as effective at increasing lean body mass and strength over 8 weeks as creatine alongside 70g dextrose.[54] A few problems with this latter study include no true control group (comparative study), the Fenugreek group weighting less and pressing more at baseline (possibly poor randomization), and funding from Indus Biotech.

6.2. Glycogen

A review[55] notes its pluripotent effects of the above in addition to activating muscular uptake of glucose by activating PI3K, an intermediate in insulin signalling.[56] This increase of muscular uptake may enhance glycogen replenishment after exhaustive exercise[57] but has been contested.[58] The difference may lay in benefits being seen after HIIT training (80% VO2 max intervals) compared with aerboic exercise (50% VO2 max constant).


Edit7. Fenugreek and Femininity

7.1. Lactation

Fenugreek is a commonly recommended herb for increasing milk production in pregnant women,[59] and is seen by some as one of the few herbs with promising evidence.[60][61] It is told (traditionally) that fenugreek 'stimulates sweat production' and that this influences milk production as the two structures (sweat glands and milk glands) are similar.[62][63]

A few trials have been conducted on the matter, and fenugreek seems to be able to enhance milk production in recent mothers more than placebo.[62] In which control and placebo had 31.1+/-12.9mL and 38.8+/-16.3mL respectively, the fenugreek group was able to produce 73.2+/-53.5mL after consuming at least 3 cups (200mL) of fenugreek tea (Still tea, Humana) for three days.

The mechanism of action is not specifically known, but may be related to phytoesteogens or diosgenin.[62] Not many studies have detected the presence of Fenugreek bioactives in breast milk, but one assessing the anti-oxidant capacity of breast milk from mothers drinking Fenugreek tea failed to find a significant difference relative to placebo.[64]

Limited evidence to support Fenugeek enhancing milk production, but Fenugreek Tea does have preliminary evidence in support of this traditional usage.

7.2. Pregnancy

Fenugreek, at dosages of 800mg/kg bodyweight or above in rats (128mg/kg human estimated dose), is potentially a teratogenic substance[65] that may cause birth defects when consumed by a pregnant woman; the mechanism of teratogenesis is hypothesized to be through inhibiting stem cell differentation.[66]

7.3. Breast Enhancement

Fenugreek is sometimes used as a breast enhancing substance;[67] there is no evidence to support this notion.

7.4. Menopause

Fenugreek has traditionally (and currently via non-medical associations) been recommended as a treatment for menopause with regard to lessening vaginal dryness;[68] there is currently insufficient evidence to support these claims.


Edit8. Interactions with Hormones

8.1. Testosterone

In rats, oral intake of 10-35mg/kg Fenugreek furostanols for 4 weeks has caused an increase in the weight of the levator ani muscle (thought to be indicative of anabolic actions in males) with no significant influence on circulating testosterone levels.[69] Prostate weight was not altered in this study.

Possible androgenic effects independent of testosterone, although no evidence exists to support the notion that this is at all a powerful androgenic effect (if it is replicated)

Fenugreek has once been shown at 500mg (brand name Testofen) to increase serum testosterone over a period of 8 weeks in resistance trained males relative to placebo (experiencing a decline in testosterone relative to baseline)[70] although another study (which noted a decrease in DHT, a testosterone metabolite) failed to find any significance influence on total or free testosterone using similar methodology[71] and a study using 600mg of Testofen for a period of 6 weeks in otherwise healthy man has similarly failed to find an increase in testosterone.[29]

In regards to DHT, the one study to measure DHT noted a 9.42% decrease relative to baseline over 8 weeks supplementation of 500mg Fenugreek.[71]

Mixed results on an increase in testosterone in otherwise healthy men, although there appears to be support for the 5alpha-reductase properties of Fenugreek via the reduction in DHT

8.2. Thyroid Hormones

In rats given exogenous thyroid hormones (T4 and T3) in order to induce high blood sugar, 220mg/kg of the seeds of Fenugreek was able to suppress the rise in blood glucose and the rise of thyroid hormones; the potency of which being comparable to 500mg/kg Allium sativum and 10mg/kg propyl thiouracil (known anti-thyroid as active control).[72]


Edit9. Interactions with the Liver

9.1. Hepatoprotection

Fenugreek has been noted to protect against oxidative liver pathology at 5% of male rat feed against Aluminum Chloride toxicity.[73]

9.2. Ethanol

Fenugreek appears to be recommended for Alcohol-related complications according to its traditional usage, similar to such herbs as Pueraria Lobata and Hovenia dulcis.[74]

