Relieve Constipation, Stress, and Poor Sleep via the Gut-Brain Axis

The gut-brain axis has been a scorching subject of dialog within the diet world, notably following a couple of landmark papers printed within the 2010s that explored the interactions between intestine microbiota and the central nervous system.[1-3]

For example, a lot of the physique’s serotonin is produced within the intestine – and by most, we imply mainly all of it. The intestine creates a whopping 95% of all of the serotonin used within the physique.[1]

This discovering could also be shocking at first, as serotonin is commonly thought-about primarily a mood-related neurotransmitter usually related to mind perform. Nonetheless, the perceived dichotomy between intestine and mind could also be deceptive.

The Shut Relationship Between the Intestine and the Mind

Intestine dysbiosis, a pathological imbalance of microorganisms within the intestine that influences serotonin synthesis, is believed to contribute to the event of main temper problems.[4] For higher or worse, intestine well being considerably impacts mind well being — and in a major manner.[5]

Serotonin, whereas categorised as a neurotransmitter, additionally has far-reaching results past the mind. Its receptors are extensively expressed all through the gastrointestinal tract, the place it regulates key digestive processes. This contains the contraction of easy muscle mass referred to as peristalsis, which coordinate the motion of meals by means of the digestive system.[6] It additionally influences the secretion of digestive enzymes and fluids, aiding within the breakdown and absorption of vitamins, supporting urge for food and digestion.[7]

Imbalances in serotonin ranges can result in numerous gastrointestinal problems, akin to irritable bowel syndrome (IBS), characterised by signs like stomach ache, bloating, and altered bowel habits.[6]

Because the scientific group higher understands the shut relationship between the intestine and the mind, we’re now seeing novel methods to enhance their functioning collectively utilizing diet and dietary dietary supplements. Immediately, we’re exploring one progressive strategy to bettering intestine well being — and it helps mind well being as nicely:

NXT’s Digexin – Easing Constipation By way of The Mind

Improved data of the gut-brain axis led to NXT USA’s creation of Digexin, a patented mix of ashwagandha root extract and okra root extract, distributed by Freemen Nutra. Ashwagandha is well-known to the dietary complement world, generally used as a mood-enhancing adaptogenic herb. Nonetheless, okra shouldn’t be as regularly mentioned.When you find out about Digexin, you’ll see what a superb mixture that is.

Digexin’s Improvement – Goal-Primarily based Complement Discovery

Usually, dietary supplements are evaluated for potential mechanisms of motion after their results are noticed. Nonetheless, Digexin was developed by means of a pharmaceutical strategy referred to as target-based discovery.

In target-based discovery, NXT recognized a well being illness (constipation) and a mechanism of motion (serotonin signaling) they wished to modulate, then sought compounds efficient for this particular mechanism and consequence.

So why did NXT need to goal serotonin particularly? The corporate observed that, although 40% of adults worldwide have a purposeful gastrointestinal dysfunction (FGID),[8] with 61% of Individuals reporting a major gastrointestinal symptom up to now week,[9] current options left a lot to be desired. In a phrase, NXT realized that they have been all mechanistic – they targeted on instantly stimulating peristalsis (laxatives), serving to type or loosen stools (psyllium husk fiber), or bettering intestine microbiome (probiotics).

Focusing on stress – a significant factor in intestine well being

Whereas soluble fibers like psyllium husk, which act as bulk-forming laxatives, may help many individuals with constipation, some people’ points are extra difficult than that. For example, one examine from 1997 discovered that 80% of sufferers with gradual transit (constipation) don’t reply to psyllium fiber supplementation.[10] Probiotics, then again, don’t actually goal constipation in any respect, as evinced by a 2023 trial which discovered no enhance in bowel motion frequency in comparison with placebo.[11] And chemical laxatives, whereas helpful for infrequent bouts of constipation, may cause dependence when used chronically.[12]

The group at NXT hypothesized that, to advertise steady bowel motion perform in the long run, an ingredient that helps temper and stress resilience can be wanted, since stressors are a significant factor within the onset and length of constipation.[13] For that objective, a serotonergic complement is an apparent alternative.

Candidate components by means of the method of elimination

NXT reviewed the scientific literature to search out botanicals with the potential to stimulate bowel actions through serotonergic signaling. After narrowing their listing down to fifteen candidates, the corporate performed preclinical exams on intestinal tissue utilizing a power meter. This enabled them to instantly measure the mechanical peristaltic power that every botanical stimulated ex vivo.

