OHIO RESEARCH GROUP
Ziegenfuss T.N., Mendel R.W., and Hofheins J.E. Safety and Efficacy of a Naturally-Occurring, Orally Administered, Aromatase Inhibitor in Healthy Men. Ohio Research Group of Exercise Science and Sports Nutrition. Wadsworth, Ohio 44281, USA. n tim@ohioresearchgroup.com This email address is being protected from spam bots, you need Javascript enabled to view it
Rationale: In healthy men, it is known that blocking estrogen formation stimulates the HPT axis to increase in vivo testosterone production. Recently, a new class of dietary supplements has appeared that claim to inhibit the aromatase enzyme (i.e., decrease the transformation of aromatizable androgens [androstenedione, DHEA, testosterone] into estrogens [estriol, estrone, estradiol]), thus stimulating an increase in testosterone formation.
Purpose: The purpose of this pilot study was to examine the effects of a popular aromatase inhibitor, Novedex XTÔ (NOV-XT), on selected hormonal responses (total testosterone [TT], bioavailable testosterone [BT] and estradiol [E2]), as well as serum and plasma markers of renal, hepatic, and hematological function.
Methods: Using an open-label, proof-of-concept design, five eugonadal men (mean ± SD age, height, weight, body fat: 31.6 ± 2.8 yr, 174.3 ± 1.8 cm, 84.3 ± 3.8 kg, 11.2 ± 3.3 %) ingested 4 capsules of NOV-XT prior to bed for 28 consecutive days. According to the manufacturer, each capsule of NOV-XT contains 60 mg of a proprietary blend of three naturally-occurring aromatase inhibitors: 6, 17-keto-etiocholeve-3-ol tetrahydropyranol, 3, 17-keto-etiochol-triene, and 3’,5,7-trihydroxy-4’-methoxyflavone (supplements were provided by an FDA-registered, pharmaceutically licensed manufacturer; confirmation by an external laboratory is pending). Blood samples obtained at baseline (prior to supplementation), and at weekly intervals thereafter for 28 days, were analyzed for TT, BT, and E2 by radioimmunometric and chemilluminetric assays. Subjects were required to maintain their normal dietary and training patterns during the study. All blood samples were obtained at the same time of day (0700-0900) to minimize diurnal variation. Hormone concentrations were statistically analyzed by ANOVA and Tukey’s HSD post-hoc test. Dependent t-tests were used to compare changes in blood chemistries. Statistical significance was accepted at p<0.05.
Results: Compared to baseline, NOV-XT administration rapidly and significantly increased TT and BT. Mean changes from baseline for TT after one, two, three, and four weeks of NOV-XT administration were: +145% (p<0.006), +183% (p<0.0005), +232% (p<0.0002), and +240% (p<0.0002), respectively. Mean changes from baseline for BT after one, two, three, and four weeks of NOV-XT administration were: +300% (p<0.01), +402% (p<0.0009), +511% (p<0.0002), and +528% (p<0.0002), respectively. Despite these large increases in TT and BT, no significant aromatization to estradiol occurred (i.e., E2 concentrations remained unchanged). No significant changes in clinical blood chemistries (fasting glucose, BUN, creatinine, bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, sodium, potassium, chloride, calcium, albumin, globulin, CO2, total protein, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol) or systemic hemodynamics (heart rate, systolic blood pressure, diastolic blood pressure) were observed, nor were any adverse events noted during the study.
| Variable | Baseline | Day 7 | Day 14 | Day 21 | Day 28 |
| Testosterone (ng/dL) | 517 (162) | 1265 (252) * | 1515 (212) * | 1714 (322) * | 1758 (435) * |
| Bio T (ng/dL) | 159 (57) | 636 (265) * | 798 (94) * | 971 (226) * | 998 (210) * |
| Estradiol (pg/mL) | 22 (3) | 19 (9) | 16 (9) | 19 (11) | 19 (9) |
| Glucose (mg/dL) | 90 (4) | | | | 87 (10) |
| BUN:Cr | 17 (5) | | | | 17 (4) |
| Bilirubin (mg/dL) | 0.8 (0.5) | | | | 0.9 (0.5) |
| ALP (IU/L) | 84 (32) | | | | 67 (43) |
| AST (IU/L) | 27 (7) | | | | 27 (8) |
| ALT (IU/L) | 29 (11) | | | | 31 (15) |
| Chol (mg/dL) | 156 (19) | | | | 163 (27) |
| TAG (mg/dL) | 74 (22) | | | | 72 (19) |
| HDL (mg/dL) | 54 (3) | | | | 51 (9) |
| LDL (mg/dL) | 87 (18) | | | | 97 (20) |
| SBP (mm Hg) | 124 (5) | | | | 124 (11) |
| DBP (mm Hg) | 75 (6) | | | | 74 (14) |
Data are reported as mean (± SD). * indicates significantly different from corresponding baseline value. Bio T = bioavailable (free+weekly bound) testosterone, BUN:Cr = blood urea nitrogen:creatinine ratio, ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine aminotransferase, Chol = total cholesterol, TAG = triglycerides, HDL = high density lipoprotein, LDL = low density lipoprotein, SBP = systolic blood pressure, DBP = diastolic blood pressure.
