What is this ingredient? Vitamin B6, provided as pyridoxine HCl, is converted in the body to its active coenzyme form, pyridoxal‑5′‑phosphate (PLP). PLP is required for more than 100 enzymatic reactions, especially those involved in amino‑acid metabolism and the synthesis of key neurotransmitters such as serotonin, dopamine, and GABA [turn0search9]. Because of this, vitamin B6 status can influence mood, irritability, and fatigue—domains that are often affected in the premenstrual phase.

Several randomized, double‑blind trials have evaluated pyridoxine for premenstrual syndrome (PMS). A classic crossover trial using 50 mg/day pyridoxine over multiple cycles found that vitamin B6 significantly improved emotional‑type PMS symptoms such as depression, irritability, and tiredness compared with placebo [turn0search1]. A more recent treatment‑controlled trial (80 mg/day B6 vs. a broad micronutrient formula) reported medium effect‑size reductions in psychological and somatic PMS symptoms in both groups over three cycles, confirming that B6 alone can meaningfully reduce PMS severity in many women [turn0search0]. Other studies have also used B6 as a key ingredient in multi‑nutrient PMS formulas with good symptom relief [turn0search2][turn0search5][turn0search6].

Why include it in this formula? The “PMS Support - 60” product combines vitamin B6, vitamin B12, magnesium, lemon balm, black cohosh, diindolylmethane (DIM), chasteberry, and ashwagandha—clearly targeting mood, tension, and cycle‑related discomfort. Within this architecture, vitamin B6 is the central "neurotransmitter and symptom" pillar. By supplying PLP, it supports synthesis of serotonin and GABA (important for mood steadiness and relaxation) and dopamine (motivation and focus), which helps explain why trials have observed reductions in emotional and fatigue‑related PMS symptoms with 40–80 mg/day of pyridoxine [turn0search0][turn0search1][turn0search5][turn0search6][turn0search9].

B6 also participates in one‑carbon and homocysteine metabolism alongside B12 and folate (from diet), while magnesium contributes additional neuromuscular calming and lemon balm and ashwagandha provide botanical anxiolytic/adaptogenic support. Chasteberry and DIM focus more on hormone‑related aspects of the cycle. Together, these ingredients position vitamin B6 not as a sedative, but as a core biochemical support for the neurotransmitter balance that underlies mood, irritability, and energy swings around menstruation.

References

• [1] Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial
• [2] A Pilot Randomized Treatment‑Controlled Trial Comparing Vitamin B6 with Broad‑Spectrum Micronutrients for Premenstrual Syndrome
• [3] Effect of Combined Use of Calcium and Vitamin B6 on Premenstrual Syndrome Symptoms: a Randomized Clinical Trial
• [4] Femicomfort in the treatment of premenstrual syndromes: a double‑blind, randomized and placebo‑controlled trial
• [5] Vitamin B6: a molecule for human health?

What is this ingredient? Vitamin B12, here as methylcobalamin, is a water‑soluble B vitamin essential for one‑carbon metabolism, red blood cell formation, and normal nervous‑system function. In its coenzyme forms (methylcobalamin and adenosylcobalamin), B12 supports methionine synthase in the folate cycle and methylmalonyl‑CoA mutase in mitochondrial metabolism. These roles are critical for DNA synthesis, myelin maintenance, and balanced methylation reactions that influence neurotransmitter pathways and cellular energy.

B12 deficiency can lead to megaloblastic anemia and a range of neurologic and mood symptoms—fatigue, brain fog, low mood, paresthesias—even before full deficiency is clinically obvious. Correcting low B12 status normalizes homocysteine, restores hematologic parameters, and often improves energy and cognitive symptoms, making adequate B12 a foundational requirement for feeling mentally and physically steady throughout the month.

Why include it in this formula? “PMS Support - 60” combines vitamin B6, vitamin B12, magnesium, lemon balm, black cohosh root, diindolylmethane (DIM), chasteberry, and ashwagandha. Together, these ingredients target the two major dimensions of PMS: cyclical mood/energy shifts and hormone‑related physical symptoms. Within this framework, methylcobalamin is the "one‑carbon and energy" pillar. It works with B6 (and dietary folate) to support homocysteine–methionine balance and SAM‑dependent methylation, which underpin neurotransmitter synthesis and nervous‑system stability.

