Metabolic health is intertwined with a woman’s health from her reproductive years through menopause and beyond. About 36.6% of women in the United States have metabolic risk factors and poor insulin sensitivity, underscoring the need to support metabolic health in the female population.1 In women, poor insulin sensitivity often goes hand in hand with increased production and inefficient clearance of key androgenic hormones like testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEA-S), which can further throw menstrual cycles and ovulation off balance.2
Unfortunately, difficulty conceiving affects 12.7% of women in the United States, while 25% of diagnosed infertility cases can be traced back to poor ovarian health.3 Insulin and blood sugar balance is not only critical for heart health, it’s also important for ovarian function, egg quality, and fertility. Furthermore, metabolic health and hormonal balance are important for menstrual cycle regularity, fertility, and they help to avoid common symptoms associated with menopause, such as hot flashes, mild mood changes, and sleep disturbances.
Achieving optimal female health and metabolic function requires an intricate balance between three interconnecting areas of health:
1) Insulin sensitivity
2) Hormonal balance
3) Mitochondrial health and antioxidant defenses
To answer this need, DaVinci® Laboratories created Inositol + Vitex Plus, a combination of natural insulin-sensitizing and ovarian health agents for women.* This science-backed supplement contains ingredients like 2,000 milligrams (mg) of myo-inositol to support ovarian function, menstrual cycle regularity, balanced testosterone, and fertility.* It delivers 400 mg of Vitex agnus castus (VAC, chasteberry) to support reproductive health during a menstrual cycle and even after menopause by improving mood, decreasing breast tenderness, and helping to reduce cramps, bloating, and hot flashes. CoQ10 at 100 mg and alpha-lipoic acid (ALA) at 250 mg support mitochondrial health of oocytes and counteract oxidative stress.* ALA is also a powerful tool for insulin sensitivity and quenching free radicals, while chromium (250 mcg) boasts insulin-sensitizing properties as well.* This article will review the ingredients and the science behind Inositol + Vitex Plus, a novel women’s health formula.* Women of all ages now have access to powerful and effective ingredients in a convenient capsule to help maintain their hormonal, metabolic, and reproductive health.*
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• Maintains /supports balanced testosterone levels*
• Healthy ovaries*
• A calm, balanced mood*
• Reduction in common symptoms associated with a normal menstrual cycle
• Helps maintain more regular menstrual cycles*
• Helps reduce cramps and bloating*
• Helps to decrease breast tenderness*
• Fertility support*
• Supporting optimal insulin sensitivity*
• Mitochondrial rejuvenation in oocytes*
• Helps reduce the frequency of hot flashes*
• Improved sleep and vaginal lubrication during menopause
Insulin sensitivity is critical for supporting ovarian health and menstrual cycle regularity, and therefore healthy fertility. Insulin resistance is a complex metabolic concern, manifesting in a variety of conditions, with no single etiological pathway.4 For millions of years, insulin has worked in humans and other organisms to take energy during times of plenty and store it for later use. In a healthy person, blood sugar levels increase with a meal and insulin is released. It helps to take up carbohydrates and convert carbohydrates and protein into lipids for storage.5 However, in insulin resistance, cell receptors are no longer responsive to insulin. Higher levels of insulin are secreted, yet blood sugar levels remain high. Reactive oxygen species and oxidative stress play a role in insulin resistance, damage to beta cells, and poor glucose tolerance.6 Insulin resistance can lead to a variety of issues related to metabolism and hormone balance.*
Insulin production inhibits ovarian follicle growth, which can lead to anovulation.7 Ovarian follicles are fluid-filled sacs that each contain an egg and are therefore necessary for female fertility. Insulin also interacts with luteinizing hormone, a hormone that stimulates ovulation in females. The interaction between insulin and luteinizing hormone results in increased production of testosterone in women7, which affects ovarian health.
