Ferula Max

Take one (1) capsule by mouth for 7 consecutive days. After the first week, reduce to one (1) capsules taken every other day, with 48 hours between doses (3 times in the second week). Follow this schedule for the remainder of your product. After completing one cycle (one box), discontinue use for at least 30 days. If you wish to resume after your 30 day off-cycle, follow the same directions. Do not exceed suggested use.

Ferula Max is a potent extract of Ferula hermonis, sourced from the mountains of Hermon in Syria; it is not a novel intervention despite being unfamiliar to most people. There is an ancient use history dating back centuries as a male aphrodisiac in the Levantine region. 

In 2007, Hedaya and colleagues found for the first time that consumption of this plant significantly increases total testosterone in diabetic males enrolled in a randomized controlled trial. Their study enrolled 60 married diabetic males (type 2 diabetes mellitus) with erectile dysfunction, aged 40 - 55, divided into three treatment groups of: placebo, 500mg of dried alcoholic extract of Ferula hermonis daily, and 1000mg daily, over 8 weeks. Both treatment groups showed statistically significant increases in total testosterone of +47% at 500 mg daily and +145.66% at 1000mg daily (both administered for 8 weeks) with dose dependent effects (p < 0.05). Estradiol also increased significantly in both treatment groups. Erectile function (IIEF-5) and Rigiscan nocturnal tumescence parameters improved significantly in both treatment groups; duplex ultrasound showed no significant differences. Lipid changes were significant only at the 1000mg dose; total cholesterol decreased by 23.3%, triglycerides by -22.69% and LDL by -26.52% (p < 0.05). ALT, AST, blood glucose, and body weight showed no statistically significant changes in any group (Hedaya et al., 2007). 

Adapted from "Evaluation of the clinical effect of Zallouh extract (Ferula hermonis) on diabetic patients with erectile dysfunction," by Hedaya et al., 2007, Tanta University, 18(1). 

Table 1: Mean changes in biochemical tests following eight weeks of Ferula hermonis extract administration in group 1 (control group), group 2 and group 3 of Ferula Hermonis administration - Adapted from "Evaluation of the clinical effect of Zallouh extract (Ferula hermonis) on diabetic patients with erectile dysfunction," by Hedaya et al., Tanta University, 2007, 18(1) 

* Significant difference after Ferula hermonis extract administration compared with their respective values before extract administration (paired t-test, P < 0.05) 

We were able to independently support these findings qualitatively in healthy males, a distinct population different from the parent study. We observed every single volunteer experience a supraphysiological increase in their total testosterone levels which exceeded our expectations. The results from Hedaya et al. (2007) were consistent with our observations, it became evident that Ferula hermonis administration increases endogenous testosterone production in males with functioning gonads; Hedaya & colleagues utilized appropriate methodology to quantify the change in the approximate range of +50–150% from baseline. 

We investigated additional outcomes including: 

• Sex hormone binding globulin (SHBG) 

• LH and FSH 

• Estradiol 

• Anecdotal reports of physical performance 

• Anecdotal reports of sexual performance 

Among our volunteers, total testosterone became consistently elevated in supraphysiological ranges of 1000 to 1200 ng/dL following supplementation. Even 20 days after discontinuation, testosterone remained above baseline, taking approximately 30 days for endocrine markers to reach homeostasis. A practical estimation can be extrapolated that the duration to reach homeostasis divided by 5 is roughly equal to the half-life of the active components (in this case, ~6 days). More extensive pharmacokinetic trials are required to determine the true half-life; however there is great probability that there is a half-life of several days given the many days to reach biochemical homeostasis after washout and symptomatic resolution in the case reported below of the post menopausal woman who had tried Ferula Hermonis root extract. 

We noted a markedly increased testosterone to estrogen ratio, which contradicted the findings in the 2007 RCT by Hedaya et al. 

Sex hormone binding globulin increased significantly, which prevented a supraphysiological rise in free testosterone. Older volunteers had a greater rise in SHBG than younger volunteers. 

Co-administration with DHEA and boron could provide a benefit to decrease the rate of rise of SHBG significantly (Bello 2018, Morales 1998); the degree to which cannot be quantified as individual response could vary greatly based on each unique biophysical profile and lifestyle factors 

Administration of Ferula Max will reduce free DHT levels significantly. Administration of DHEA may partially mitigate this effect if it is not intended. There have been no reports of hair loss or acne with administration of this root extract; in theory, it should be protective against these outcomes. 

Transaminases did not show any elevations in our cohort, consistent with the findings of Hedaya et al. (2007). 

