Progesterone Supplementation Caused Spider And Vericose Veins. Why?

Nikki

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Jul 28, 2016
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118
"keeping the estrogen and serotonin low, with higher thyroid,
pregnenolone, and progesterone can restore smooth muscle tone to the veins." RP

Each time I have tried progesterone supplementation (topical bioidentical cream, and oro-topical Progest E) I have gotten spider veins. I never had them before using Progesterone. My mother got vericose veins during pregnancy, so I may be predisposed to developing them under certain hormonal conditions. Stopping progesterone supplementatoin halted the develeopment of spider veins but did not cause existing ones to improve. Does anyone have a logical explanation for this. Do you think it's a thyroid issue? I do have a lot of hypothyroid symptoms yet all of my thyroid levels were perfect per my ND (see link if image doesn't display). I am about to go throug IVF and don't want to risk this happening on a large scale from the hormones. I am sure it is not healthy. The one spider vein I developed about 6 years ago has been uncomfortable if I wear anything tight in that area. When I began experimenting with Progest E, the vein started hurting without anything contacting it. This was my wake up call. After I realized I was having issues with my veins again, I noticed how many spider veins had developed. This can't be healthy.

Does anyone have experience with this event and know how to explain/avoid it? I can simply not use progesterone, but I think I need it to sustain pregnancy.

Thanks for any help you folks can offer.


 

Nikki

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Thread starter
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Jul 28, 2016
Messages
118
"keeping the estrogen and serotonin low, with higher thyroid,
pregnenolone, and progesterone can restore smooth muscle tone to the veins." RP

Each time I have tried progesterone supplementation (most recently Progest E) I have gotten spider veins. I never had them before using Progesterone. My mother got varicose veins during pregnancy, so I may be predisposed to developing them under certain hormonal conditions. Stopping progesterone supplementation halted the development of spider veins but did not cause existing ones to improve.

Does anyone have a logical explanation for this. Do you think it's a thyroid issue? I do have a lot of hypothyroid symptoms yet all of my thyroid levels were perfect without supplementation per my ND (see link if image doesn't display).

I am about to go through IVF. Before I do that I want to be sure I educate myself on hormones and understand what they might do to my body. I am certain spider veins are evidence of poor vein health. I don't feel like my ND is an expert on this specific matter based on a yelp review from one of his patients. She developed varicose veins and generalized cellulite after he prescribed her progesterone. She alleges that the ND said it was impossible that the progesterone caused the effects but another doctor confirmed the possibility. Given my tendency to get the spider veins, I don't feel confident with the doctor I had been going to and am seeking another. I also do not trust the reproductive endocrinologists who will just want to take my money and have no regard for my long term health.

I trust my new friends here on this board to steer me in the correct direction. Does anyone have experience with this event and know how to explain/avoid it? Of course, I could simply abstain from using progesterone, but it is necessary to sustain pregnancy. I feel certain that, if I didn't supplement, I would miscarry.

Thanks in advance for any help you folks can offer.
Dropbox - Screenshot 2016-12-25 18.54.54.jpg

 

Stryker

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Oct 24, 2013
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"The presence of PR in the media of saphenous veins suggests that progesterone may influence venous structure and/or function. Physiological venous changes have been described on the basis of hormonal status, such as venous stasis during luteal phase or pregnancy. Consequently, venous blood flow may be directly modulated by steroid hormones. Changes in uterine blood flow, known to occur in the cycling uterus or during pregnancy,41 were previously shown to be directly modulated by steroid hormones via their specific receptors (ER and PR) present in vascular smooth muscle cells.6 7 In particular, the presence of PR staining in smooth muscle cells of spiral arteries in early pregnancy7correlates with large increases in endometrial and myometrial blood flow that occur to support fetal growth and homeostasis. The role of progesterone in the saphenous vein remains to be determined. We have reported preliminary data on the in vitro progesterone-induced decrease of noradrenaline and calcium-induced contractions from isolated human saphenous veins.42 Whether or not progesterone has also an effect on the structure of the vein via a regulation of cell proliferation remains unknown."



Is it possible that high adrenaline is masking your possibly damaged leg veins and when you administer progesterone is it reduced and the varicose veins become prominent?

"Its actions are to increase peripheral resistance via α1 receptor-dependent vasoconstriction"
 

tara

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Mar 29, 2014
Messages
10,273
I have developed some spider veins on my legs over the last three years. Don't know which of the many factors might be responsible. I have been supplementing progesterone. I also gained some weight (and then lost some). My guess was that the spider veins were related to the weight gain. I'm older than you - early fifties.
 

Stilgar

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May 16, 2013
Messages
292
I went through a time of using a lot of progesterone and whilst it helped me in many ways, I often overdid it hoping it was a miracle cure. I asked Ray about it, because my teeth were moving which freaked me out when I used a lot of progesterone and he said that high progesterone and low androgens and background inflammation can be responsible.

How is your protein intake, gut health etc?
 

charmer

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Joined
Oct 25, 2014
Messages
60
I have one visible varicose vein and some spider veins too. I mix luteina progesterone pill in DMSO and apply it topically all over my legs (30-50mg at a time), my vein buldge disappears. My skin redness goes away, my pores diminish and skin gets much smoother. I think some other hormones should be interfering with progesterone conversion, but I don't know exactly.

A few years ago I was experimenting with utrogestan internally (progesterone in peanut oil) and first it made me euphoric, in the next few days I felt very hysterical and my skin aged a lot just in a few days. Peat said my intestinal bacteria might have converted it into estrogen. This could be an explanation for an oral root.