Myo-inositol, alpha-lipoic acid, and chromium are all included in Inositol + Vitex Plus for their well-researched ability to support healthy insulin and blood sugar levels already in the normal range.* By doing so, these powerful insulin-sensitizing agents maintain ovarian health.*
Myo-inositol is involved in insulin signaling and glucose metabolism.*8 It supports healthy blood sugar in women and maintains balanced insulin levels.*8 Inositol isoforms like myo-inositol regulate insulin activity in many target organs, including the ovaries.*9
Myo-inositol is a derivative of inositol hexakisphosphate, a component of fiber-rich foods that have a high-content of phytic acid or phytate. Living cells also produce myo-inositol. 8 However, people with insulin resistance have an increased urinary excretion of myo-inositol.8
Myo-inositol significantly helps reduce duodenal glucose absorption and helps keep blood sugar levels stable.*10 Conversely, glucose can also block cellular uptake of inositol.8
Clinical studies in women demonstrate that myo-inositol supplementation supports insulin sensitivity and maintains stable blood sugar,11 which can assist with enhancing fertility.* It can also maintain healthy blood sugar metabolism in pregnant women.*11-13
Myo-inositol is used in the formula due to the abundance of research on this form of inositol along with concerning effects of D-chiro inositol when used alone without myo-inositol.14 Women who have less than optimal insulin sensitivity are thought to have an accelerated conversion of myo-inositol into D-chiro inositol, which leads to increased production of D-chiro inositol and a myo-inositol deficiency in the ovary.*14 Too high an amount of D-chiro inositol can worsen oocyte quality and ovarian response.*14
Alpha-lipoic acid (ALA) is another insulin-sensitizer used to support healthy glucose metabolism.* It is an organosulfur compound located in the mitochondria of cells where it participates in energy production and powerfully quenches free radicals.* 15 It’s used to promote ovarian health and has been used together with metformin to improve outcomes of assisted reproductive technologies (ART), including a significant increase in the number of maturated oocytes and the rate of fertilization.*16 In a clinical study, ALA supported healthy insulin sensitivity and helped maintain a more regular menstrual cycle.*17 Other benefits of ALA for women's health will be discussed later in this article.
Chromium is included in Inositol + Vitex Plus® due to its well-recognized role in insulin sensitivity and the metabolism of proteins, lipids, and carbohydrates.*18 An essential micronutrient for humans, chromium promoted healthy glucose metabolism and a balanced inflammatory response in 40 women undergoing in vitro fertilization (IVF).*19 A systematic review and meta-analysis found that in two studies investigating a total of 81 women, chromium resulted in a significantly better Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) compared to the placebo group.*20 Another study found chromium supplementation resulted in better measurements on the Homeostatic Model Assessment-beta-cell function (HOMA-B) compared to women taking a placebo.*20 Chromium helped reduce oxidative stress and increased antioxidants in animal models.6
Hormonal balance is key to many aspects of both female and male health. In women, balanced levels of testosterone are important to ovarian health, ovulation, and menstrual cycle regularity.*21 Healthy fertility and ovarian function also requires balanced levels of other androgenic hormones, such as androstenodione and DHEA-S.* Insulin insensitivity increases production of testosterone. When testosterone, androstenedione, and DHEA-S are out of balance, it can also promote acne, oily skin, unexpected body hair, irregular menses, or even baldness.* High DHEA can promote the apoptosis of ovarian granulosa cells and stimulate the inflammatory response.22
Prolactin, another important hormone in women’s health, is responsible for lactation and breast tissue development.* High levels can affect menstrual regularity and fertility.* Beyond testosterone and androgenic hormones, maintaining balance of other sex hormones such as progesterone and estrogen sets the stage for a normal menstrual cycle and health during menopause.*
Research in women found that myo-inositol can support healthy testosterone levels with a corresponding increase in sex-hormone binding globulin (SHBG).* 23 SHBG binds excess testosterone, lowering the amount of free testosterone available for body tissues to use.*
