In today’s post we talked about the implementation of Immun’Âge® fermented papaya extract in menopause.

Inquiring from the grassroots

In the reproductive phase, women experience cyclical changes in the ovaries and uterus, and it is hormones that regulate these changes.
Menopause is defined as the permanent loss of menstruation after 12 months of amenorrhea. Menopause symptoms can be psychologically distressing, especially since they occur at a time when women play important roles in society, family, and the workplace.
The hormonal changes that begin during the menopausal transition affect many biological systems.
Consequently, the signs and symptoms of menopause include disorders related to the central nervous system, metabolic, cardiovascular, musculoskeletal changes, and sexual dysfunction. The physiological basis of these manifestations is somewhat complex and is related, but not limited to, estrogen deprivation.

Menopause is also linked to an imbalance in oxidative stress due to decreased estrogen production. According to some studies, menopause is likely to be associated with a deterioration of redox balance due to a concomitant decrease in antioxidant capacity and an increase in oxidative stress phenomena.
This redox imbalance affects several target organs to different degrees and is related to the cardiovascular risk marker.

The decrease in circulating estrogens is estimated to be one of the causative factors of this disorder, especially with regard to cardiovascular health and very recently it has been suggested that a new membrane-bound receptor, i.e., the G-protein-coupled estrogen receptor, which mediates non-genomic actions of 17β-estradiol, may play a key pathogenic role. https://doi.org/10.1152/ajpheart.00430.2018

Why are there more risks?

Menopause is a risk factor for cardiovascular disease because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism.
Menopause aggravates many traditional risk factors for cardiovascular disease, including:

• Changes in body fat distribution from a gynoid pattern to an android pattern
• Reduced glucose tolerance
• abnormal plasma lipids
• increased blood pressure
• Increased sympathetic tone
• endothelial dysfunction and vascular inflammation

A 1976-1994 study of 35,616 postmenopausal women found an overall significant association between earlier age at menopause and an increased risk of coronary heart disease among women who experienced menopause and never used hormone replacement therapy.
This increased risk was seen among current smokers, but not among those who never smoked.
This same study indicates that exogenous estrogen use among postmenopausal women has been consistently associated with a reduced risk of coronary heart disease.
DOI:10.1001/archinte.159.10.1061

These changes in adipose tissue can lead to increased insulin resistance (up to 50%) in postmenopausal women compared to premenopausal women.
ERα and ER type β (ERβ) promote β cell survival and secretion.
Pancreatic insulin secretion is also reduced by 50% in postmenopausal women compared to premenopausal women, regardless of BMI and age.
DOI: 10.1111/j.1365-2362.1993.tb00792.x

Regarding blood pressure, epidemiological evidence suggests an increase after the onset of menopause.
However, it is unclear whether this is a consequence of menopause per se or the ageing process, due to reduced vascular elasticity and increased prevalence of atherosclerosis at older ages.
The contribution of other factors, such as obesity, smoking, and low physical activity, should be taken into account.
In any case, a more pronounced increase in systolic blood pressure has been reported in postmenopausal women. https://doi.org/10.1161/01.HYP.0000124670.03674.15

In addition, a recent meta-analysis showed a slight but significant increase in the risk of high blood pressure in women compared to those with a menopausal age greater than 45 years.
Plausible pathogenic mechanisms include the production of vasoconstrictor factors, such as endothelin and angiotensinogen, as a result of decreased estrogen concentrations, and a lower estrogen-to-androgen ratio during menopause. https://doi.org/10.1111/j.1463-1326.2005.00545.x

What is Immun’Âge®?

Immun’ Âge® is a fermented papaya preparation developed by the Osato Research Institute in Japan.
It is made from non-genetically modified papayas that are purchased from contract farmers in the U.S.
It is a 100% natural food product made with patented technology and without side effects or toxicity after 20 years on the market.
Fermented papaya extract helps stimulate the body’s natural defenses and provides energy.

