Well you SAY its 110, yet from all the feedback ive seen from Free test no one is getting the joint issues usually associated with low cort/low estrogen, yet with Erase it has happened at 75.
To me it sounds like its really not dosed accordingly, and as long as its hidden within a prop blend ill continue to feel this way.
And nonetheless, it isnt just 110mg VS 75. Free test costs more, and while it may have additional ingredients, not all of them are beneficial. Take forskolin for example, it is shown in literature to upregulate aromatase. I wouldnt pay more for that.
Resveratrol has been shown in several studies to have some positive effects on cartilage- this is one of the reasons I included it in the formulation, along with quercetin to prevent the glucorinidation of res-v. I noticed a pretty significant reduction in joint pain when I took a decent dose of res-v/quercetin a few years ago when I was taking 6-Bromo (it kills my joints), so when were developing the product, it seemed like a logical choice to try in a beta. The first beta for Free Test didn't contain res-v and quercetin, and it was dosed around 140 mg/4 capsules- 5 out of 5 testers had to quit taking it because it was murdering their joints. The second beta had res-v and quercetin along with a 120 mg/4 capsule dose, and only 1 person out of 10 complained of joint pain.... here are a couple studies- not great because they were animal studies- but they are directional:
Biochem Pharmacol. 2008 Dec 1;76(11):1426-39. Epub 2008 Jun 3.
Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis.
Shakibaei M, Csaki C, Nebrich S, Mobasheri A.
SourceLudwig-Maximilians-University Munich, Faculty of Medicine, Institute of Anatomy, Musculoskeletal Research Group, Pettenkoferstrasse 11, D-80336 Munich, Germany.
[email protected]
Abstract
Osteoarthritis is an inflammatory disease of load-bearing synovial joints that is currently treated with drugs that exhibit numerous side effects and are only temporarily effective on pain, the main symptom of the disease. Consequently, there is an acute need for novel, safe and more effective chemotherapeutic agents for the treatment of osteoarthritis and related arthritic diseases. Resveratrol is a phytoalexin stilbene produced naturally by plants including red grapes, peanuts and various berries. Recent research in various cell models has demonstrated that resveratrol is safe and has potent anti-inflammatory properties. However, its potential for treating arthritic conditions has not been explored. In this study we provide experimental evidence that resveratrol inhibits the expression of VEGF, MMP-3, MMP-9 and COX-2 in human articular chondrocytes stimulated with the pro-inflammatory cytokine IL-1beta. Since these gene products are regulated by the transcription factor NF-kappaB, we investigated the effects of resveratrol on IL-1beta-induced NF-kappaB signaling pathway. Resveratrol, like N-Ac-Leu-Leu-norleucinal (ALLN) suppressed IL-1beta-induced proteasome function and the degradation of IkappaBalpha (an inhibitor of NF-kappaB) without affecting IkappaBalpha kinase activation, IkappaBalpha-phosphorylation or IkappaBalpha-ubiquitination which suppressed nuclear translocation of the p65 subunit of NF-kappaB and its phosphorylation. Furthermore, we observed that resveratrol as well as ALLN inhibited IL-1beta-induced apoptosis, caspase-3 activation and PARP cleavage in human articular chondrocytes. In summary, our results suggest that resveratrol suppresses apoptosis and inflammatory signaling through its actions on the NF-kappaB pathway in human chondrocytes. We propose that resveratrol should be explored further for the prophylactic treatment of osteoarthritis in humans and companion animals.
Arthritis Res Ther. 2010;12(5):R167. Epub 2010 Sep 8.
Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes.
Liu FC, Hung LF, Wu WL, Chang DM, Huang CY, Lai JH, Ho LJ.
SourceGraduate Institute of Medical Science, National Defense Medical Center, Neihu 114, Taipei, Taiwan, ROC.
Abstract
INTRODUCTION: Accumulation of advanced glycation end products (AGEs) in joints contributes to the pathogenesis of cartilage damage in osteoarthritis (OA). We aim to explore the potential chondroprotective effects of resveratrol on AGEs-stimulated porcine chondrocytes and cartilage explants.