B12 also supports red blood cell production and oxygen delivery, helping reduce the background fatigue that can magnify premenstrual mood and pain. While B6, magnesium, lemon balm, and ashwagandha more directly modulate neurotransmitter tone and stress reactivity, methylcobalamin ensures that these systems have the basic genomic and hematologic support they need. In combination with DIM, chasteberry, and black cohosh—aimed at hormone‑cycle balance—vitamin B12 helps provide a more even metabolic and neurological baseline across the cycle, so PMS‑targeted botanicals can work on top of a well‑nourished foundation.

What is this ingredient? Magnesium, supplied here as magnesium oxide, is an essential mineral that participates in more than 300 enzyme‑catalyzed reactions. It is crucial for ATP production, neuromuscular signaling, and smooth‑muscle relaxation, as well as for the function of many enzymes involved in neurotransmitter synthesis and hormone action. In women, suboptimal magnesium intake is common and has been linked with mood changes, tension, and fluid‑related discomfort around the premenstrual period in observational and interventional work.

In a randomized, double‑blind, placebo‑controlled crossover study of women with mild premenstrual symptoms, 200 mg/day elemental magnesium as magnesium oxide for one cycle produced trends toward improvement in several PMS symptom clusters; importantly, when combined with vitamin B6, the same magnesium dose significantly reduced anxiety‑related premenstrual symptoms compared with placebo [7]. Earlier work from the same group also reported that magnesium supplementation alone improved premenstrual irritability and mood scores in affected women [1]. These data support a role for magnesium in easing neuromuscular tension and emotional lability across the cycle.

Why include it in this formula? “PMS Support - 60” combines vitamin B6, vitamin B12, magnesium, lemon balm, black cohosh root, diindolylmethane (DIM), chasteberry extract, and ashwagandha. Together, these ingredients target mood, stress, and hormone‑related symptoms around menstruation. Within this architecture, magnesium oxide is the "calming electrolyte" pillar. By supporting GABAergic and serotonergic enzyme systems, stabilizing nerve and muscle excitability, and contributing to vascular and smooth‑muscle relaxation, magnesium helps reduce cramping, tension, and anxiety‑type symptoms that often flare premenstrually.

The trial showing a synergistic reduction in anxiety‑related PMS symptoms when magnesium oxide (200 mg) was combined with 50 mg of vitamin B6 directly echoes this formula’s pairing of magnesium with a meaningful dose of B6 [7]. Lemon balm and ashwagandha add botanical anxiolytic and adaptogenic effects, while chasteberry and black cohosh focus on hormone‑cycle balance and DIM supports estrogen metabolism. In this context, magnesium oxide provides foundational neuromuscular and enzymatic support so that these hormone‑ and neurotransmitter‑modulating ingredients can act on a more stable, less “wired” physiological background.

References

• [1] Effects of a yeast-based magnesium preparation on premenstrual syndrome: a double-blind, placebo-controlled study
• [7] A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study

What is this ingredient? Lemon balm (Melissa officinalis) is a mint-family herb whose aerial parts (leaves and stems) are traditionally used as a calming, mood‑soothing remedy. The plant is rich in rosmarinic acid and other phenolic compounds that appear to modulate GABA and other neurotransmitter systems, giving it mild anxiolytic and sedative properties. Modern randomized, double‑blind, placebo‑controlled trials show that standardized lemon balm extracts can significantly reduce anxiety, stress, and depressive symptoms and improve overall mental well‑being and sleep quality in adults with emotional distress or poor sleep [0,1,5].

For example, a 3‑week RCT in 100 adults with moderate depression, anxiety, stress, or poor sleep found that 400 mg/day of a phospholipid‑based lemon balm extract significantly improved DASS‑42 depression, anxiety, and stress scores and Pittsburgh Sleep Quality Index scores, with no serious adverse events [1]. Other trials report reduced palpitations and lower anxiety in people with benign heart palpitations, and improved quality‑of‑life scores in postmenopausal women with sleep disturbance when lemon balm‑containing combinations were used [0,3].

