Nettle Root and SHBG

[allen_australia]

As I understand it, Nettle Root binds to SHBG, thus reducing the amount of estradiol/estrogen that can bind to it and cause hair loss.

However, from the Life Extension site regarding Hormone Modulation Therapy, this means it also prevents testosterone from binding to it, thus increasing free testosterone :

"A highly concentrated extract from the nettle root provides a unique mechanism for increasing levels of free testosterone. European research has identified constituents of nettle root that bind to SHBG in place of testosterone, thus reducing SHBG's binding of free testosterone. As the authors of one study stated, these constituents of nettle root may influence the blood level of free, i.e., active, steroid hormones by displacing them from the SHBG binding site."

Wouldn't this be bad for hair? Or is the deal with someone like IH's protocol, that nettle binds to the SHBG, freeing up testosterone, then you take other things like Green Tea/Grape Seed etc to prevent the aromatase of that free testosterone to DHT?

 

[allen_australia]

?????

 

[DHTHater]

No idea why this hasn't been addressed beyond the obvious first assumption there's an unfortunate shortage of molecular biologists, pharmacologists, botanists, and endocrinologists on the board, but this is something I'd be curious to learn about myself.

Perhaps if the question were repeated in another forum (endocrinology, pharmacology, pharmacogenetics etc).

Because of the claims behind Stinging Nettle as a potentially potent inhibitor of the conversion of testosterone to dihydrotestosterone, this plant really should be discussed more than it has been thus far IMO.

 

[vauxall]

I am thinking of starting Nettle root supplementation but not necessarily for hair loss but because I want to boost my testosterone levels. Here's a couple of studies and let's see if there are any comments:

Z Naturforsch C. 1997 Nov-Dec;52(11-12):834-43.
Interaction of lignans with human sex hormone binding globulin (SHBG).
Schöttner M, Gansser D, Spiteller G.
Lehrstuhl Organische Chemie I, Universität Bayreuth, Germany.

Abstract
Lignans bind to sex hormone-binding globulin (SHBG). The lignan with the highest binding affinity is (+/-)-3,4-divanillyltetrahydrofuran. In a double Stobbe condensation--without use of protecting groups--a wide variety of lignans with different substitution pattern in the aromatic and aliphatic part of the molecule was synthesized. These lignans were tested in a SHBG-binding assay which allowed to deduce the following relationship between structure and activity: 1) (+/-)-diastereoisomers are more active than meso compounds 2.) the 4-hydroxy-3-methoxy (guajacyl) substitution pattern in the aromatic part is most effective 3.) the activity increases with the decline in polarity of the aliphatic part of the molecule.
PMID: 9463941 [PubMed - indexed for MEDLINE]

J Nat Prod. 1998 Jan;61(1):119-21.
Lignans interfering with 5 alpha-dihydrotestosterone binding to human sex hormone-binding globulin.
Schöttner M, Spiteller G, Gansser D.
Lehrstuhl für organische Chemie, Universität Bayreuth, Germany.

Abstract
The natural lignans (-)-3,4-divanillyltetrahydrofuran (1), (-)-matairesinol (2), (-)-secoisolariciresinol (3), (+/-)-enterolactone (4), (+/-)-enterodiol (5), and nordihydroguaiaretic acid (NDGA) (6) reduce the binding of 3H-labeled 5 alpha-dihydrotestosterone (DHT) to human sex hormone-binding globulin (SHBG). (-)-3,4-Divanillyltetrahydrofuran (1) has the highest binding affinity (Ka = 3.2 +/- 1.7 x 10(6)M-1) of all lignans investigated so far; the reversibility of its binding and a double reciprocal plot suggest a competitive inhibition of the SHBG-DHT interaction. Increasing hydrophobity in the aliphatic part of the lignans (butane-1,4-diol-butanolide-tetrahydrofuran structures) leads to higher binding affinity. In the aromatic part, a 3-methoxy-4-hydroxy substitution pattern is most effective for binding to SHBG.
PMID: 9461660 [PubMed - indexed for MEDLINE]

Planta Med. 1997 Dec;63(6):529-32.
Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).
Schöttner M, Gansser D, Spiteller G.
Lehrstuhl Organische Chemie I, Universität Bayreuth, Germany.

Abstract
Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).
PMID: 9434605 [PubMed - indexed for MEDLINE]

 

[vauxall]

Two more:

Phytomedicine. 2007 Aug;14(7-8):568-79. Epub 2007 May 16.

A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix.
Chrubasik JE, Roufogalis BD, Wagner H, Chrubasik S.

Department of Forensic Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg, Germany.

Abstract
Nettle root is recommended for complaints associated with benign prostatic hyperplasia (BPH). We therefore conducted a comprehensive review of the literature to summarise the pharmacological and clinical effects of this plant material. Only a few components of the active principle have been identified and the mechanism of action is still unclear. It seems likely that sex hormone binding globulin (SHBG), aromatase, epidermal growth factor and prostate steroid membrane receptors are involved in the anti-prostatic effect, but less likely that 5alpha-reductase or androgen receptors are involved. Extract and a polysaccharide fraction were shown to exert anti-inflammatory activity. A proprietary methanolic nettle root extract and particular fractions inhibited cell proliferation. Isolated lectins (UDA) were shown to be promising immunomodulatory agents, having also anti-viral and fungistatic effects. However, despite these in vitro studies it is unclear whether the in-vitro or animal data are a surrogate for clinical effects. The clinical evidence of effectiveness for nettle root in the treatment of BPH is based on many open studies. A small number of randomised controlled studies indicate that a proprietary methanolic extract is effective in improving BPH complaints. However, the significance and magnitude of the effect remains to be established in further confirmatory studies before nettle root treatment may be accepted in the guidelines for BPH treatment. The risk for adverse events during nettle root treatment is very low, as is its toxicity. Pre-clinical safety data remain to be completed.