The combination of inositol and folic acid in women given for six months significantly reduced hormones such as prolactin, androstenedione, free and total testosterone, and luteinizing hormone along with an increase in SHBG.*24 These changes were accompanied by improvements in the HOMA index and glycemic control.* In a similar study using myo-inositol and folic acid in women, testosterone levels fell from 96.6 ng/mL to 43.3 ng/mL and progesterone increased from a mean of 2.1 ng/mL to 12.3 ng/mL after 12 weeks.*25 Myo-inositol resulted in excellent fertilization rates and a clear trend to a better embryo quality compared to placebo.*
In a meta-analysis, there was a slight trend toward reducing testosterone in women given myo-inositol compared to controls.14 Androstenedione levels did not change. In a subgroup, a significant increase in serum SHBG only occurred in studies where women took myo-inositol for at least 24 weeks.14
Myo-inositol and alpha-lipoic acid both help promote regular menstrual cycles and ovulation.* A meta-analysis of randomized trials including a total of 362 women taking inositol (257 on myo-inositol, 105 on di-chiro-inositol) found that inositol significantly improved ovulation rate and supported menstrual cycle regularity compared with placebo.*26
Other research investigated the use of myo-inositol plus folic acid on women undergoing IVF treatment.25 Two groups of women received supplements for two months before starting IVF: one group of 15 women received a placebo and one group of 14 women received myo-inositol plus folic acid. Of the women taking myo-inositol plus folic acid, 70% had their ovulation restored.* The ratio of follicle/retrieved oocyte was clearly better in the myo-inositol group. Out of the 233 oocytes retrieved in the myo-inositol group, 136 were fertilized whereas only 128 out of 300 oocytes were fertilized in the placebo group. Oocyte and embryo quality were better in the myo-inositol group than in the placebo group.*
Combining ALA with myo-inositol is an effective strategy to optimize the menstrual cycle.* A combination of either 2,000 mg or 1,000 mg of myo-inositol and 800 mg of ALA for six months led to an improvement in cycle regularity in 71.2% of the women.*27 Women taking the 2,000 mg dose of myo-inositol had a better improvement in menstrual regularity compared with the 1,000 mg dose.* The beneficial effects of this combination did not seem to be related to insulin.
A key component of DaVinci’s Inositol + Vitex Plus is Vitex agnus castus, also known as chasteberry, and referred to as “VAC” here. Various studies have confirmed that VAC can help improve common concerns that occur during the menstrual cycle.*28-30 VAC has helped to alleviate occasional irritability, moodiness, anger, headaches, bloating, tiredness, drowsiness, and sleeplessness that occur as part of the menstrual cycle.*31 In one study, by the third menstrual cycle of use, 91% of the women taking VAC responded to the supplement and nearly all of the women were without symptoms or experiencing only mild symptoms.*31
In another study, 52% of women given VAC responded to the supplement after taking it for three consecutive cycles.29 The women reported improvements in:
• Anger*
• Breast fullness*
• Headaches*
• Irritability*
• Mood alterations*
• Other menstrual concerns, including bloating*
VAC may also be effective in breast tenderness associated with the menstrual cycle.* One
double-blind, placebo-controlled study noted this effect in 48 women given VAC compared to 49 given a placebo for three consecutive menstrual cycles.32 The intensity of the breast tenderness was reduced faster in the VAC group compared to placebo.*
The leaves and flowers of VAC contain some compounds that have a similar structure to the sex hormones.29 Its mechanism of action may also involve regulation of stress-induced prolactin secretion via dopamine, without directly affecting luteinizing hormone or follicle-stimulating hormone.33,34
Not only helpful for menstruating women, Vitex agnus castus in Inositol + Vitex Plus by DaVinci Laboratories supports the health of menopausal women.* An eight week, double-blind, randomized, placebo-controlled study included 46 women aged 40 to 60 years who were experiencing an average of more than four hot flashes per day.35 The women took a combination of VAC and Nigella sativa daily together with a medication for hot flashes. This combination was shown to be significantly better for hot flashes compared to the medication alone.35
An investigation of a topical VAC essential oil in menopausal women found that it could help to minimize hot flashes or night sweats, maintain emotional stability, support mild age-related cognitive function, improve vaginal tone and lubrication, and support a regular menstrual cycle.*36