Why include it in this formula? “PMS Support - 60” combines vitamin B6, vitamin B12, magnesium, lemon balm, black cohosh root, diindolylmethane (DIM), chasteberry fruit extract, and ashwagandha. The blend clearly targets the emotional, stress, and hormone‑related components of premenstrual syndrome. Within this architecture, lemon balm is the dedicated "calming and sleep‑support" herb. While B6, magnesium, and ashwagandha help regulate neurotransmitters and stress hormones, lemon balm offers fast‑acting support for anxiety, tension, and restless sleep—symptoms that commonly flare in the late luteal phase [1,5].

Its demonstrated ability to improve anxiety, depressive mood, and sleep quality over just a few weeks in stressed or symptomatic adults [1,5] makes it a useful complement to chasteberry and DIM, which act more slowly on cycle‑related hormones. In practical terms, lemon balm helps soften the emotional edges of PMS—irritability, nervousness, feeling “wound up” at night—so that the formula addresses both the underlying cycle biology and the day‑to‑day experience of mood and sleep around menstruation.

References

• [0] Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety
• [1] The possible "calming effect" of subchronic supplementation of a standardised phospholipid carrier-based Melissa officinalis extract in healthy adults with emotional distress and poor sleep conditions: a randomized, double‑blind, placebo‑controlled clinical trial
• [5] The effects of Melissa officinalis on depression and anxiety in type 2 diabetes patients with depression: a randomized double‑blinded placebo‑controlled clinical trial

What is this ingredient? Black cohosh (Actaea/Cimicifuga racemosa) root is a North American herb best known for use in menopausal symptom relief, especially hot flashes and mood‑related climacteric complaints. Standardized extracts contain triterpene glycosides and other constituents that do not behave like classic estrogens but do interact with central nervous‑system receptors. In vitro studies show that black cohosh extracts act as mixed competitive ligands and partial agonists at specific serotonin receptors (5‑HT1A, 5‑HT7) and at the human μ‑opioid receptor, supporting a neuromodulatory mechanism for vasomotor and mood symptoms rather than direct estrogen receptor agonism ([pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/12952416/?utm_source=openai)).

Randomized, double‑blind, placebo‑controlled trials using standardized black cohosh extracts in peri‑ and postmenopausal women report clinically relevant reductions in climacteric symptom scores and hot‑flash frequency over 8–12 weeks, with efficacy comparable to tibolone in some studies and good overall tolerability ([pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/25276716/?utm_source=openai)). Although these trials focus on menopausal rather than strictly premenstrual symptoms, they highlight black cohosh’s role in hormonally linked mood and vasomotor complaints.

Why include it in this formula? “PMS Support - 60” combines vitamin B6 and B12, magnesium, lemon balm, black cohosh root, diindolylmethane (DIM), chasteberry extract, and ashwagandha. Together, these ingredients clearly target the emotional, tension, and hormone‑cycle aspects of PMS. Within this architecture, black cohosh root functions as a "hormone‑linked vasomotor and mood" pillar. Its serotonergic and μ‑opioid receptor activity may help stabilize central temperature regulation and modulate mood and pain perception around the late luteal phase, much as it does for hot flashes and climacteric mood symptoms in menopausal women ([pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/12952416/?utm_source=openai)).

By acting at central neuromodulatory targets rather than as a direct estrogen mimic, black cohosh complements DIM and chasteberry—which work more on estrogen/progesterone balance—and magnesium, B6, lemon balm, and ashwagandha, which support neurotransmitter synthesis and stress resilience. In this context, black cohosh helps address PMS symptoms that overlap with perimenopausal complaints—such as breast tenderness, thermoregulatory shifts, and mood lability—contributing to a more comprehensive, multi‑pathway approach to monthly comfort.

What is this ingredient? Diindolylmethane (DIM) is a condensation product of indole‑3‑carbinol, the compound formed when glucosinolates in cruciferous vegetables (like broccoli and cabbage) are broken down. In the stomach, indole‑3‑carbinol dimerizes to form 3,3′‑diindolylmethane. DIM is best known for its effects on estrogen metabolism and cell‑cycle control. In human studies, DIM has been shown to shift estrogen metabolism toward greater 2‑hydroxylation—raising the urinary 2‑hydroxyestrone:16α‑hydroxyestrone (2/16α‑OHE1) ratio—an estrogen profile often considered more favorable in terms of proliferative signaling [11].