As for topical, any chance you didn't keep it consistent? I'm thinking it would be harmful to have deviations, when you add progesterone, then it falls and estrogen is dominating again. Maybe keeping it consistent and having a dose high enough and stable in the blood would have a different effect on you?
 
Joined
Oct 5, 2016
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Age
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Well i donno

But for me its related to estrogen

I have big varicose in my left calf

When i have high serotonin
And bloating and indegestion

It appears

So for me
Aspirine worked like charm
For varicose

But
It caused me a very bad ulcer and bleeding in my stomach for 1 month

Are you having diarrhea?
Pain and fatigue in feet ,back and hands every now and then ?
 

Koveras

Member
Joined
Dec 17, 2015
Messages
719
"Each time I have tried progesterone supplementation (topical bioidentical cream, and oro-topical Progest E) I have gotten spider veins.

"We have reported preliminary data on the in vitro progesterone-induced decrease of noradrenaline and calcium-induced contractions from isolated human saphenous veins.

I have developed some spider veins on my legs over the last three years. Don't know which of the many factors might be responsible. I have been supplementing progesterone. I also gained some weight (and then lost some). My guess was that the spider veins were related to the weight gain. I'm older than you - early fifties.

I think the mechanism Stryker posted may be relevant for some individuals - you may be interested in the citrus flavonoids Diosmin and Hesperidin, which help to maintain venous tone.

Clinically there is a preparation of those flavonoids called Daflon but supplements of micronized Diosmin/Hesperidin are available as well.

Angiology. 1994 Jun;45(6 Pt 2):531-6.
Advantage of a micronized flavonoidic fraction (Daflon 500 mg) in comparison with a nonmicronized diosmin.
Amato C1.

A randomized, double-blind, multicenter trial was performed to study the pharmacodynamic and clinical activities of Daflon 500 mg,* in comparison with a nonmicronized diosmin. Daflon 500 mg is a micronized purified flavonoidic fraction consisting of 450 mg of diosmin and 50 mg of hesperidin per tablet, which has been micronized in order to ensure a better gastrointestinal absorption. Ninety patients with chronic venous insufficiency of the lower limbs, stabilized for one year, entered the study. They received either two tablets of Daflon 500 mg or an equivalent dose of nonmicronized diosmin in two divided doses each day during two months. The following parameters were studied: functional clinical symptoms in the lower extremities, ankle circumference measurement, strain gauge plethysmographic parameters with 20, 40, and 60 mmHg venous occlusion, and clinical and biochemical acceptability. Statistically significant changes were obtained in both groups of patients in comparison with baseline values. However, the improvements in all clinical symptoms and plethysmographic parameters (maximum increase of venous volume at 60 mmHg and total time for emptying) were significantly better with Daflon 500 mg than with nonmicronized diosmin. The clinical and laboratory acceptability was similar in both groups. However, the percentage of satisfied patients was 95% in the Daflon 500 mg group, versus 80% in the nonmicronized diosmin group (p < 0.01). In conclusion, the pharmacodynamic and clinical activities of Daflon 500 mg are superior to those of an equivalent dose of nonmicronized diosmin and demonstrate the therapeutic advantage of a micronized formulation in the treatment of chronic venous insufficiency.

Curr Vasc Pharmacol. 2015;13(6):801-8.
Effect of Micronized Purified Flavonoid Fraction Therapy on Endothelin-1 and TNF-α Levels in Relation to Antioxidant Enzyme Balance in the Peripheral Blood of Women with Varicose Veins.
Pietrzycka A1, Kózka M, Urbanek T, Stpniewski M, Kucharzewski M.

OBJECTIVE:
The aetiology of varicose veins involves various factors and pathomechanisms including endothelial cell activation or dysfunction, venous hypertension, vein wall hypoxia, shear stress disturbances, inflammatory reaction activation or free radical production. To improve our understanding of the mechanisms of potential pharmacological interventions for chronic venous disease, we evaluated the influence of micronized purified flavonoid fraction (MPFF) on the relationship between antioxidant enzyme balance, endothelin-1 (ET-1) and tumour necrosis factor-α (TNF-α) levels.
MATERIAL AND METHODS:
Blood samples were obtained from 89 women with primary varicose veins; 34 were treated with MPFF and 55 did not receive any phlebotropic drug treatment. For the evaluation of the blood antioxidant enzyme balance, catalase (CAT) and superoxide dismutase (SOD) activity was assessed and the CAT/SOD ratio was calculated.
RESULTS:
Patients taking MPFF had significantly lower ET-1 levels than those not taking MPFF [median (25-75th quartile): 24.2 (22.30-27.87) vs 37.62 (24.9-44.58) pg.ml-1; p <0.05]. In those taking MPFF, a higher CAT/SOD ratio [39.8 (24.7-72.6) vs 28.8 (16.3-57.7); p<0.05] and a lower TNF-α concentration [6.82 (4.42-13.39) vs 12.94 (6.01-27.33) pg.ml<sup>-1</sup>; p<0.05] was also observed. In women not taking MPFF, ET-1 levels increased with the CAT/SOD ratio. In those taking MPFF, the ET-1 level was stable at approximately 25.0 pg.ml<sup>-1</sup>¬ up to a CAT/SOD ratio of 100. TNF-α level increased continuously with an increasing CAT/SOD ratio; however, the highest levels of TNF-α were observed in women not taking MPFF.
CONCLUSION:
We demonstrate the ability of MPFF to effectively lower the levels of ET-1 and TNF-α in patients with chronic venous disease. Further investigations are needed to define the therapeutic potential of MPFF including the potential effect on chronic subclinical inflammation, antioxidant imbalance and vascular dysfunction during the development of chronic venous disease.