Controlling androgen levels with myo-inositol continues to be useful during and after menopause, as well as during childbearing years.37 Myo-inositol may support the health of postmenopausal women, who sometimes experience disrupted androgen levels, causing unwanted hair growth.* In menopausal women, estrogen levels may be imbalanced due to aromatization of androgens into estrogens, without the normal opposition of progesterone.38 Myo-inositol’s insulin-sensitizing properties are also beneficial for heart health during aging.*39
Addressing insulin balance and hormone balance goes far to improve a woman’s fertility outcomes. However, there is one more critical but under-recognized determinant of reproductive health. Oxidative stress and mitochondrial dysfunction are thought to play an important role in declining ovarian reserve and oocyte quality.40
Poor mitochondrial health could explain age-dependent decline in ovarian reserve and oocyte quality. Oocytes have the largest number of mitochondria of any cell in the body.41 Furthermore, there is a correlation between low mitochondrial DNA (mtDNA) copy number and fertilization of oocytes.42 Indeed, oocytes of women who have ovarian insufficiency have a lower mtDNA copy number compared with women with healthy functioning ovaries.43
Mitochondria produce approximately 90% of reactive oxygen species (ROS) and neutralize ROS via antioxidant defense mechanisms.44 If ROS production increases in the mitochondria of oocytes and early embryos, it overwhelms the antioxidant defense, contributes to mitochondrial dysfunction, and increases oxidative stress. This damages DNA and other cellular components. Poor blood sugar regulation also contributes to oxidative stress, mitochondrial dysfunction, and can affect fertility and birth outcomes.41
Improving mitochondrial function by supplementing with antioxidants like coenzyme Q10 is one of the ways in which women can enhance reproductive and metabolic health.*41 CoQ10 is a critical part of the inner mitochondrial membrane, where it’s involved in electron transport in the mitochondrial respiratory chain and oxidative phosphorylation to generate adenosine triphosphate (ATP).* CoQ10 acts as an antioxidant by suppressing lipid peroxidation and DNA oxidation, and therefore shores up endogenous antioxidant defense within a cell.*
A decline in CoQ10 levels is common in individuals in their late 30s and occurs together with the age-related decline in fertility. Its declining presence is associated with chromosomal alterations in the embryo, suggesting that the reduced expression of CoQ10 plays a role in ovarian aging.*45 Animal studies have found that CoQ10 supports ovarian reserve, helps to reduce ovarian aging by restoring mitochondrial function, and increases embryo quality.*46,47 In humans, CoQ10 supplementation resulted in supporting healthy ovulation and helping to promote fetal health in 35 to 43-year-old women.*48,49
Another study found that CoQ10 supplementation improved assisted reproductive technology outcomes in young women.*50 CoQ10 made it easier to achieve a healthy ovarian response in young women with a low ovarian reserve.* CoQ10 was associated with an increased number of oocytes retrieved, a significant increase in fertilization rate and in the number of high-quality embryos.* In addition, there was a significantly lower rate of cancelled cycles due to no response to stimulation, less cancelled embryo transfers because of failed embryo development, and a larger number of cycles with cryopreserved embryos in the CoQ10 treated group than in controls.* Compared with controls, the clinical pregnancy and live birth rates were higher after CoQ10 supplementation, but this finding did not achieve significance, likely due to insufficient sample size.50
ALA is another mitochondrial rejuvenator.* ALA supports chromosomal health during oocyte aging by increasing energy for chromosomal activities.* A powerful antioxidant, ALA can quench reactive oxygen species in the mitochondria of oocytes and also can regenerate other antioxidant molecules.*51
From menstrual cycle irregularities and premenstrual concerns, to difficulty conceiving, to discomfort with menopause, a woman’s hormonal and metabolic health is critical to her quality of life. Women now have access to the most effective insulin-sensitizing dietary supplement available thanks to Inositol + Vitex Plus.* This innovative formula supports ovarian function and reproductive health with myo-inositol, CoQ10, and alpha-lipoic acid.* Myo-inositol and Vitex agnus castus help balance testosterone, menstrual cycle frequency, and assist in reducing mild, usual concerns of the menstrual cycle.* They are also helpful during and after menopause. ALA and chromium promote insulin sensitivity while defending from oxidative stress.* With Inositol + Vitex Plus, clinicians can now use the best of science and nature to optimize women’s hormonal, metabolic, and reproductive health.*
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