We observed a significant decrease in LDL cholesterol to the healthy range in those who had chronically elevated LDL at baseline (also consistent with the findings of Hedaya and colleagues). This effect only lasted for as long as the supplement was being administered and did not persist through the 30 days of discontinuation. 

Volunteers reported improvements in strength performance, averaging approximately 20 lb increases on major compound lifts. Libido and erectile function appeared to improve within the first week, though these effects subsequently returned toward baseline. This was not performed in a double-blinded or placebo controlled methodology. Each volunteer was used as their own control and followed periods of dose escalation, discontinuation and restarting administration of Ferula Max; measuring the response to each manipulation of the intervention. The lack of placebo and blinding is indeed a limitation, with optimism, this limitation may serve to increase the external validity of the findings as it more closely mimics what would likely happen in a non experimental setting. The magnitude of effect and very low likelihood of achieving supraphysiologic testosterone levels spontaneously make it unlikely for the findings to be explained by artifact/bias from a practical perspective (or from exogenous use of testosterone. LH / FSH were assessed showing no arguing against AAS, showing a concordant rise of testosterone and gonadotropin release). 

The sole purpose of our observational effort was to know, there are many different ways to know something. We felt it was appropriate to use a pragmatic epistemic framework to determine whether the results from Hedaya et al were authentic/can be replicated to any degree. The findings benefited in the ability to generate new hypotheses and discussion of pharmacology, informing the development of highly effective botanical interventions. 

At markedly high doses, some volunteers experienced a slight decrease in testosterone levels with still a notable rise in LH. The observed effects appeared to follow a U-shaped dose response curve. Based on these findings, Ferula Max should not be taken continuously year-round, given the possibility of cumulative effects and dose stacking with prolonged use. The long apparent duration of endocrine effects further strengthens the recommendation for periods of discontinuation. Ferula Max should be used in cycles only. 

One of the most consistent findings was a marked reduction in estradiol among our volunteers. This directly contradicts the findings of Hedaya et al. (2007), where estradiol increased with the intervention. 

Commentary for those interested in this finding: One possible explanation is that differences in extraction methods may produce different ratios of active components including ferutinin, teferidin, and teferin; likely resulting in different hormonal effects. Mechanistically, this may reflect unidentified aromatase inhibition or downregulation of aromatase expression directly due to administration to this preparation of Ferula Hermonis. If it is later confirmed that this effect on estradiol was mediated by aromatase inhibition, this would increase the strength of the recommendation to coadminister with DHEA for the purposes of increasing androgen levels in males; given that the conversion of DHEA to androstenedione to testosterone will be disproportionately higher than their conversion to estrogen, the testosterone to estrogen ratio would be further amplified without inducing negative feedback to the hypothalamic gonadal axis. 

No trial to date has shown that DHEA administration in isolation leads to meaningful changes in male testosterone levels. However, this is not the case with females; DHEA is well established to be effective for increasing total and free androgens in women (Morales et al., 1998). 

LH was found to be markedly elevated above reference ranges after the intervention; with an LH Max in one volunteer of 14.6 IU/L and corresponding Total Testosterone of 1061ng/dL (baseline LH: 3.1IU/L, total testosterone : 527ng/dL). FSH did not rise and slightly decreased on Ferula Max in every volunteer. This was a fascinating finding that contributes to the understanding of the mechanism; it generates a hypothesis that this extract is an antagonist of the estrogen receptor on the LH/GnRH axis but agonist of the estrogen receptor on the FSH suppressing (activin) pathway at the pituitary. It is highly probable that the other non ferutinin components of Ferula Hermonis such as teferdin or teferin have other distinct endocrine effects and they are very similar to ferutinin structurally. 

As demonstrated by Zanoli et al. (2005), finding that both ferutinin and teferdin acutely increased testosterone levels; in the acute setting ferutinin promoted male mating behaviors and raised androgen levels, but when taken chronically it had a paradoxical effect. 

Conversely for Teferdin, there were no chronic suppressive effects on androgenic activity noted and it continued to maintain elevated testosterone levels and improved male mating behaviors in rats. 

Figure 1, 2 & 3 | Difference in bioactive components in the Ferula Hermonis adapted from Zanoli, P., Rivasi, M., Zavatti, M., Brusiani, F., Vezzalini, F., & Baraldi, M. (2005). Activity of single components of Ferula hermonis on male rat sexual behavior. International Journal of Impotence Research, 17(6), 513–518. 