Angiol Sosud Khir. 2007;13(2):47-55.
Surgical correction of varicose vein disease under micronized diosmin protection (results of the Russian multicenter controlled trial DEFANS).
[Article in English, Russian]
Pokrovsky AV1, Saveljev VS, Kirienko AI, Bogachev VY, Zolotukhin IA, Sapelkin SV, Shvalb PG, Zhukov BN, Vozlubleny SI, Sabelnikov VV, Voskanian YE, Katelnitsky II, Burleva EP, Tolstikhin VY.

The paper presents the results of DEFANS trial (Detralex - assessment of efficacy and safety for combined phlebectomy). The study enrolled 245 patients with varicose vein disease, who underwent unilateral combined phlebectomy. The main group (n=200) received micronized diosmin (Detralex, 1000 mg/day) for 2 weeks before and 30 days after the procedure; control group (n=45) did not receive Detralex in pre- and postoperative period. Pain severity by 10-point visual analog scale (VAS), an area of subcutaneous hemorrhage in the zone of femoral great saphenous vein resection (by original 12-point scale) and subjective feelings of limb heaviness and fatigability were evaluated 7, 14 and 30 days after the procedure. Subjective symptoms and the area of subcutaneous hemorrhage were significantly lower in the main group, then in control: 7 days after the procedure VAS score was 2.9 and 3.5, respectively; hemorrhage area - 3.4 and 4.6 points, respectively. The same trend was observed for limb heaviness and fatigability, evidencing the better exercise and orthostatic tolerance among patients of the main group in early postoperative period. Quality of life assessment by CIVIQ failed to reveal statistically significant difference between main and control groups in 4-weeks postoperative follow-up. Micronized diosmin in pre- and postoperative period after plebectomy helps to attenuate pain syndrome, to decrease postoperative haematomas and accelerate their resorption, to increase exercise tolerance in early postoperative period.

Angiology. 2003 Jul-Aug;54 Suppl 1:S33-44.
From symptoms to leg edema: efficacy of Daflon 500 mg.
Nicolaides AN1.
This article reviews the mechanisms by which micronized purified flavonoid fraction (MPFF; Daflon 500 mg) acts on symptoms as well as on edema in patients with chronic venous disease, in the light of new advances in the understanding of the pathophysiology of this chronic condition. Deterioration of venous wall tone followed by valve dysfunction leading eventually to varicose veins are the key pathophysiologic features that produce venous hypertension. Both mechanical and biological factors are responsible for the deterioration of the venous wall in large veins. These are decreased shear stress and hypoxia of the media and of the endothelium, which act as triggering factors for biochemical reactions leading to inflammation. There is a body of evidence that inflammation in chronic venous insufficiency (CVI) plays a role right from the early stages of venous dysfunction and venous valve restructuring. The whole process of venous wall stretching and dilation is painful and may present as leg heaviness, a sensation of swelling, and paresthesia. Daflon 500 mg relieves symptoms, edema, and red blood cell aggregation, which cause paresthesia and restless legs. At the level of the microcirculation, dysfunction of microvessels is observed, characterized by an increase in capillary permeability followed by skin changes. The earliest manifestation of microcirculatory disorder is edema. At this level, Daflon 500 mg acts favorably on microcirculatory complications by normalizing the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and inhibits leukocyte activation, trapping, and migration. Its efficacy in decreasing CVI edema and ankle swelling has been proven in rigorous studies that are reviewed in this paper. Daflon 500 mg, a well-established oral flavonoid that consists of 90% micronized diosmin and 10% flavonoids expressed as hesperidin, may be prescribed from the very beginning of the disease for the relief of pain and edema, and in any CVI patient presenting with symptoms as well. Daflon 500 mg is thus the first-line treatment for edema and symptoms of CVI at any stage of the disease. At advanced disease stages, Daflon 500 mg may be used in conjunction with sclerotherapy, surgery, and/or compression therapy or as an alternative treatment when other treatments are not indicated or not feasible.

Angiology. 2001 Aug;52 Suppl 1:S49-56.
Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency.
Ramelet AA1.

Chronic venous insufficiency (CVI) affects a large number of people in Western countries, and is responsible for considerable inconvenience, discomfort, suffering, and costs. Micronized purified flavonoid fraction (MPFF, 450 mg diosmin plus 50 mg hesperidin-Daflon 500 mg) is a potent venotropic drug used in the treatment of venous insufficiency. Pharmacological and clinical studies demonstrated the comprehensive mode of action of Daflon 500 mg: it increases venous tone, it improves lymph drainage, and it protects the microcirculation. Clinical international, prospective, multicenter, randomized, controlled studies versus placebo studies documenting the effects of Daflon 500 mg in CVI at advanced stages with edema, skin changes, and venous leg ulcer are reviewed. In edema, one of the most frequent complaints of patients, Daflon 500 mg brings about a significant reduction in leg circumference, thanks to its capacity to inhibit inflammatory reactions and to decrease capillary hyperpermeability. The rationale for the use of Daflon 500 mg for treatment of skin disorders and venous leg ulcer is its action on the microcirculation-damaging processes. Regarding skin changes, Daflon 500 mg has been shown to improve venous trophic disorders, like gravitational (stasis) dermatitis, and dermatofibrosclerosis. In venous leg ulcer, Daflon 500 mg's clinical efficacy has been demonstrated in addition to standard treatment or versus standard treatment alone. Daflon 500 mg, thanks to its comprehensive mode of action on the veins, lymphatics, and microcirculation, is the method of choice not only in the early stages of CVI treatment, but also in the severe stages of this condition, in combination with compression treatment, sclerotherapy, and surgery if appropriate.