The product promotes the expression of the GSTM1 gene supporting Phase II liver detoxification, helps to reduce oxidative stress, eliminating excess free radicals and stimulating antioxidant enzymes such as SOD (Superoxide Dismutase) and GPX (Glutathione Peroxidase).
Common antioxidants are often overused and can be converted into pro-oxidants. Immun’Âge® stimulates the endogenous production of antioxidant enzymes, so antioxidant production responds based on oxidative demand, making this product unique for the regulation of oxidative stress.

Immun’Âge and menopause

To test the efficacy of the aforementioned treatment, a study was designed that included 74 non-smoking postmenopausal women (time greater than one year since the last menstruation), with a body mass index of 21-29 kg/m2, with stable body weight in the month prior to the trial (±1 kg).
In addition, these patients were on traditional hormone replacement therapy or with bioidentical hormones, without steroids, without the intake of food supplements, without a vegan diet or high intake of dietary fiber or fermented foods (>400 g/day).
Major past or ongoing illnesses were considered exclusion criteria, along with alcohol, drug abuse, or use during the past 3 months of prebiotics, probiotics, alone, or as food fortification or antibiotics.

Patients were divided into two groups of 37 participants each, matched by age, length of menopausal diagnosis, BMI, dietary intake, and physical activity measured in kcal/week, while instructed to refrain from intense physical exercise.
Treatment assignments followed computer-generated randomization sequences.
Supplementation was carried out as follows: group A was left without supplementation and group B: it was supplemented with fermented papaya 4.5 grams 2 times a day, administered sublingually in the morning and approximately 2 hours after lunch.
The treatments were maintained for 6 months.
Another separate group (Group C) consisting of 25 menopausal women not treated with any hormone replacement, served as a control.

This study demonstrated that supplementation with fermented papaya produced a significant improvement of all redox parameters at the 6-month follow-up visit regardless of BMI and from the third month observation.
Given the high confirmed safety profile of the supplement even in older people, the evidence-based nutraceutical intervention shown above may provide a valid opportunity within a broader strategy of health promotion and disease prevention in menopausal women.
DOI: 10.4172/2167-065X.1000193

Another study, which aimed to test a functional food (in this case fermented papaya) on redox and mitochondrial efficiency in postmenopausal women, included a study population of 69 postmenopausal women.
They were not under any hormone replacement treatment and were divided into three groups: group A received a multivitamin 2 times a day and group B received 4.5 g of fermented papaya 2 times a day.
Group C consisted of 23 fertile premenopausal women as a control group.

The tests performed at admission and at 3 and 6 months were erythrocyte redox parameters, oxidized proteins in plasma, cerebral neurotrophic factor, and Vmax activity of cytochrome C oxidase in the mitochondria of peripheral blood mononuclear cells.
Menopausal women showed an increase in malondialdehyde that normalized with both treatments, but the multivitamin failed to do so in the BMI subgroup ≥26.

All other redox enzymes were significantly lower in menopausal women and responded only to papaya supplementation. Cyclooxygenase-citrate synthase activity was significantly reduced.
Although these data are preliminary, they confirm the redox and mitochondrial dysfunction that occurs in postmenopause and responds adequately to supplementation with fermented papaya, but inadequately to high doses of antioxidants.
DOI: 10.23812/19-315-A

Conclusion

At Salengei we are dedicated to the permanent search for natural solutions that are beneficial, but with zero – or at least minimal – side effects.
That is why we are convinced that a product based on fermented papaya such as Immun’Âge®, solves our questions, provides proven benefits and would not cause side effects in its consumers.

This complete product not only provides cardiovascular results in postmenopausal women, correcting redox levels, but, within its range of benefits in oxidative regulation, significant improvements are seen in many other metabolic processes.
Various positive results can be seen in a wide range of diseases such as respiratory diseases, aging (especially of the skin), Alzheimer’s disease, atrophic gastritis, liver disorders (including alcohol withdrawal) and hypothyroidism, all of which have a large deleterious oxidative component.