Conclusions: Within the framework of the current experimental design, these preliminary data indicate that four weeks of NOV-XT supplementation significantly elevates serum TT and BT, likely via the inhibition of estradiol formation. Further, NOV-XT does not appear to result in any deleterious effects on blood chemistry or systemic hemodynamics in healthy, eugonadal men. Future research is necessary to confirm and refine these results in a larger sample size, as well as examine the impact of NOV-XT on androgenic and estrogenic metabolites, body composition, and muscular performance. Supported in part by a research grant from Gaspari Nutrition (Neptune, NJ).
BAYLOR UNIVERSITY STUDY
Willoughby D. S., & Wilborn C. Eight weeks of
aromatase inhibition using the nutritional supplement Novedex XT: Effects on serum steroid hormones, body composition, and clinical safety markers in young, eugonadal males. International Journal of Sports Nutrition and Exercise Metabolism.
Manuscript Accepted for February 2007 Publication.
In yet another (the 3rd) independent clinical research study, Novedex XT® shows why it is rightfully known as the #1 Testosterone Modulating Supplement of All Time and why it is the #1 Selling Testosterone Modulating Supplement... EVER! No other “supposed testosterone modulating” supplement has even one, never mind THREE (3) independent clinical research studies conducted on it to demonstrate that it works and is safe like Novedex XT® does. If the other guy’s supplements do not have any studies to show their product works, how do they know it works? More importantly, how do YOU know it works? Who wants to spend hard earned money for a “maybe?” In this landmark 11 week independent clinical trial conducted by Dr. Darryn Willoughy at Baylor University, Novedex XT® did not cause any significant changes in any Serum Clinical Chemistry Markers (including liver studies and cholesterol/HDL/LDL) or Urine Clinical Safety Markers or even in PSA – a significant clinical marker for prostate health! But Novedex XT® did cause an average of 600%+ increase in free testosterone! This change is so dramatic that if you are a “tested athlete” we strongly suggest that you discuss use of Novedex XT® with your sanctioning body before using it. With results this powerful, you might be wrongfully accused of “cheating.” Even more importantly, all of the clinical parameters checked, including LH/FSH and GH, everything returned back to baseline (normal) levels within 21 days of discontinuation of Novedex XT® showing that even using Novedex XT™ for 60 days straight does not “shut you down” when you come off of it.
Figure Legends
Figure 1. Serum total testosterone levels over the course of the 11 weeks. A group x time interaction was observed
(p = 0.001). * denotes a significant increase for the
Novedex group compared to placebo at the 4- and 8-week sampling period.
Figure 2. Serum free testosterone levels over the course of the 11 weeks. A group x time interaction was observed
(p = 0.001). * denotes a significant increase for the
Novedex group compared to placebo at the 4- and 8-week sampling period.
Figure 3. Serum free testosterone/estradiol ratio (T/E) levels over the course of the 11 weeks. A group x time interaction was observed (p = 0.002). * denotes a significant increase for the Novedex group compared to placebo at the 4- and 8-week sampling period.
Table 1. Four-Day Dietary Analyses for the Placebo and Novedex Groups During Weeks 0, 8, and 11.
| Variable/Group | Week 0 | Week 8 | Week 11 |
| | | | |
| Protein (g/kg) | | | |
| Placebo | 1.9 ± 1.0 | 2.4 ± 1.6 | 2.4 ± 1.4 |
| Novedex | 2.5 ± 0.8 | 2.7± 1.1 | 2.6 ± 0.9 |
| | | | |
| Fat (g/kg) | | | |
| Placebo | 1.7 ± 0.5 | 1.5 ± 0.5 | 1.3 ± 0.8 |
| Novedex | 1.7 ± 1.6 | 1.3 ± 0.6 | 1.2 ± 0.49 |
| | | | |
| Carbohydrates (g/kg) | | | |
| Placebo | 2.3 ± 0.6 | 2.2 ± 0.6 | 2.3 ± 0.7 |
| Novedex | 2.6 ± 1.3 | 2.8 ± 1.3 | 2.8 ± 1.5 |
| | | | |
| Total Calories (kcal/kg) | | | |
| Placebo | 26 ± 6.0 | 28 ± 8.0 | 28 ± 6.0 |
| Novedex | 31 ± 10.0 | 31 ± 8.0 | 31 ± 9.0 |
Data are means and ± standard deviations. No significant differences were observed between groups throughout the 11-week study for total calories or macronutrient intakes (p > 0.05).