An in vitro study using Chang liver cells (non-malignant cell model for studying EtOH toxicity[75]) incubated with 30mM alcohol, the reduction of cell viability to 45% was attenuated in a concentration dependent manner to 48% (20mcg/mL), 52% (40mcg/mL), and 75% (60mcg/mL) with simultaneous incubation; the active control of Silymarin (from Milk Thistle) at 30mcg/mL preserved 79% of cells.[76] Silymarin and the highest dose of Fenugreek polyphenols were similarly effective in preserving lipid peroxidation, LDH leakage, and mitochondrial permeability.[76]

A water extract of Fenugreek seeds concurrently during 60 days of alcohol ingestion was associated with a reduction in the rise of oxidation and liver enzymes noted in the serum of rats given ethanol alone, suggesting protective effects.[77]

May protect liver cells in response to ethanol ingestion (coadministration), although there is not a large amount of evidence for this claim. One study, comparing Fenugreek to Silymarin, suggest the potency is not remarkable either


Edit10. Interactions with Organ Systems

10.1. Eyes

An alcoholic extract of fenugreek seeds at 2,000mg/kg daily in alloxan-induced diabetic rats was able to reduce diabetes-induced cataract formation, although to a lesser protective effect when compared to Pterocarpus marsupium bark at 1,000mg/kg.[78]

10.2. Testes

At least one study in diabetic rats has noted that ingestion of Fenugreek saponins was associated with preservation of steroidal synthesis enzymes in the testes of rats (HMG-CoA redutase, 3β-HSD, Malic enzyme and G6P-DH)[34] which are reduced during diabetes.

Intakes of up to 35mg/kg of the furostanol component are not associated with any adverse effects to the testes (or prostate) as assessed by histology or organ weight.[69]


Edit11. Nutrient-Nutrient Interactions

11.1. Fish Oil

Fish Oil appears to increase the efficacy of fenugreek in reducing post-prandial blood sugar spikes, as a mixture (5%) of half fish oil and half fenugreek showed a greater attenuation of blood sugar than the same amount (5%) of fenugreek alone.[20]

11.2. Arcabose and Drug Delivery

Arcabose is an alpha-glucosidase inhibitor that is used for treatment of diabetes by attentuating the release of glucose into the blood. In 1:0.8-1.2 weight ratios of Arcabose:Fenugreek Gum (the soluble fiber aspect), fenugreek is able to increase the release of arcabose from being fully absorbed in one hour and delay complete absorption for up to 8 hours, suggesting that fenugreek gum can enhance intestinal half-life.[18]

Due to fenugreek's own ability to be anti-diabetic, it works in synergism on drug delivery and additive on attentuating glucose spikes.[18]


Edit12. Safety and Toxicity

12.1. General

An oral dose of 3g/kg bodyweight of ethanol-extract fenugreek failed to show adverse effects in one study, and higher doses were not studied as this was above the most hypoglycemic dosage of 1g/kg.[79] In another study, the LD50 was established at 3.5g/kg in female mice and 4.1g/kg in males.[66]

Allergies to fenugreek have been noted, and seem to be tied in with the entire Leguminoseae family, and both subjects noted responsiveness to chickpeas as well; if one is allergic to chick peas, they may react to fenugreek.[80]

12.2. Pregnacy/Motherhood

Fenugreek has been historically used as an abortifacient, or a compound capable of inducing abortions.[81] The proposed mechanisms are through contractions of the uterine wall, which would also induce birth in the late third trimester.

When overfed to rats (800mg/kg bodyweight), fenugreek also has shown teratogenic potential by possibly interfering with stem cell division.[65]. This dose roughly translates to 128mg/kg in humans.

12.3. False Diagnosis of Maple Syrup Urine Disease

Maple Syrup Urine Disease (MSUD) is a condition that results from improper metabolism of branched-chain amino acids. The aromatic in fenugreek, sotolon, may be used as a diagnostic criteria for MSUD as it exists in the urine of those persons with this metabolic defect and gives the characteristic sweet-scent.[13] It normally does not appear in healthy person's urine due to no dietary intake, but may appear in those who drink or consume fenugreek, leading to a false diagnosis.[82] Maternal consumption of sotolon can also transfer into the baby after birth, and cause trans-generational false diagnosis.[83]

A few human interventions note a side-effect of 'peculiar' or 'sweet' smell in the urine.[27]

References

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