Angiology. 2001 Aug;52 Suppl 1:S43-7.
Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500 mg.
Bergan JJ1, Schmid-Schönbein GW, Takase S.

Early manifestations of chronic venous insufficiency (CVI) are edema, hyperpigmentation, and lipodermatosclerosis. Late complications are cutaneous ulceration and delayed healing. The specific hallmarks of this inflammation include CD68-positive infiltration into the dermal tissue, monocytes, and lymphocytes and enhanced endothelial permeability. This may lead to "fibrin cuff" formation. In addition, membrane adhesion molecules are present and cytokine expression is seen. In one experimental model of mesenteric venous hypertension, the inflammatory process was detected in its earliest stages. This was evident in the form of neutrophilic leukocyte adhesion to venular endothelium as well as migration of cells across the endothelium and basement membrane into the interstitial space. Simultaneously, parenchymal cell death was detected. This suggests that the mechanism that triggers the inflammatory reaction is venous hypertension. This may cause venous distension and a shift in fluid shear stress. Our observations suggest that patients with venous insufficiency demonstrate circulatory humoral stimulators for leukocyte activation. Otherwise, there is evidence that the inflammatory reaction is limited to the region of the venous ulceration or at least to the skin areas with severe microangiopathy. It may be that activated leukocytes traverse perivascular cuffs and release active transforming growth factor-beta1 (TGF-beta1) which has been found to be elevated exclusively in areas of clinically active CVI. Surgical intervention markedly decreases the number of dysfunctional vein segments and allows pharmacologic agents to protect normal structures from continuing damage. Daflon 500 mg, the purified micronized flavonoid fraction containing 90% diosmin and 10% hesperidin, acts favorably in venous ulcer treatment by inhibiting the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and may act favorably to inhibit leukocyte activation, trapping, and migration. Clinically, edema is reduced, ulcer healing is accelerated, and leukocyte trapping diminished. The action of micronized purified flavonoid fraction is beginning to be better understood, and as further knowledge is gained, better pharmacologic control of CVI is a tantalizing promise.

Angiology. 1997 May;48(5):391-9.
Effects of oral administration of purified micronized flavonoid fraction on increased microvascular permeability induced by various agents and on ischemia/reperfusion in the hamster cheek pouch.
Bouskela E1, Donyo KA.

The effects of a clinically used purified micronized flavonoid fraction (S 5682) containing 90% diosmin and 10% hesperidin on increased microvascular permeability induced by histamine, bradykinin, and leukotriene B4 (LTB4) were investigated by intravital microscopy in the hamster cheek pouch preparation. The authors also investigated the effects of S 5682 on macromolecular permeability increase and leukocyte adhesion during ischemia-reperfusion by using the same preparation. S 5682, suspended in 10% lactose solution, or vehicle (10% lactose) was administered orally to male hamsters for ten days at 20 mg/kg/day (10 mg/kg twice a day). Fluorescein isothiocyanate (FITC)-labeled dextran (mol wt 150,000) was given intravenously, thirty minutes after completion of the cheek pouch preparation. The leukocytes were stained by continuous IV infusion of acridine orange (0.5 mg/kg/minute). Histamine (2 microM), bradykinin (1 microM), and LTB4 (0.01 microM), applied topically for five minutes, increased the number of fluorescent vascular leakage sites in postcapillary venules. A temporary ischemia with total circulatory arrest of the cheek pouch was obtained by clamping the neck of the everted pouch. The maximum number of leaky sites (per cm2 in the prepared area) that occurred either at five minutes after the beginning of each topical application or ten minutes after the onset of reperfusion was quantified in ultraviolet light microscopy. The results from 60 animals divided into 10 groups of 6 animals each are presented as means +/- SEM. In comparison with vehicle, S 5682 significantly inhibited the macromolecular permeability increasing effect of histamine (343.5 +/- 22.3 versus 207.5 +/- 32.0 leaks/cm2; P < 0.01), bradykinin (345.2 +/- 19.0 versus 206.2 +/- 21.6 leaks/cm2; P < 0.01), and LTB4 (353.3 +/- 27.5 versus 242.7 +/- 33.6 leaks/cm2; P < 0.05). At reperfusion, after thirty minutes of ischemia, S 5682 significantly decreased the observed macromolecular permeability (103.6 +/- 15.4 versus 42.6 +/- 9.3 leaks/cm2; P < 0.01). Flavonoid-treated animals also displayed a statistically significant lower number of adhering leukocytes to the venular endothelium (83.5 +/- 9.5 versus 48.4 +/- 12.3 per 6 mm2; P < 0.05). These results demonstrate that oral administration of S 5682 for ten days at 20 mg/kg body weight/day had a protective effect against leakage of macromolecules after application of permeability-increasing substances and during ischemia-reperfusion in the cheek pouch microvasculature. Since firm leukocyte attachment to the endothelial wall and subsequent emigration of leukocytes into the interstitium is a mechanism for tissue damage during inflammation, attenuation of this phenomenon during conditions of ischemia-reperfusion can in part explain previous observations that this purified micronized flavonoid fraction decreases edema formation. The present data illustrating the inhibitory effect of a clinically relevant dose of S 5682 on the inflammatory processes induced in this in vivo model of microcirculation may serve as a rational basis to explain its clinical efficacy.