PMID: 17509841 [PubMed - indexed for MEDLINE]

Planta Med. 1995 Apr;61(2):138-40.

Aromatase inhibitors from Urtica dioica roots.
Gansser D, Spiteller G.

Lehrstuhl Organische Chemie I, Universität Bayreuth, Norwood I, Universitätsstrasse 30, D-95440 Bayreuth, Germany.

Abstract
Methanolic extracts of stinging nettle (Urtica dioica L.) roots were investigated for aromatase inhibition. Enzyme inhibition was detected only after appropriate chromatographic separation. Inhibitory effects on aromatase could be demonstrated in vitro for a variety of compounds belonging to different classes. The following compounds developed weak to moderate activity: secoisolariciresinol, oleanolic and ursolic acid, (9Z,11E)-13-hydroxy-9,11-octadecadienoic acid, and 14-octacosanol (5). Inhibitory effects on aromatase have been known to date neither for pentacyclic triterpenes nor for secondary fatty alcohols. The potential physiological significance of the above findings is discussed. Compound 5 is a previously unknown constituent of plants.

PMID: 17238068 [PubMed]

 

[Hoppi]

Ah well this is along the misterE lines of thinking isn't it?

Because I always thought that SHBG's purpose was simply to mop up sex hormones. I thought they bound to SHBG, and were then released from the body. So, increased SHBG means less T and E in the body.

However, individuals like misterE claim that, once bound, these sex hormones (particularly estrogen) continue to exert negative effects, most notably on our hair. I do wish I knew the answer, and now that more people are coming forward with this I am increasingly more curious to investigate this further.

In any case, SDG or 7-HMR lignans will prevent estrogen from binding, and DIM, grape seed extract and resveratrol will reduce estradiol I believe by inhibiting the aromatase pathway.

I am unsure about how nettle root fits in, but I too am very curious

 

[Bryan]

As I understand it, Nettle Root binds to SHBG, thus reducing the amount of estradiol/estrogen that can bind to it and cause hair loss.

I think that's a poorly written sentence. Are you saying that the binding of estrogen to SHBG causes hair loss, or are you saying something else? :dunno:

However, from the Life Extension site regarding Hormone Modulation Therapy, this means it also prevents testosterone from binding to it, thus increasing free testosterone :

"A highly concentrated extract from the nettle root provides a unique mechanism for increasing levels of free testosterone. European research has identified constituents of nettle root that bind to SHBG in place of testosterone, thus reducing SHBG's binding of free testosterone. As the authors of one study stated, these constituents of nettle root may influence the blood level of free, i.e., active, steroid hormones by displacing them from the SHBG binding site."

Wouldn't this be bad for hair? Or is the deal with someone like IH's protocol, that nettle binds to the SHBG, freeing up testosterone, then you take other things like Green Tea/Grape Seed etc to prevent the aromatase of that free testosterone to DHT?

Testosterone isn't "aromatased" into DHT. Aromatase is an enzyme that converts testosterone into estrogen. You're thinking of 5a-reductase.

 

[Bryan]

Because of the claims behind Stinging Nettle as a potentially potent inhibitor of the conversion of testosterone to dihydrotestosterone, this plant really should be discussed more than it has been thus far IMO.

Where did you hear that stinging nettle is a potentially "potent inhibitor" of 5a-reductase?

 

[Bryan]

I am thinking of starting Nettle root supplementation but not necessarily for hair loss but because I want to boost my testosterone levels. Here's a couple of studies and let's see if there are any comments: {snip studies}

I've always been dubious about the assumption people seem to make that altering levels of SHBG in some way would necessarily have the expected effect on testosterone levels. The brain keeps close watch over levels of androgenic stimulation in the body; I strongly suspect that if you found some way to decrease the action of SHBG (by using some plant that binds with it, for example), your body would simply compensate by making less testosterone.

 

[Bryan]

Ah well this is along the misterE lines of thinking isn't it?

Because I always thought that SHBG's purpose was simply to mop up sex hormones. I thought they bound to SHBG, and were then released from the body. So, increased SHBG means less T and E in the body.

Think very carefully about the following question: what do you suppose would happen if we could somehow go in and magically remove molecules of testosterone from your body, like if we could somehow wave a magic wand and they would simply disappear in a POOF of logic?

I'll tell you what would happen: your body would soon notice that those molecules of testosterone were gone, and would start making more of them, to compensate for the loss. Understand what I'm saying to you? :smack:

However, individuals like misterE claim that, once bound, these sex hormones (particularly estrogen) continue to exert negative effects, most notably on our hair.

Estrogen doesn't exert negative effects on hair. Estrogen is beneficial for scalp hair, as numerous studies have shown.