What they discovered was that two of their candidates – ashwagandha and okra – exhibited synergistic results. Basically, combining these two achieved the identical peristaltic impact as a better amount of both ingredient by itself.

Digexin’s Scientific Trials

Digexin has two wonderful gold commonplace human medical trials demonstrating its capability to enhance bowel perform — and assist temper and sleep within the course of:

Improves stress biomarkers and bowel perform (2024)

First, we’ll focus on a latest examine discovering that Digexin can successfully alleviate constipation, scale back stress, and enhance gastrointestinal perform, sleep high quality, and total wellness in adults — all with out hostile results.[14]

On this examine, 48 individuals aged 25 to 60 have been randomly assigned to obtain both

300 milligrams of Digexin,
500 milligrams of Digexin, or
an inert placebo

This examine aimed to quantify Digexin’s affect on constipation severity utilizing the next medical questionnaires:

Affected person Evaluation of Constipation-Signs (PAC-SYM)
Affected person Evaluation of Constipation-High quality of Life (PAC-QOL)
Gastrointestinal Symptom Score Scale (GSRS)
Full Spontaneous Bowel Actions (CSBM)

As with many well-designed preliminary research, this one additionally examined goal metrics for digestive well being and stress, together with serotonin blood ranges, inflammatory cytokines, the stress hormone cortisol, and gastrin (a hormone chargeable for triggering the secretion of abdomen acid).[14]

Supplementation with Digexin led to extremely statistically vital enhancements in topics’ PAC-QOL (Affected person Evaluation of Constipation-High quality of Life) scores.[14]

In research with massive knowledge tables, solely sure noticed results usually obtain statistical significance, which is why we generally spotlight people who do. Nonetheless, on this case, each single subscore on the PAC-QOL was considerably improved with Digexin administration! Moreover, all related p-values have been exceptionally small, at lower than 0.0001, indicating extraordinarily excessive statistical significance.[14] The commonly-accepted thresholds are 0.05, or much less generally, 0.025 – Digexin’s numbers are nicely beneath each of these!

Terribly vital outcomes

One other essential observe is that these results have been dose-dependent – the high-dose Digexin group skilled better advantages than the lower-dose one.[14]

What sort of impact sizes are we speaking about? Complete scores have been lowered by about 18% within the placebo group, however an astonishing 69% and 89% within the 300 milligram and 500 milligram Digexin teams, respectively.[14]

When it got here to the bodily discomfort rating – which is arguably crucial for constipation – the results have been much more pronounced. Whereas the placebo group skilled about an 18% discount, the high-dose Digexin group noticed a 93% enchancment![14] That’s an enormous impact measurement, not often seen in complement analysis or drug analysis. And once more, the p-value was just about zero, at lower than 0.0001.[14]

It’s onerous to overstate how spectacular these outcomes are.

Members who took Digexin confirmed vital enhancements on the PAC-SYM (Affected person Evaluation of Constipation-Signs) stock as nicely.[14]

Relating to the PAC-SYM, the scientists once more noticed huge, dose-dependent enhancements in all scores, with exceptionally low p-values.[14] The five hundred milligram Digexin group skilled a 94% enchancment in whole PAC-SYM rating.[14]

The identical degree of enhancements have been noticed for the GSRS, with vital enhancements seen in stomach ache, constipation, diarrhea, indigestion, and reflux.

Digexin additionally improved IL-6, IL-10, gastrin, serotonin, and cortisol ranges. All of those results achieved statistical significance within the high-dose (500 milligram) group.[14]

Amazingly, Digexin positively influenced stress biomarkers – IL-6 decreased, IL-10 elevated (which is useful since IL-10 is an anti-inflammatory cytokine), serotonin ranges elevated, and cortisol decreased. Furthermore, the elevation of gastrin within the Digexin teams additionally achieved statistical significance.