Angiology. 1997 Jan;48(1):77-85.
Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients.
Guilhou JJ1, Dereure O, Marzin L, Ouvry P, Zuccarelli F, Debure C, Van Landuyt H, Gillet-Terver MN, Guillot B, Levesque H, Mignot J, Pillion G, Février B, Dubeaux D.

The objective of this study was to evaluate the efficacy of Daflon 500 mg (Dios)* in venous ulcers. A multicenter, double-blind, randomized, controlled versus placebo (Plac) trial was conducted, with stratification according to the size of ulcer (< or = 10 cm and > 10 cm). The protocol called for a two-month treatment with Dios (one tablet = 450 mg micronized purified Diosmin) or a placebo, two tablets/day, in addition to compression therapy. Evaluations were performed every fifteen days, from D0 to D60. The primary endpoint, in accordance with Alexander House group requirements were: percentage of patients with complete ulcer healing, ie, comparison between Dios and Plac group at D60, and comparison of survival curves in each group between D0 and D60 (log rank test). Secondary endpoints included ulcer surface area assessed by computerized planimetric measurements, qualitative evaluation of ulcers, and symptoms. The patients were 105 men and women ranging in age from eighteen to eighty-five years, with standard compression stocking, who were undergoing standardized local care of ulcer and had no significant arterial disease (ankle/arm systolic pressure index > 0.8). Fifty-three patients received Dios, and 52 received Plac. The 2 groups were well matched for age (m +/- 1 SD = seventy-one +/- eleven years), gender, ulcer size, and associated disorders. Among patients with ulcer size < or = 10 cm (Dios = 44, Plac = 47) a significantly larger number of patients had a complete ulcer healing at two months in the Dios group (n = 14) in comparison with the Plac group (n = 6) (32% vs 13%, P = 0.028) with a significantly shorter time duration of healing (P = 0.037). No difference was shown for the secondary criteria, except for sensation of heavy legs (P = 0.039) and a less atonic aspect of ulcer (P = 0.030) in favor of Dios. Among the 14 patients with ulcer size > 10 cm (Dios = 9, Plac = 5), subjected to a descriptive analysis only, no ulcer healed. This study showed that a two-month course of Daflon 500 mg at a daily dose of two tablets, in addition to conventional treatment, is of benefit in patients with venous ulcer < or = 10 cm by accelerating complete healing.

Int Angiol. 1995 Sep;14(3 Suppl 1):8-13.
The human saphenous vein in pharmacology: effect of a new micronized flavonoidic fraction (Daflon 500 mg) on norepinephrine induced contraction.
Juteau N1, Bakri F, Pomies JP, Foulon C, Rigaudy P, Pillion G, Lange G, Genre O, Cron JP.

Local acidosis (pH 6.4) depresses reactivity of vascular smooth muscle and especially the response of human isolated saphenous veins to exogenous norepinephrine. Experiments were performed to study, under acidosis conditions, the interaction between Daflon 500 mg, a micronized fraction of 90% diosmin and 10% hesperidin, and norepinephrine on human rings of veins. Varicose veins were obtained by conservative varicose veins surgery and normal veins from patients undergoing coronary artery bypass graft surgery. Isometric tension was recorded from venous rings in organ chambers filled with Krebs-Henseleit solution (pH 7.4; 37 degrees C). Metabolic acidosis (from pH 7.4 to 6.4) was obtained by lowering the HCO3- concentration of the Krebs-Henseleit solution. Cumulative concentration-response curves for norepinephrine (10(-7) to 10(-5)M) were obtained at pH 6.4 in the presence or in the absence of Daflon 500 mg (10(-5)M) added 20 min previously to the organ bath. Under acidotic conditions, Daflon 500 mg induced a shift to the left of the concentration-response curves for norepinephrine. This potentiation was significant in both normal and varicose veins and was increased in proportion with the pathological status of the venous rings. These results support the therapeutic benefits of Daflon 500 mg in chronic venous insufficiency.

Int J Microcirc Clin Exp. 1995;15 Suppl 1:22-6.
Effects of Daflon 500 mg on increased microvascular permeability in normal hamsters.
Bouskela E1, Donyo KA, Verbeuren TJ.