Table 2. Serum Hormones Values for the Placebo and Novedex Groups at Weeks 0, 4, 8, and 11.
| Variable/Group | Week 0 | Week 4 | Week 8 | Week 11 |
| | | | | |
| PSA (ng/ml) | | | | |
| Placebo | 3.41 ±0.57 | 3.54 ±0.61 | 3.68 ±0.55 | 3.43 ±0.49 |
| Novedex | 3.27 ±0.56 | 3.53 ±0.62 | 3.37 ±0.64 | 3.14 ±0.28 |
| | | | | |
| Estrone (pg/ml) | | | | |
| Placebo | 361.19 ±63.71 | 395.05 ±124.31 | 392.02 ±173.80 | 410.32 ±150.63 |
| Novedex | 405.10 ±167.07 | 430.74 ±85.40 | 433.89 ±118.46 | 431.04 ±153.04 |
| | | | | |
| Estradiol (pg/ml) | | | | |
| Placebo | 63.00 ±50.29 | 54.33 ±38.21 | 58.33 ±37.18 | 56.77 ±36.92 |
| Novedex | 78.00 ±80.89 | 91.62 ±101.11 | 102.50 ±124.95 | 75.25 ±73.96 |
| | | | | |
| Estriol (pg/ml) | | | | |
| Placebo | 0.06 ±0.03 | 0.10 ± 0.05 | 0.12 ±0.04 | 0.13±0.05 |
| Novedex | 0.07 ±0.04 | 0.07 ± 0.05 | 0.10 ±0.02 | 0.11±0.04 |
| | | | | |
| FEI | | | | |
| Placebo | 4.11 ±4.61 | 4.08 ±5.25 | 4.45 ±5.34 | 4.05 ±4.45 |
| Novedex | 4.28 ±4.30 | 5.72 ±5.31 | 6.43 ±6.58 | 4.19 ±2.96 |
| | | | | |
| SHBG (pg/ml) | | | | |
| Placebo | 18.17 ±5.27 | 17.25 ±5.07 | 17.07 ±5.21 | 17.56 ±5.74 |
| Novedex | 19.18 ±7.98 | 16.49 ±7.27 | 16.22 ±8.15 | 18.11 ±8.29 |
| | | | | |
| LH (pg/ml) | | | | |
| Placebo | 3.53 ±1.46 | 4.66 ±2.05 | 4.41 ±1.93 | 3.44 ±1.64 |
| Novedex | 3.98 ±2.19 | 4.56 ±2.29 | 4.11 ±2.85 | 3.25 ±2.11 |
| | | | | |
| FSH (pg/ml) | | | | |
| Placebo | 19.34 ±29.03 | 20.22 ±29.89 | 18.16 ±26.85 | 18.12 ±27.03 |
| Novedex | 9.04 ±14.75 | 10.30 ±17.07 | 9.75 ±16.72 | 7.98 ±13.21 |
| | | | | |
| Cortisol (pg/ml) | | | | |
| Placebo | 32.73 ±5.69 | 31.86 ±9.05 | 29.80 ±6.11 | 31.06 ±6.59 |
| Novedex | 30.93 ±5.06 | 29.26 ±6.76 | 33.16 ±6.42 | 31.70 ±5.00 |
| | | | | |
| GH (pg/ml) | | | | |
| Placebo | 111.98 ±141.79 | 63.38 ±120.91 | 83.11 ±114.62 | 101.46 ±144.48 |
| Novedex | 81.59 ±118.49 | 30.92 ±18.68 | 59.52 ±75.13 | 58.42 ±120.46 |
Data are means ± standard deviations. No significant differences were observed between groups throughout the 11-week study for and of the hormones variables included above (p > 0.05).
Table 3. Body Composition Values for Total Body Mass, Total Body Water, Percent Fat, and Fat-Free Mass for the Placebo and Novedex Groups at Weeks 0, 4, 8, and 11.
| Variable/Group | Week 0 | Week 4 | Week 8 | Week 11 |
| | | | | |
| Total Body Mass (kg) | | | | |
| Placebo | 87.62 ±10.44 | 87.76 ±10.29 | 87.62 ±10.06 | 88.19 ±11.17 |
| Novedex | 95.83 ±17.61 | 96.70 ±16.96 | 95.63 ±16.83 | 95.97 ±17.22 |
| | | | | |
| Total Body Water (kg) | | | | |
| Placebo | 48.94 ±4.67 | 49.38 ±3.86 | 49.32 ±3.99 | 50.81 ±5.34 |
| Novedex | 54.06 ±9.48 | 56.05 ±8.95 | 56.62 ±7.91 | 55.69 ±7.85 |
| | | | | |
| Body Fat (%) | | | | |
| Placebo | 18.40 ±6.32 | 19.04 ±6.30 | 18.66 ±6.49 | 19.10 ±6.96 |
| Novedex | 16.01 ±5.57 | 15.78 ±5.70 | 15.26 ±5.27 | 15.61 ±5.58 |
| | | | | |
| Fat-Free Mass (kg) | | | | |
| Placebo | 71.07 ±5.80 | 70.64 ±5.86 | 70.85 ±5.68 | 70.87 ±6.43 |
| Novedex | 80.10 ±13.21 | 81.11 ±13.16 | 81.47 ±12.95 | 80.63 ±13.31 |
Data are means ± standard deviations. No significant differences were observed between groups throughout the 11-week study for total body mass, total body water, or fat-free mass (p > 0.05).