In breast and other hormone‑responsive cell models, DIM induces a G1 cell‑cycle arrest, reduces activity and expression of key cyclin‑dependent kinases (CDK1/2/4/6) and phosphatases such as Cdc25A, and increases the CDK inhibitor p21, leading to slowed proliferation and, at higher concentrations, apoptosis [1,2,3,8]. It also modulates estrogen‑receptor (ER) signaling and can act via ER‑dependent and independent pathways to alter growth‑factor and EMT‑related genes, including down‑regulating metastasis‑related CXCR4 in ER‑positive breast cancer models [5].

Why include it in this formula? “PMS Support - 60” combines vitamin B6, vitamin B12, magnesium, lemon balm, black cohosh root, DIM, chasteberry, and ashwagandha. The product is clearly designed to address mood, stress, and hormone‑cycle–related symptoms. Within this architecture, DIM is the key "estrogen‑metabolism and cell‑signaling" pillar. By favoring 2‑hydroxylation of estrogens and increasing the 2/16α‑OHE1 ratio in human pilot trials [11], DIM supports a less proliferative estrogen metabolite profile, which may be especially relevant for women who experience cycle‑sensitive breast tenderness or who are concerned about long‑term estrogen balance.

At the same time, DIM’s ability to induce G1 cell‑cycle arrest and modulate ER‑dependent gene expression in breast and endometrial cells [1,2,8,10] complements chasteberry’s effects on pituitary gonadotropins and black cohosh’s neuromodulatory impact on hormone‑linked symptoms. B6, magnesium, lemon balm, and ashwagandha focus more on neurotransmitters and stress responses, while DIM works upstream on how estrogens are processed and how their signals are interpreted at the cellular level. Together, they support a more balanced hormonal and emotional terrain across the menstrual cycle rather than acting as isolated symptom suppressors.

References

• [1] 3,3′‑Diindolylmethane (DIM) induces a G1 cell cycle arrest in human breast cancer cells that is accompanied by Sp1‑mediated activation of p21(WAF1/CIP1) expression
• [2] Induction of growth arrest and apoptosis in human breast cancer cells by 3,3′‑diindolylmethane is associated with induction and nuclear localization of p27(kip)
• [3] 3,3′‑Diindolylmethane inhibits breast cancer cell growth via miR‑21‑mediated Cdc25A degradation
• [5] Inhibitory effects of 3,3′‑diindolylmethane on epithelial‑mesenchymal transition induced by endocrine disrupting chemicals in breast cancer models
• [8] Bcl‑2 family‑mediated apoptotic effects of 3,3′‑diindolylmethane in human breast cancer cells
• [11] 3,3′‑diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study

What is this ingredient? Chasteberry (Vitex agnus‑castus) fruit extract is obtained from the berries of the chaste tree, a Mediterranean shrub long used for menstrual and premenstrual complaints. Standardized extracts contain diterpenes (such as agnusides) and other constituents that act primarily on the pituitary, modulating prolactin and, secondarily, luteinizing hormone. Pharmacologic and clinical data indicate that chasteberry can normalize latent hyperprolactinemia and thereby ease symptoms like breast tenderness and cyclical mastalgia [turn0search9].

Randomized, double‑blind, placebo‑controlled trials in women with premenstrual syndrome have shown that Vitex agnus‑castus fruit extract significantly reduces typical PMS symptoms—including irritability, mood swings, headache, breast fullness/tenderness, and bloating—compared with placebo over three cycles [turn0search1][turn0search3]. A meta‑analysis of properly characterized chasteberry preparations concluded that these extracts are more effective than placebo for global PMS symptom relief, with good tolerability [turn0search4]. Chasteberry has also demonstrated efficacy in reducing cyclical mastalgia in controlled trials [turn0search0][turn0search5].

Why include it in this formula? “PMS Support - 60” combines vitamin B6, vitamin B12, magnesium, lemon balm, black cohosh root, diindolylmethane (DIM), chasteberry fruit extract, and ashwagandha. Together, these ingredients target emotional, somatic, and hormone‑cycle symptoms around menstruation. Within this architecture, chasteberry is the primary "pituitary–prolactin and breast" pillar. By gently lowering elevated prolactin responses and rebalancing luteal‑phase pituitary signals, it directly addresses breast tenderness, fluid retention, and many core PMS symptoms documented in clinical scales [turn0search1][turn0search3][turn0search9].