Daflon 500 mg1 (S 5682) is a purified, micronized, flavonoid fraction containing 90% diosmin and 10% hesperidin, which is currently used to treat chronic venous insufficiency and haemorrhoidal disease. In the present study, the effects of Daflon 500 mg on increased microvascular permeability induced by histamine, bradykinin and leukotriene B4 (LTB4) were investigated by intravital microscopy in the hamster cheek pouch preparation. Daflon 500 mg, suspended in 10% lactose solution, or vehicle (10% lactose) was administered orally to male hamsters for 10 days at a dose of 20 mg/kg/day (10 mg/kg twice daily). Fluorescein isothiocyanate-labeled dextran 150 was given intravenously, 30 min after completion of the cheek pouch preparation. Histamine, 2 mumol/l, bradykinin, 0.1 mumol/l, and LTB4, 0.01 mumol/l, applied topically for 5 min increased the number of fluorescent vascular leakage sites in postcapillary venules. The maximum number of leaky sites per cm2 in the prepared area that occurred 5 min after the beginning of each topical application was quantified by UV light microscopy. In comparison with vehicle, Daflon 500 mg significantly inhibited the macromolecular permeability-increasing effect of histamine (343.5 +/- 22.3 vs. 207.5 +/- 32.0; p < 0.01), bradykinin (345.2 +/- 19.0 vs. 206.2 +/- 21.6; p < 0.01) and LTB4 (353.3 +/- 27.5 vs. 242.7 +/- 33.6; p < 0.05). These results demonstrate that oral administration of Daflon 500 mg for 10 days at 20 mg/kg body weight/day has a protective effect against leakage of macromolecules after application of permeability-increasing substances in the cheek pouch microvasculature. These data, which illustrate the inhibitory effect of a clinically relevant dose of Daflon 500 mg on the inflammatory processes induced in this in vivo model of microcirculation, may serve as a rational basis to explain the clinical efficacy of Daflon 500 mg.

Int J Microcirc Clin Exp. 1995;15 Suppl 1:17-21.
Cellular basis of inflammation, edema and the activity of Daflon 500 mg.
Friesenecker B1, Tsai AG, Intaglietta M.

Inflammation activates leukocytes causing the release of agents that disrupt the endothelial barrier to such an extent that retention of plasma protein is impaired. This phenomenon can be observed using microvascular methods in which ischemia-reperfusion-induced inflammation-like condition are analyzed in terms of the increased adherence of leukocytes to the venular endothelium. Pretreatment with Daflon 500 mg, a purified, micronized, flavonoid fraction consisting of 90% diosmin and 10% hesperidin, prior to the induction of 4 h of tourniquet ischemia significantly lowers the number of adherent leukocytes. This observation is linked to the protective effect of flavonoids in the treatment of edema, as decreased activation is also associated with a decreased platelet and complement system activation, leading to a lowered release of histamine and decreased leukocyte-dependent endothelial damage. It is proposed that attenuation of leukocyte adherence during ischemia-reperfusion is evidence of the protective endothelial effect of Daflon 500 mg and its ability to control edema in clinical situation.

Angiology. 1994 Jun;45(6 Pt 2):579-84.
Safety and security of Daflon 500 mg in venous insufficiency and in hemorrhoidal disease.
Meyer OC1.

Daflon 500 mg is a new flavonoid vasoprotector venotonic agent whose active principle is micronized and contains 90% diosmin and 10% flavonoids expressed as hesperidin. In animal studies, the safety of Daflon 500 mg is shown by an LD50 (lethal dose 50) of more than 3 g/kg, ie, 180 times the daily therapeutic dose, as well as by the absence of any toxic effect after repeated oral dosing for thirteen and twenty-six weeks, using a dose representing 35 times the daily dosage, in the rate and primate. Daflon 500 mg has no mutagenic action nor any significant effect on reproductive function. Gastrointestinal tolerance is good when administered orally in the rat. Transplacental passage and passage into breast milk are minimal. In the rat, 0.003% of the administered dose has been found in each fetus and 1% in breast milk. Clinical trials fulfill international scientific requirements and have collected more than 2850 patients treated with Daflon 500 mg at the dosage of two tablets per day for six weeks to one year. The proportion of patients with side effects (10% of those treated), essentially of a gastrointestinal or autonomic nature and leading to a rate of only 1.1% trial dropouts, is less than described in 225 patients given a placebo (13.9%) in controlled trials. Satisfactory clinical acceptability already confirmed in the short term was equally found in long-term treatment. Hemodynamic parameters (systolic and diastolic blood pressure) as well as laboratory parameters (hematology, liver and renal function, metabolic) were uninfluenced even by prolonged treatment for one year at the dosage of two tablets per day.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiology. 1994 Jun;45(6 Pt 2):549-53.
Controlled studies of Daflon 500 mg in chronic venous insufficiency.
Geroulakos G1, Nicolaides AN.

Although great advances have been made in the operative treatment of vascular disorders, the management of most venous problems is still nonsurgical. Daflon 500 mg* is a micronized flavonoid mixture of 90% diosmin and 10% hesperidin that has phlebotonic properties. The efficacy of Daflon 500 mg has been investigated in three double-blind, randomized trials using strain gauge plethysmography to provide quantitative information on venous hemodynamics in patients with chronic venous insufficiency. In total, 183 patients were treated with Daflon 500 mg versus a control group of equal number of patients. Daflon 500 mg produced a significant decrease in venous capacitance, venous distensibility, and venous emptying time (P < 0.001). In addition, these changes were accompanied by improvement in clinical symptoms and a decrease in the supramalleolar circumference. Clinical side effects were rare and led to treatment withdrawal in only 3 patients. It is concluded that Daflon 500 mg is of benefit to patients with chronic venous insufficiency.

Angiology. 1994 Jun;45(6 Pt 2):554-9.
Mediators involved in inflammation: effects of Daflon 500 mg on their release.
Jean T1, Bodinier MC.