METHODS: Chondrocytes were isolated from pig joints. Activation of the IκB kinase (IKK)-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)-activator protein-1 (AP-1) pathways was assessed by electrophoretic mobility shift assay (EMSA), Western blot and transfection assay. The levels of inducible nitric oxide synthase (iNOS)-NO and cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) were measured by Western blot, Griess reaction or ELISA. The expression and enzyme activity of matrix metalloproteinase-13 (MMP-13) were determined by real time RT/PCR and gelatin zymography, respectively.
RESULTS: We show that AGEs-induced expression of iNOS and COX-2 and production of NO and PGE2 were suppressed by resveratrol. Such effects of resveratrol were likely mediated through inhibiting IKK-IκBα-NF-κB and JNK/ERK-AP-1 signaling pathways induced by AGEs. By targeting these critical signaling pathways, resveratrol decreased AGEs-stimulated expression and activity of MMP-13 and prevented AGEs-mediated destruction of collagen II. Histochemistry analysis further confirms that resveratrol could prevent AGEs-induced degradation of proteoglycan and aggrecan in cartilage explants.
CONCLUSIONS: The present study reveals not only the effects and mechanisms regarding how resveratrol may protect cartilage from AGEs-mediated damage but also the potential therapeutic benefit of resveratrol in the treatment of OA.
Spine (Phila Pa 1976). 2008 Nov 15;33(24):2586-95.
The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc.
Li X, Phillips FM, An HS, Ellman M, Thonar EJ, Wu W, Park D, Im HJ.
SourceDepartment of Biochemistry, Section of Rheumatology, Rush University Medical Center, Chicago, IL 60612, USA.
Abstract
STUDY DESIGN: Basic science, biologic study.
OBJECTIVE: To determine the potential benefits of using resveratrol (RSV) for intervertebral disc (IVD) matrix repair and regeneration.
SUMMARY OF BACKGROUND DATA: The phytoestrogen RSV is a natural compound found in various plants including grapes and red wines. RSV has been reported to provide a protective effect on articular cartilage in rabbit models for arthritis, but its effect on spine cartilage is unknown. METHODS.: We studied the effect of RSV on bovine IVD cartilage homeostasis by assessing MMP-13 (potent catabolic factor) production, proteoglycan (PG) accumulation and synthesis, and the interaction between RSV and known catabolic factors such as bFGF or IL-1. To understand the molecular mechanisms by which RSV modulates MMP-13 and PG production, we also investigated its downstream target regulatory molecules.
RESULTS: Stimulation of bovine disc cells cultured in monolayer with bFGF or IL-1 augmented the production of MMP-13 and ADAMTS-4 at the transcriptional level and this augmentation was blocked by RSV. Incubation of nucleus pulposus cells with RSV for 21 days significantly increased PG accumulation per cell in a dose-dependent manner, increased PG synthesis, rescued PG losses induced by catabolic reagents bFGF and IL-1, and promoted cell survival to levels seen after incubation with the anabolic protein BMP7 100 ng/mL. Protein-DNA interaction array results suggest that RSV effectively suppresses downstream target molecules of bFGF and IL-1 responsible for oxidative stress, proliferation, and apoptosis.
CONCLUSION: Resveratrol is a potent anabolic mediator of bovine IVD cartilage homeostasis, revealing its potential as a unique biologic treatment to slow the progression of IVD degeneration. These data suggests RSV may have considerable promise in the treatment of disc degeneration.
A good Forskolin study:
Obes Res. 2005 Aug;13(8):1335-43.
Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese men.
Godard MP, Johnson BA, Richmond SR.
SourceUniversity of Kansas, Department of Health, Sport and Exercise Sciences, Applied Physiology Laboratory, Lawrence, KS 66045, USA.
[email protected]
Abstract
OBJECTIVE: This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese (BMI > or = 26 kg/m(2)) men.
RESEARCH METHODS AND PROCEDURE: Thirty subjects (forskolin, n = 15; placebo, n = 15) were studied in a randomized, double-blind, placebo-controlled study for 12 weeks.
RESULTS: Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage (BF%) and fat mass (FM) as determined by DXA compared with the placebo group (p < or = 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12-week trial compared with the placebo group (p < or = 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p = 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p < or = 0.05). The actual change in serum total testosterone concentration was not significantly different among groups, but it increased 16.77 +/- 33.77% in the forskolin group compared with a decrease of 1.08 +/- 18.35% in the placebo group.
DISCUSSION: Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12-week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.