That is essential as a result of chronically excessive cortisol ranges are related to constipation-related GI problems like IBS.[14]

Alleviates purposeful constipation, reduces gastrointestinal transit time, and improves bowel perform (2024)

Nonetheless, that wasn’t the one examine printed in 2024 — Digexin additionally has a second randomized managed trial backing it.[15] This examine was related in design and construction to the earlier one, however used a a lot bigger pattern measurement – 135 individuals aged 25 to 60.[15] They have been additionally randomized to obtain both 300 or 500 milligrams of Digexin, or an inert placebo.[15]

Extra biomarker measured: gastrointestinal transit time (GIT)

The PAC-SYM, PAC-QOL, CSBM, and GSRS have been all utilized once more on this examine. Moreover, gastrointestinal transit time (GIT) was measured.[15] Identical to the earlier examine, this one measured cortisol, IL-6, IL-10, cortisol, gastrin, and serotonin, but additionally measured diamine oxidase (DAO) and zonulin.

Diamine oxidase (DAO) is an enzyme that degrades histamine within the intestine, stopping extreme histamine ranges. It breaks down histamine from meals and intestine micro organism, sustaining intestinal well being. A deficiency in DAO can result in histamine intolerance, inflicting signs like complications, gastrointestinal points, and allergic reactions.[16]

Zonulin is a protein that regulates the tight junctions between cells within the gastrointestinal lining.[17] Increased DAO helps discourage IBS, whereas decrease zonulin prevents the gastrointestinal tract from inflicting systemic, persistent irritation. Decrease zonulin ranges scale back intestinal permeability, stopping “leaky intestine”. This helps keep the integrity of the intestine barrier, stopping dangerous substances and pathogens from getting into the bloodstream. Decrease zonulin ranges are related to lowered irritation and a decrease threat of autoimmune and gastrointestinal problems.[17,18]

Equally phenomenal outcomes

Each doses of Digexin brought about statistically vital enhancements in all measured biomarkers of stress, irritation, and gastrointestinal integrity.[15]

This RCT discovered, similar to the preliminary examine, that Digexin administration brought about vital enhancements to the themes’ stress biomarkers. Most notably, cortisol was down 27% within the 300 milligram group and 43% within the 500 milligram group, whereas serotonin elevated by 26% and 29%, respectively.[15]

Digexin use led to vital enhancements within the GSRS (Gastrointestinal Symptom Score Scale) scores.[15]

Excessive-dose Digexin (500 milligrams) lowered the next GSRS scores:

Belly ache by 67%, vs 13% for placebo
Constipation by 74%, vs 21% for placebo
Diarrhea by 51%, vs 20% for placebo
Indigestion by 69%, vs 14% for placebo
Reflux by 65%, vs 19% for placebo

These results achieved statistical significance each intra-group and in comparison with placebo. Though the impact was dose-dependent, the 300 milligram dose brought about results nearly as massive as the five hundred milligram dose.

Full elimination of stomach ache signs!

As a observe for stomach ache, the bottom rating (aka absence of signs) within the GSRS is 1 — it doesn’t go to 0. So within the 500 milligram group, Digexin fully eradicated stomach ache signs. This was really the case within the 500mg group for all of the classes besides diarrhea!

Digexin considerably improved PAC-SYM (Affected person Evaluation of Constipation-Signs) scores,[15] similar to within the pilot examine.

Digexin additionally improved whole PAC-SYM scores by 93% within the low-dose group, and an astonishing 98% within the high-dose group.

Maybe most curiously, 500 milligrams of Digexin led to a 96% discount within the Worries and Concern rating on the PAC-QOL, indicating a particularly sturdy enchancment within the topics’ mind-set.[15] That is arguably the first consequence, as victims of constipation and different GI complaints need to really feel much less frightened about their situation. Since this impact was accompanied by sturdy enhancements in different stock scores and goal stress biomarkers, it may well’t be dismissed as mere placebo impact, both.

Digexin and sleep standing

When it got here to sleep, Digexin was additionally helpful. Curiously, the dose-response impact was not as impactful right here, however nonetheless very spectacular:

300 milligrams Digexin:

Awakening from sleep: 48.73% enchancment
Habits following wakefulness: 41.76% enchancment
Attending to sleep: 27.69% enchancment
High quality of sleep: 45.74% enchancment

500 mg Digexin:

Awakening from sleep: 49.42% enchancment
Habits following wakefulness: 40.71% enchancment
Attending to sleep: 37.37% enchancment
High quality of sleep: 50.38% enchancment

Bettering sleep high quality is essential, as sleep problems strongly correlate with GI problems like IBS.[19]