Each step of an inflammatory reaction is triggered by one or several chemical or biological mediators such as arachidonic acid derivatives (prostaglandins [PG], leukotrienes [LT], or thromboxanes [TX]), vasoactive amines (histamine or serotonin), and oxygen free radicals (superoxide ion, O2-, or hydrogen peroxide, H2O2). In perivenous inflammation, these mediators play a prominent role in favoring vasodilatation (histamine), increasing membrane permeability (PGE2, histamine, free radicals) and providing a chemotactic signal for specialized cells, ie, neutrophil polynuclears, macrophages, lymphocytes (LTB4, free radicals). The antiinflammatory effects of Daflon 500 mg,* a micronized purified flavonoid fraction (90% diosmin, 10% hesperidin), were studied in different in vivo and in vitro models. In a model of inflammatory granuloma in the rat, Daflon 500 mg (100 mg/kg, orally) reduced edema formation and inhibited the synthesis for PGE2 (78.5%), PGF2 alpha (45.2%) and TXB2 (59.5%) (Damon et al, Arzneim-Forsch/Drug Res 37:1149-1153, 1987). Intravenous injection of Daflon 500 mg (25 and 50 mg/kg) reduced the hyperglycemia induced by injection of alloxan in rat. This effect of Daflon 500 mg was linked to its ability to scavenge active oxygen radicals, demonstrated in vitro using human neutrophils (Lonchampt et al, Arzneim-forsch/Drug Res 39:882-885, 1989) or mouse peritoneal macrophages (Bodinier et al, manuscript in preparation) stimulated by zymosan. The free radical scavenger effect of Daflon 500 mg is observed at concentrations ranging from 10(-7) M to 10(-4) M, with half-maximal effect between 10(-6) M and 10(-5) M. Thus, Daflon 500 mg behaves as a potent protective agent against inflammatory disorders. These properties may explain, at least in part, the clinical activity of Daflon 500 mg and justify its therapeutic use.

Int Angiol. 1993 Mar;12(1):69-72.
A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility.
Galley P1, Thiollet M.

The efficacy and safety of a new veno-active flavonoid fraction (S 5682) consisting of micronized diosmin (90%) and hesperidin (10%) have been studied in 100 patients with symptomatic capillary fragility in a double-blind, randomized, placebo-controlled trial. Treatment lasted 6 weeks and consisted of 2 daily tablets of either S 5682 or placebo. Patients were examined at weeks 0, 2, 4 and 6. Compared to placebo, capillary resistance, assessed by the negative suction cup method, was significantly higher in the S 5682 group at week 4 (219 +/- 10 mmHg versus 159 +/- 8 mmHg; p < 0.001) and week 6 (261 +/- 12 mmHg versus 163 +/- 9 mmHg; p < 0.001). This resulted in a significant improvement of symptoms of capillary fragility (spontaneous ecchymosis, epistaxis, purpura, petechiae, gingivorrhagia, metrorrhagia and conjunctival haemorrhage) in S 5682 treated patients (p < 0.001). S 5682 was well tolerated. The rate of side-effects spontaneously volunteered by the patients was similar in both groups. We, therefore, conclude that S 5682 increases to a large extent the capillary resistance in patients with abnormal capillary fragility without significant side-effects.
 
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Well @Stilgar

No
But i took vitamin k nd never fixed the problem

Nowadays im taking niacinamide

Whenevwr i have gut issues
The varicose vein appear

Now i fixed my gut issues and no more varicose vein
 

Nikki

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"The presence of PR in the media of saphenous veins suggests that progesterone may influence venous structure and/or function. Physiological venous changes have been described on the basis of hormonal status, such as venous stasis during luteal phase or pregnancy. Consequently, venous blood flow may be directly modulated by steroid hormones. Changes in uterine blood flow, known to occur in the cycling uterus or during pregnancy,41 were previously shown to be directly modulated by steroid hormones via their specific receptors (ER and PR) present in vascular smooth muscle cells.6 7 In particular, the presence of PR staining in smooth muscle cells of spiral arteries in early pregnancy7correlates with large increases in endometrial and myometrial blood flow that occur to support fetal growth and homeostasis. The role of progesterone in the saphenous vein remains to be determined. We have reported preliminary data on the in vitro progesterone-induced decrease of noradrenaline and calcium-induced contractions from isolated human saphenous veins.42 Whether or not progesterone has also an effect on the structure of the vein via a regulation of cell proliferation remains unknown."



Is it possible that high adrenaline is masking your possibly damaged leg veins and when you administer progesterone is it reduced and the varicose veins become prominent?

"Its actions are to increase peripheral resistance via α1 receptor-dependent vasoconstriction"

It sounds like a reasonable suspicion since I have suffered from anxiety for much of my life. However, if this were the case, I would think the veins would no longer be visible or would shring to some degree when progesterone therapy was halted. Your thoughts?

@goodandevil, I haven't emailed Ray about it yet, but am tempted to.

@Stilgar, my protein intake is pretty high, I think. I eat a good amount of meat, eggs, and dairy.

@charmer- That is an interesting hypothesis. I definitely wasn't taking it consistently this last time. If that would cause estrogen spikes, then that could be the problem. However, the first time I tried it, I was pretty consistent and that's when the veins first surfaced.

I haven't read through all of the posts yet, so I'll be back later to finish up. Thank you all for your help!
Happy New Year!
 

Nikki

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Well i donno

But for me its related to estrogen

I have big varicose in my left calf

When i have high serotonin
And bloating and indegestion

It appears

So for me
Aspirine worked like charm
For varicose

But
It caused me a very bad ulcer and bleeding in my stomach for 1 month

Are you having diarrhea?
Pain and fatigue in feet ,back and hands every now and then ?