Chasteberry’s hormone‑modulating actions complement DIM’s support for estrogen metabolism, black cohosh’s neuromodulatory role in hormone‑linked discomfort, and the calming effects of magnesium, lemon balm, B6, and ashwagandha on mood and stress. In combination, these ingredients help create a more even hormonal terrain and a calmer nervous system across the menstrual cycle, so both physical (breast tenderness, bloating) and emotional (irritability, tension) aspects of PMS are addressed in a coordinated way rather than piecemeal.

References

• [1] Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo‑controlled study
• [2] Evaluating therapeutic effect in symptoms of moderate‑to‑severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women
• [3] Vitex agnus‑castus in premenstrual syndrome: A meta‑analysis of double‑blind randomised controlled trials
• [4] Effects of Vitex agnus and flaxseed on cyclic mastalgia: a randomized controlled trial
• [5] Chaste tree (Vitex agnus‑castus)—pharmacology and clinical indications

What is this ingredient? Ashwagandha (Withania somnifera) is a traditional Ayurvedic adaptogen used to help the body cope with physical and emotional stress. A 4:1 whole‑plant extract concentrates bioactive withanolides and related compounds from roots and aerial parts. Modern randomized, double‑blind, placebo‑controlled trials consistently show that standardized ashwagandha extracts reduce perceived stress and anxiety and improve sleep and mood in adults with high baseline stress or insomnia [0,1,4,5,7]. Doses in the 240–600 mg/day range have produced significant reductions in Perceived Stress Scale and Hamilton Anxiety scores, along with lower serum cortisol and better sleep quality, compared with placebo [1,4,5,7].

Recent work also demonstrates benefits for cognition, executive function, and mental fatigue in adults with self‑reported cognitive and energy problems, and confirms good safety and tolerability over 8–12 weeks in healthy volunteers [2,6]. Altogether, ashwagandha is best characterized as a non‑sedating adaptogen that smooths the body’s stress response and supports calmer, more stable energy.

Why include it in this formula? “PMS Support - 60” combines vitamin B6 and B12, magnesium, lemon balm, black cohosh, diindolylmethane (DIM), chasteberry, and ashwagandha. The product clearly targets both the hormonal and emotional sides of premenstrual syndrome—mood swings, anxiety, irritability, fatigue, and sleep disruption. Within this architecture, ashwagandha is the primary "stress‑resilience and all‑cycle energy" pillar. By lowering perceived stress and anxiety and improving sleep and vigor in randomized trials [0,1,4,5,7], it helps buffer the HPA‑axis overreactions that can make PMS symptoms feel overwhelming.

Ashwagandha complements magnesium and vitamin B6, which support neurotransmitter balance, and lemon balm, which offers more immediate calming and sleep benefits. Meanwhile, chasteberry, DIM, and black cohosh focus upstream on hormone‑cycle and estrogen‑metabolism balance. Used together, ashwagandha helps ensure that as hormones naturally rise and fall across the month, the stress system and mood response remain steadier—so emotional and fatigue‑related PMS symptoms are less intense and more manageable.

References

• [0] A double‑blind, placebo‑controlled evaluation of the anxiolytic efficacy of an ethanolic extract of Withania somnifera
• [1] Adaptogenic and anxiolytic effects of Ashwagandha root extract in healthy adults: a double‑blind, randomized, placebo‑controlled clinical study
• [2] Safety and efficacy of Ashwagandha root extract on cognition, energy and mood problems in adults: prospective, randomized, placebo‑controlled study
• [4] An investigation into the stress‑relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: a randomized, double‑blind, placebo‑controlled study
• [5] Efficacy and safety of Ashwagandha root extract in insomnia and anxiety: a double‑blind, randomized, placebo‑controlled study
• [6] Safety of Ashwagandha root extract: a randomized, placebo‑controlled study in healthy volunteers
• [7] A new Ashwagandha formulation alleviates stress and anxiety symptoms while improving mood and sleep quality: a randomized, double‑blind, placebo‑controlled clinical study