By day 60, Digexin supplementation considerably elevated diamine oxidase (DAO) ranges – by about 31% with 300 milligrams and 39% with 500 milligrams from baseline. Moreover, its use led to considerably lowered serum zonulin ranges by 5% with 300 milligrams and seven% with 500 milligrams from baseline. These adjustments have been vital in comparison with each baseline and placebo.[15]

Quickens gastrointestinal transit

Maybe crucial goal metric examined on this examine was gastrointestinal transit time (GIT), which refers back to the length it takes for meals to journey by means of the digestive tract. Extended transit time can result in constipation, as slower motion by means of the intestines causes elevated water absorption from the stool, making it tougher and harder to cross. In different phrases, a quicker GIT is healthier and may scale back the incidence of constipation.[15]

Therapy with Digexin considerably improved gastrointestinal transit time (GIT).[15]

Unsurprisingly at this level, Digexin lowered the gastrointestinal transit time by about 3 hours (13%) within the low-dose group and 4 hours (18%) within the high-dose group, in comparison with baseline.[15]

Once more, it’s onerous to overstate the outcomes of those two research.

Mechanisms of Motion: How Does Digexin Work So Nicely?

Most of our readers are aware of ashwagandha, which has in depth analysis supporting its capability to cut back stress and cortisol ranges,[20-23] resulting in quite a few downstream results.

Understanding the importance of the gut-brain axis, it’s unsurprising to see the way it additionally helps the intestine. Moreover, okra extract is totally new to most of our readers.

Let’s take a look at analysis for the 2:

Ashwagandha: Modulating Intestine Microbiota By way of Stress Response and Serotonin

Scientifically referred to as Withania somnifera, Ashwagandha is an evergreen shrub that’s lengthy been utilized in Ayurvedic medication for its stress-reducing, mood-enhancing results. Fashionable analysis is now starting to attach this to intestine well being:

In a preclinical trial, a withanolide-free Ashwagandha root extract was proven to modulate intestine microbiota,[24] probably influencing stress resistance and total intestine well being. The examine additionally means that the herb’s stress-protective elements may presumably be mediated by means of intestine microbiota regulation.

Also referred to as Withania somnifera, ashwagandha is the dietary complement business’s most distinguished adaptogenic herbs. Picture courtesy Wikimedia Commons.

A latest examine primarily focuses on Ashwagandha’s results capability to extend in serotonin ranges.[25] As mentioned on this article’s introduction, serotonin is essential for intestine well being because it regulates bowel actions and performs a job within the gut-brain axis. This implies potential dualistic advantages for GI tract perform by means of temper stabilization and stress discount.

Ashwagandha has adaptogenic properties,[26] which can assist intestine well being upkeep by regulating stress responses, lowering irritation, and probably balancing intestine microbiota.
Ashwagandha’s position in stress discount can not directly profit intestine well being, since persistent stress is thought to disrupt intestine microbiota and enhance GI tract points.[27]
Ashwagandha has an inhibitory impact on acetylcholine esterase, which can affect intestine motility.[28] By modulating acetylcholine ranges, the herb may affect the parasympathetic nervous system, positively affecting digestion and bowel actions.

Those that examine dietary dietary supplements possible aren’t shocked by these findings. Intestine well being is new space of analysis for ashwagandha, and we’re excited to see the way it progresses. Digexin’s launch appears to be nicely forward of the curve.

Extra attention-grabbing, nonetheless, is the utilization of okra:

Okra: Supporting Intestine-Mind Peptide Expression and Microbiota Variety

Okra is a flowering plant with edible inexperienced seed pods that originated in East Africa. It’s scientifically referred to as Abelmoschus esculentus, and is wealthy in polyphenols and polysaccharides which have been proven to have mood-improving results.[29,30] New analysis is taking scientific data even additional, exhibiting unbelievable results on brain-gut peptides in preclinical trials.[31]

Let’s stroll by means of the timeline of what we all know to date:

In 2014, researchers carried out a phytochemical evaluation on okra seed extracts, demonstrating its antioxidant, antistress, and nootropic actions.[32]

Is Okra extract the key weapon in Digexin? Trying on the analysis, it appears to be!

In 2018, one other group of researchers printed a examine specializing in the anti-fatigue exercise of okra’s polysaccharide fractions.[33] They hypothesized that it improved glycogen storage and lowered lactic acid accumulation. Additionally they performed a radical evaluation on the polysaccharides inside.