Hi. Sorry it took me so long to get back to this. I didn't see you had questions at the end. I rarely have intestinal upset. If anything, things move too slowly and I am dependent on magnesium supplementation.

I did start taking a buffered aspirin twice a day recently and think it caused a GI bleed so I had to stop. For those of you prone to aspiring bleeds, or any bleeds, please research and stock up on Yunnan Paiyao, it could save your life. I didn't know it could help with spider/vericose veins. If I can figure out how to balance aspiring with K2 to prevent bleeds (anyone have tips?), I would like to get back on it.

I don't have any pain in my feet or hands on any regular basis or for unknown reasons (e.g they will hurt if I injure them of course). I do have numbness in my feet at times which seems circulation related. I have issues tolerating "cold" temperatures. I'm not sure if this ties in. I am not taking thyroid becasue my ND said my levels were good, but I am tempted to take it anyway.

Thanks for helping me get to the bottom of this.
 

Nikki

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I think the mechanism Stryker posted may be relevant for some individuals - you may be interested in the citrus flavonoids Diosmin and Hesperidin, which help to maintain venous tone.

Clinically there is a preparation of those flavonoids called Daflon but supplements of micronized Diosmin/Hesperidin are available as well.

Angiology. 1994 Jun;45(6 Pt 2):531-6.
Advantage of a micronized flavonoidic fraction (Daflon 500 mg) in comparison with a nonmicronized diosmin.
Amato C1.

...

This is very helpful. I started taking Rutin recently in hopes to support my kidneys (labs show reduced GFR). Do you think Rutin could work similarly? Or, do you think the Daflon or micronized Diosim, could provide the same benefit as the Rutin so that I could take just one or the other? The micronized option sounds more effective, so I will try to source them. I take so many supplements, I don't know how I could take any more so I would like to streamline and see if there aren't some which would "kill two birds", so to speak. It seems in some articles Rutin and Diosim are comparable so I will just take whichever one is most bioavailable and cost effective. I would still be too nervous to take progesterone without some way of testing it's effects. Any suggestions on how to proceed cautiously?
 

Koveras

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This is very helpful. I started taking Rutin recently in hopes to support my kidneys (labs show reduced GFR). Do you think Rutin could work similarly? Or, do you think the Daflon or micronized Diosim, could provide the same benefit as the Rutin so that I could take just one or the other? The micronized option sounds more effective, so I will try to source them. I take so many supplements, I don't know how I could take any more so I would like to streamline and see if there aren't some which would "kill two birds", so to speak. It seems in some articles Rutin and Diosim are comparable so I will just take whichever one is most bioavailable and cost effective. I would still be too nervous to take progesterone without some way of testing it's effects. Any suggestions on how to proceed cautiously?

The reduced GFR (glomerulus filtration rate) is likely another symptom of the same issue as the glomerulus in the kidneys is a network of capillaries, so leaky capillaries without appropriate tone are likely to affect both the kidney function as well as the function of the leg veins and other tissues and organs in the lower half of the torso where blood pooling is more likely. The flavonoids may help. Citrus fruits and marmalade have a flavonoid content that is much lower (but broader in variety) than supplements and still likely to be relevant if consumed regularly.
 

Nikki

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I just wanted to say I wasn't taking a high dose of K ona daily basis. I was taking an ADEK complex (breakdown below). I didn't take extra K2 to counter the aspirin until I noticed the blood. I took one big dose of extra K2 and was fine by the next day, but of course I stopped the aspiring. For the aspirin, I don't think the dose was high at all. I was only taking 325 mg tabs and only 1-4 per day. I would only take 4 in a day if I had a headache, otherwise it was usually one in the AM and one in the afternoon. I feel like I need to be on aspirin, but now I'm nervous about it.

Something interesting happened while I was taking the aspirin. I had recently resumed iodine supplementation at the time I started supplementing aspirin daily. 3 "pre cancerous" (or cancerous? they were not biopsied) spots which I had been treating for months made a rapid improvement in just a week's time. I am not sure if it was the aspirin or the iodine, or the combination of both since both have cancer fighting properties. I am hoping it was the iodine, since I can continue that without issue. I'm taking only 1/2 of an iodoral tablet (whole tab is 12.5mg).
 

Nikki

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The reduced GFR (glomerulus filtration rate) is likely another symptom of the same issue as the glomerulus in the kidneys is a network of capillaries, so leaky capillaries without appropriate tone are likely to affect both the kidney function as well as the function of the leg veins and other tissues and organs in the lower half of the torso where blood pooling is more likely. The flavonoids may help. Citrus fruits and marmalade have a flavonoid content that is much lower (but broader in variety) than supplements and still likely to be relevant if consumed regularly.

Brilliant! I didn't even see the connection. It's been so many years since I studied anatomy and physiology and I forgot that the glomeruli were little batches of capilaries.
 

Mito

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I am not sure if it was the aspirin or the iodine, or the combination of both since both have cancer fighting properties.
Ray talks a lot about the cancer fighting properties of aspirin and there has been quite a few posts on this forum about it. I didn't know iodine had cancer fighting properties. It seems like when Ray talks about iodine, it's mostly warning about not supplementing with too much of it.
 

raysputin

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I also developed spider veins taking progestE. I am 26. I also gained about 20 lbs and my cellulite increased A LOT so in terms of it improving muscle tone and vascularity I think it really depends on the person and their current state of health.
 
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