The significance of this pre clinical trial is in demonstrating independent acute testosterone stimulating effects of Ferutinin and Teferdin administered in isolation; noting a subchronic suppressive effect of ferutinin, with no subchronic suppressive effects of Teferdin or Teferin. This suggests a complex interplay of the active ingredients in the full spectrum extract and the potential to develop different concentrates of the Ferula Hermonis to achieve distinct physiologic outcomes. 

Different extraction methods and hypothesis testing are ongoing to determine if different pharmacological effects can be achieved with different standardizations of the fascinating Ferula hermonis root. 

Our extract does not contain ferutinin in isolation and also has a high percent of teferdin. The composition of the extract is an important factor in the net outcomes. The dosage instructions follow a staggered frequency of three times per week (after the loading phase); mitigating the risk of supra therapeutic levels and chronic toxicity. We found this dosing frequency to be the most effective in increasing testosterone levels even if taken for 30 days; with no lab findings of suppression noted and a full recovery to baseline of all endocrine markers even after multiple cycles in volunteers. The Hedaya trial administered Ferula hermonis extract daily for 8 weeks without any suppression to testosterone levels or clinical reports of decreased sexual function (instead, noting improvements). 

A postmenopausal woman took Ferula Max at 500 mg once daily and noted within four days the onset of pelvic pressure and cervical mucus discharge. It was discontinued immediately, and it took a total of 10 days for symptoms to completely abate. It cannot be ruled out that endometrial proliferation was occurring, suggesting estrogen like activity in the endometrium. Ferula Max should not be taken by women due to the risks of unopposed estrogen activity. There are no studies examining the safety of this ingredient in women (although there is one human trial on Ferula communis, standardized for 20 mg of ferutinin administered for 90 days in post menopausal women, showing compelling outcomes in effectively treating vasomotor symptoms with no adverse events noted); all data on females as it pertains to ferula hermonis is derived from preclinical outcomes in animals. 

Premenopausal women should not take this, as the effect on this population has not been formally established. It may cause hyperovulation or disrupt the menstrual cycle; its teratogenic potential is unknown. If conception were to occur while on the supplement, there is no established safety profile for maternal or neonatal outcomes. We strongly recommend avoiding this product if you are assigned female at birth. 

Ferula hermonis undoubtedly contains potent selective estrogen receptor modulator compounds with mixed agonist and antagonist properties. Ferula Max maintains the traditional full spectrum profile in which the root is consumed as a whole. There are ongoing efforts to utilize HPLC fractionation and other methods to precisely isolate the primary active components of this herb, as the full spectrum root contains many bioactive ingredients which likely have independent physiological effects, isolating the most selective bioactive compounds and characterizing their effects remains a work in progress. 

References

1. Bello, M., Guadarrama-Garcia, C., Velasco-Silveyra, L. M., Farfan-Garcia, E. D., & Soriano-Ursua, M. A. (2018). Several effects of boron are induced by uncoupling steroid hormones from their transporters in blood. Medical Hypotheses, 118, 78–83. https://doi.org/10.1016/j.mehy.2018.06.024
2. Hedaya, M. A., Hegazy, S. K., Salem, K. A., & Abd El-Kawy, K. S. (2007). Evaluation of the clinical effect of Zallouh extract (Ferula hermonis) on diabetic patients with erectile dysfunction. Tanta University. https://kfs.edu.eg/staff_site/abstracts/Evaluation%20of%20the%20Clinical%20Effect%20of%20Zallouh%20Extract%20(Ferula%20Hermonis)%20on%20Diabetic%20Patients%20with%20Erectile%20Dysfunction.pdf
3. Morales, J., Haubrich, R. H., Hwang, J. Y., Asakura, H., & Yen, S. C. (1998). The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clinical Endocrinology, 49(4), 421–432.
4. Zanoli, P., Rivasi, M., Zavatti, M., Brusiani, F., Vezzalini, F., & Baraldi, M. (2005). Activity of single components of Ferula hermonis on male rat sexual behavior. International Journal of Impotence Research, 17(6), 513–518
5. Macrì, R., Maiuolo, J., Scarano, F., Musolino, V., Fregola, A., Gliozzi, M., Carresi, C., Nucera, S., Serra, M., Caminiti, R., Cardamone, A., Coppoletta, A. R., Ussia, S., Ritorto, G., Mazza, V., Bombardelli, E., Palma, E., Muscoli, C., & Mollace, V. (2024). Evaluation of the Potential Beneficial Effects of Ferula communis L. Extract Supplementation in Postmenopausal Discomfort. Nutrients, 16(16), 2651. https://doi.org/10.3390/nu16162651

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