Shortly after in 2018, a examine was printed demonstrating the mood-improving exercise of an okra seed extract, specializing in its results on neurotransmitter ranges and oxidative stress markers within the mind.[29] It was seen that it may regulate neurotransmitter ranges (e.g., dopamine, serotonin, noradrenaline) and scale back oxidative stress.
An identical examine printed in 2019 confirmed that okra’s polysaccharides have mood-enhancing qualities, and have the flexibility to rebalance intestine microbiota.[30] It was in a position to do that by lowering irritation.
In 2020, a examine explored the results of okra powder on metabolic syndrome and intestine microbiota range in overweight mice.[34] The scientists discovered that okra powder supplementation led to improved intestine microbiota range, with elevated helpful micro organism and decreased dangerous micro organism. It additionally confirmed potential in lowering signs related to metabolic syndrome, akin to weight problems and irritation.
Most curiously, a 2021 examine illuminated the results of okra extract on brain-gut peptides and intestinal microbes in sleep-deprived rats, exhibiting that it enhanced expression of brain-gut peptides and ameliorated signs of sleep deprivation like anxiousness and cognitive impairment.[31]

It exhibits results on norepinephrine, serotonin, gastrin, CCK, and motilin,[31] which led to a number of the analysis on Digexin mentioned above.

Abstract on okra’s mechanisms of motion

General, we see the next results, all of which may assist gastrointestinal well being:

Antioxidant Exercise: Shield the intestine lining from oxidative stress.
Anti-inflammatory Properties: Scale back irritation within the intestine, selling a wholesome intestine surroundings.
Intestine Microbiota Modulation: Enhance the range and stability of intestine microbiota, enhancing digestion and nutrient absorption.
Mind-Intestine Axis Modulation: Influences brain-gut peptides, which play an important position within the communication between the intestine and mind, probably affecting temper and intestine motility.

We suspect that okra’s capability to cut back metabolic byproducts[33] can be a contributor to total intestine well being, and there’s much more potential with this plant that the dietary complement business is but to find.

Dietary supplements with Digexin

The primary Digexin-based complement in the marketplace is MiNDFUL Gi from Well being Through Diet (HTN). In every capsule, this method gives a mixture of 300 milligrams of Digexin with 100 milligrams of L-glutamine and a 1 billion CFU dose of lactobacillus acidophilus.

We love HTN’s consideration to element: Slightly than utilizing fillers in the remainder of the capsule, they selected to finish it with 100 milligrams of magnesium glycinate, which gives 10 milligrams (2% DV) of elemental magnesium. Whereas this isn’t a major quantity, we’re at all times supportive of utilizing each glycine and magnesium, particularly when it replaces different fillers.

However the important thing story is the 300 milligram dose of Digexin, which can be utilized as soon as day by day to yield lots of the advantages mentioned within the article above.

On the time of publication, it’s on pre-order, with an anticipated ship date of August 2024, however we’ll hold this space up to date with information and different Digexin launches.

Conclusion: Digexin is the Subsequent Main Intestine Well being Ingredient

The event of Digexin marks a major development in addressing constipation and total intestine well being by modulating the intricate relationship between serotonin signaling and gastrointestinal perform. NXT’s progressive strategy of target-based complement discovery has yielded a product that not solely enhances bowel actions but additionally improves stress resilience and temper, highlighting the profound connection between the intestine and the mind.

The 135-person medical trial demonstrates vital enhancements in nearly all conceivable gastrointestinal signs, stress biomarkers, and total high quality of life. It finds spectacular reductions in gastrointestinal transit time, together with enhancements in sleep high quality and lowered irritation, all of which place Digexin as a promising choice for these affected by constipation and associated problems.

This text was sponsored by Freemen Nutra, distributors of Digexin. Join PricePlow’s Freemen Nutra alerts beneath.

The complement business is at present seeing many worn-out product classes get revitalized by daring scientific R&D methods, and apparently, laxatives aren’t any exception. NXT’s recognition of the profound gut-brain, mind-body connection is poised to repay for the corporate in a major manner, and Freemen Nutra is the group to name if manufacturers and builders are able to pattern it for his or her subsequent intestine well being complement.

You’ll be able to join PricePlow’s Digexin and Freemen Nutra information alerts beneath, after which see our listing of articles discussing the ingredient, as we anticipate extra to return: