Silicon dioxide [common in supps] worsens neurogenesis in hippocampus. causes impairment in offspring. +Grape Seed Procyanidins Extract benefits

[cs3000]

The smaller nanoparticles specifically are dangerous. and no way of telling what you're getting with the silicon dioxide often found in supplements
Maternal exposure to silicon dioxide nanoparticles reduces hippocampal neurogenesis and synaptogenesis and induces neurodegeneration in rat offspring hippocampus

wasnt a crazy dose either. 250mg - 300mg human equivalent , orally

Silicon dioxide nanoparticles (SiO2-NPs) are among the most widely used nanoparticles because of their chemical-physical properties. Since most brain maturation occurs in the neonatal period in humans and many mammals, it is important to understand how NPs may affect this process. This study tested the hypothesis that SiO2-NPs from treated dams could affect the hippocampus of neonatal rats during lactation.
Twenty-four pregnant rats, after delivery, were divided into three groups of control, SiO2-NPs (25 mg/kg) and SiO2-NPs (100 mg/kg). The rats were treated from 2nd to 21st days post-delivery by gavage and the effects of these NPs were evaluated in the offspring’s hippocampi to reveal the effects of maternal exposure to SiO2-NPs during lactation on the offspring’s hippocampi.
The offspring in the SiO2-NPs groups had higher malondialdehyde concentration and lower antioxidant activity in the hippocampi than the non-treated control group. The mean number of doublecortin positive (DCX+) cells and synaptophysin expression in the hippocampi of the SiO2-NPs groups were significantly lower than the control group, whereas the mean number of dark neurons was significantly higher. Also, animals in the SiO2-NPs groups had a weak cognitive performance in adulthood. In conclusion, maternal exposure to SiO2-NPs via breastfeeding could affect offspring’s hippocampal neurogenesis and synaptogenesis, leading to impaired cognitive performance.

This is likely 1 reason why some people feel worse on a bunch of supplements that are supposed to be having benefits
(silicon dioxide is found in a lot of them), and especially if they don't have sufficient oxidative stress protection

DCX+ neuronal precursor cells are like stem cells for the brain.
increased expression means they are actively replicating and maturing into more neurons (more neurogenesis is happening)

Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects

^ in humans they used silica dioxide as a "placebo", which reduced blood BDNF by 34%

Quite unexpectedly, treatment with placebo (silica dioxide) resulted in a 34 % reduction in BDNF blood levels (P¼0·09

Low neurogenesis in the hippocampus is linked to depression & poor cognition
----

For restoring hippocampus neurogenesis i like grape seed proanthocyanidin extract, shown to have a profound effect on cognition in aged mice and >2x increase in hippocampal DCX+ cells.
In the study above they used 100mg of GSE which improved blood BDNF levels in humans. not as much as coffeeberry , because of the extract type. They used GSE high in polyphenols but not standardized to high as **** proanthocyanidins

There's a big difference between GSE and GSPE (grape seed proanthocyanidin extract). GSPE is almost all procyanidins. so with GSE you'd need a much higher dose, and get other stuff you might not want idk
procyanidins are one of the most potent compounds for increasing BDNF / neurogenesis

https://www.researchgate.net/publication/351486159_Grape_seed_extract_effects_on_hippocampal_neurogenesis_synaptogenesis_and_dark_neurons_production_in_old_mice_Can_this_extract_improve_learning_and_memory_in_aged_animals

It has a big impact on increasing exercise time to exhaustion - ~250mg-300mg human dose extended from 8.6 minutes to 13 minutes (+50% improvement). 500mg increased to 16.63 minutes
.lowered lactic acid 12.44 -> 9.51
.raised oxidative stress protection enzymes, lowered MDA (250mg is close to 500mg dose effects)
.slight anti-inflammatory effect (mild not major, but should also benefit immunity so its a bonus)
. improved 2 mitochondria function markers in muscle +20% (ATPase and Succinate DH SDH)

even small doses have some effect

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis protects lymphocytes (& mitochondria)
and actually induced TH1 Grape Seed Extract Activates Th1 Cells In Vitro so should boost immunity [this is the procyanodins rich extract]

The reason why red wine has some benefits associated vs other alcohols is because it has these procyanidins. usually alcohol damages immunity. but red wine in reasonable amounts (360ml) protects against the immune damaging effects , and increases NK cell ratio.
small study size but should be legit

Wine Modifies the Effects of Alcohol on Immune Cells of Mice

Ethanol may be detrimental to immune cells due to the generation of free radicals during detoxification. If this is true, then alcoholic beverages tha…

www.sciencedirect.com

GSPE also helps mitochondria function (if timed right) which is the basis for cellular energy

better mitochonrial effect administered in night time in rats (so day time for humans? when more metabolically active). . Time-of-Day Circadian Modulation of Grape-Seed Procyanidin Extract (GSPE) in Hepatic Mitochondrial Dynamics in Cafeteria-Diet-Induced Obese Rats probs will go with <12pm. Rats are nocturnal , so during their wake phase (night time) mitochondrial fusion genes go to 1.5x to 2x expression with GSPE instead of when taken during their sleep phase (day time). https://www.mdpi.com/nutrients/nutr...eploy/html/images/nutrients-14-00774-g004.png
*250mg - 500mg is a good dose.

The most remarkable result is that there is a clear overexpression in both Mnf1 and Mfn2, a 27 and 65% increment, respectively, in the GSPE group in the night treatment (ZT12) compared with the CAF-VH group. Altogether, these results could suggest that the effect of GSPE inducing the fusion of mitochondria seems to be more relevant with night treatment and shortly after GSPE ingestion (ZT1) in cafeteria-fed animals Altogether, these results could suggest that the effect of GSPE inducing the fusion of mitochondria seems to be more relevant with night treatment and shortly after GSPE ingestion (ZT1) in cafeteria-fed animals
Regarding the GSPE effect, a decrease of almost 30 percent in Fis1 gene expression is observed in the ZT13 condition. As some of these effects were also observed for the fusion genes, it seems that morning GSPE treatment promotes a relatively mild effect and prompts an equilibrium between the fusion and fission events, suggesting that there could be a balance in the morphology of the mitochondrial population.
In consequence, it seems that in the night treatment, mitochondria could be more present in an elongated/fussed form due to both the induction of fusion genes and the inhibition of fission genes induced by GSPE.
Interestingly, we observed that as expression of Fis1 and/or Drp1 in CAF-VH group decreases, concentrations of TCA metabolites increase at the same time of death.<-- but they noticed increase in TCA cycle metabolites during AM administration of GSPE , why if this was creating more fission?
In this sense, our results show that circadian oscillations of Rorα and Bmal1 were disrupted in the CAF-diet group and that GSPE was able to restore this disruption of both clock genes when treated at night restores circadian rhythm?
increase in the expression of mitochondrial fission genes, can result in fragmented mitochondria that are susceptible to apoptosis
Notably, the major improvements in GSPE supplementations were seen at the ZT12 dosage (12 hours after dosing). This may be partially explained by the fact that GSPE enhances the energy profile of rats and improves mitochondrial function and oxidation in the liver at night, during the active phase when rats are metabolically more active, as rats are nocturnal animals

helps restore complex i and ii activity a little, by 7 hrs after taking


GSPE induces cell death in leukemia cells without harming normal cells


Protects against oxidative stress with multiple x more potency than Vit C or Vit E. shown protective against toxic metals with cadmium study. The protective effect of grape seed procyanidin extract against cadmium-induced renal oxidative damage in mice - PubMed

restorative in diabetes https://www.researchgate.net/public...turbances_of_Red_Blood_Cells_in_Diabetic_Rats

------ possible downsides ------
.Some concerns is potential to inhibit cholesterol synthesis , and fat digestion by inhibiting fat digesting enzymes and binding in intestine Inhibitory effects of grape seed extract on lipases . havent looked into doses in vivo for this yet.

.i would take it away from iron foods unless trying to decrease iron, due to the binding & less absorption


.Inhibiting MAO-A too much = skew towards much higher serotonin. in rats this leads to a more fearful character with increased aggressiveness. some toxic things like cadmium causes MAO-A inhibition. & the spice pepper etc

Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAOA MAO-A lowering from normal lvls -> more fearful & more aggressive. 9x more serotonin and 2x more norepinephrine (mao-a inhibition is way more serotonergic)

A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males

GSPE (procyanidins) inhibits MAO-A in the brain BUT also MAO-B with similar potency, and the effect is mild ~15% at a 250mg-300mg dose

nice study on neurotransmitter effects of GSPE (just the procyanidins) in different brain regions https://kd.nsfc.gov.cn/paperDownload/1000001091895.pdf
there's a dose dependent effect on raising brain serotonin, norepinephrine and dopamine. may be best to stick to 250mg human dose . i saw another less detailed study where 2gram amounts raised whole brain serotonin more than dopamine, slightly higher than baseline, and tanked noradrenaline (did not inhibit acetylcholinesterase which is a positive for many tho).
so no need for gram amounts. in lower active doses dopamine is raised more. by 7 days

frontal cortex: serotonin 515 -> 628 [+20%]
dopamine 17.4 -> 29.3 [+70%]
both metabolites lower

hippocampus: serotonin 615 -> 708 [+15%]
dopamine: 23.6 -> 36.1 [+50%]

hypothalamus: serotonin 424 -> 549 [+30%]
dopamine 16.1 -> 20.9 [+30%}

So while it does raise serotonin, it raises dopamine more. and noradrenaline also rises.

green coffee extract doesnt have procyandins or enough of them. coffeeberry / fruit does with the right extract (not the caffeine one it should be like 1% caffeine). but GSPE is 95% procyanidins.

BDNF brain cell generation benefits should hit in low doses. the ~30% blood BDNF increase in humans was from 100mg of GSE (low in procyanidins) ~150mg also worked here Grape seed extract enhances neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice - PubMed but not sure on the extent. so even lower doses of GSPE should have effect,

Vitamin D also increases neurogenesis in hippocampus Anti-apoptotic and neurogenic properties in the hippocampus as possible mechanisms for learning and memory improving impacts of vitamin D in hypothyroid rats during the growth period - PubMed

GSE increases intracellular ATP production Grape skin extract modulates neuronal stem cell proliferation and improves spatial learning in senescence-accelerated prone 8 mice

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want to find out how significant the cholesterol esterase inhibition & bile acid binding is at what doses (cholesterol is protective & needed)
can we assume GSPE dose is 5x equivalent of GSE?

https://www.researchgate.net/public..._vinifera_L_and_its_antihyperlidemic_activity
^ 1g human dose equivalent of GSE (not GSPE) inhibited cholesterol acutely ~5% in rats fed high fat diet. <_250mg GSPE may be insignificant?

 

[Candeias]

It also has strong antifungal, antimicrobial and antiviral action. But from what I've read only 5-10% are absorbed in the digestive tract.. would a liposomal product be better?

 

[cs3000]

tried ~200mg and acutely gave a negative change in state , felt similar to when i tried a decent dose of pepper (mao inhibition, poor cognition negative thinking). also could be iron lowering or lowering estrogen being typically low, or it takes up to 7 days for dopamine to outmatch the serotonin
so im sticking to lower doses for now , which should work also for BDNF


this shows it does inhibit aetylcholinesterase 25% at 320mg
Procyanidins extracted from the lotus seedpod ameliorate scopolamine-induced memory impairment in mice - PubMed this one Combination of Procyanidins Extracted from Lotus Seedpod and <i>N</i>-acetyl Cysteine Ameliorates Scopolamine-induced Memory Impairment in Mice combo with scopolamine reduced the elevated AchE back to control -> 60mg/kg 320mg AchE - 0.58-> 0.44 (25%)


has effect in lower doses
mice - 10mg/kg 20mg/kg has effects , is protective against cisplatin cancer treatment

Grape-Seed-Derived Procyanidin Attenuates Chemotherapy-Induced Cognitive Impairment by Suppressing MMP-9 Activity and Related Blood–Brain-Barrier Damage

(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been...

www.mdpi.com

so ~50mg - 100mg.
it protects blood brain barrier integrity great
good significance at ~100mg but barely mild ~50mg , ~100mg is lower effect but similar to 200mg

by the mice brain study 60mg didnt impact neurotransmitters in the 3 brain regions


microdoses may work for BDNF? http://www.veterinaryworld.org/Vol.16/February-2023/17.pdf
in this they used the microgram symbol twice , but later said mg? was it micrograms or miligrams combined with vitamin C red grape extract 95% flavanols rats 2.5mg human (or 2.5g if not micrograms/kg)dose 4 weeks BDNF in brain tissue 2x with no ache inhibition

In the exercise study it did start working even at very small doses of 1mg/kg aka 5mg-6mg human,
reducing lactic acid starting to boost oxidative stress protection enzymes and boosted exercise performance

Human BDNF study showed 100mg coffeeberry boosted peripheral BDNF more than double , and this was not standardized to
procyanidins (which they mentioned was the responsible compound as isolated chlorogenic acid did not have effect)
so that would have been a much lower amount than what's found in 100mg standardized to 95%.
meaning 50mg should even be potent enough for a great BDNF boost based on this


--

the procyanidins specifically are extremely potent anti-estrogen compounds, with a Ki value of 6.
(good for inhibiting estrogen cancer growth, but if low estrogen have the potential to crash it)

Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds - PubMed

In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast...

pubmed.ncbi.nlm.nih.gov

nice study

These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.

Compounds found in HPLC peaks 1–6 and 8 had similar UV absorbance characteristics to procyanidins B1 and B2 and to catechin and epicatechin standards. The aromatase activity results show that all HPLC fractionated compounds inhibited aromatase in a dose-dependent manner (Fig. 1). The most effective inhibition curve was observed with HPLC peak 1
HPLC peak 1 exhibited a mass (M+) of 579 and an elemental formula of C30H27O12, which confirmed that HPLC peak 1 is a procyanidin B dimer.


Our in vitro studies have found that most of the chemicals in the 60–80% methanol-eluted polyamide fraction are procyanidin B dimers. These compounds have been shown to be inhibitors of aromatase.
in vivo... These cells proliferate in an androgen-dependent manner. It was found that mice fed daily with the polyamide 70M at 50- and 100-μl doses had a significant reduction in tumor growth when compared with the control. The average tumor weights for each group were as follows: 58.5 ± 23.2 (control), 44.8 ± 30.5 (70M wine extract, 25 μl), 36.4 ± 25.9 (70M wine extract, 50 μl), and 33.3 ± 26.8 mg (70M wine extract, 100 μl).
the ovary-uterine weights of mice fed daily with the polyamide 70M at 50 and 100 μl were significantly smaller than the weights of the control mice.
Serum from each mouse was also collected and analyzed for estradiol and estrone concentrations. Mice treated with increasing concentrations of wine extract showed a decreasing trend in the levels of estradiol and estrone compared with the control.
The results from uterine weight measurements and circulating estrogen levels support the hypothesis that in situ-produced estrogen plays a larger role in aromatase expressing and ER-positive breast tumor growth than circulating estrogen.

The most active procyanidin B dimer was found to inhibit aromatase with a Ki value of 6 μm, and the preparation of procyanidin B dimer mixture was found to be much more potent than any one of the individual procyanidin B dimers

(there's a study measuring estrogen levels after gse in women which didn't show an effect - but they used GSE , the procyanidins are the important part.)

equivalent to 125ml of red wine a day , inhibits estrogen (bump it up to 200ml to account for regional differences, should = ~40mg procyanidins daily )

Therefore, consumption of 125 ml of red wine/day would provide adequate amounts of procyanidin B dimers to suppress in situ aromatase in an average postmenopausal woman

It also has strong antifungal, antimicrobial and antiviral action. But from what I've read only 5-10% are absorbed in the digestive tract.. would a liposomal product be better?

not sure , but the supplement doses are bioavailable enough for effects

 

[cs3000]

has effect in lower doses
mice - 10mg/kg 20mg/kg has effects , is protective against cisplatin cancer treatment

Grape-Seed-Derived Procyanidin Attenuates Chemotherapy-Induced Cognitive Impairment by Suppressing MMP-9 Activity and Related Blood–Brain-Barrier Damage

(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been...

www.mdpi.com

so ~50mg - 100mg.
it protects blood brain barrier integrity great
good significance at ~100mg but barely mild ~50mg , ~100mg is lower effect but similar to 200mg

by the mice brain study 60mg didnt impact neurotransmitters in the 3 brain regions


microdoses may work for BDNF? http://www.veterinaryworld.org/Vol.16/February-2023/17.pdf
in this they used the microgram symbol twice , but later said mg? was it micrograms or miligrams combined with vitamin C red grape extract 95% flavanols rats 2.5mg human (or 2.5g if not micrograms/kg)dose 4 weeks BDNF in brain tissue 2x with no ache inhibition

In the exercise study it did start working even at very small doses of 1mg/kg aka 5mg-6mg human,
reducing lactic acid starting to boost oxidative stress protection enzymes and boosted exercise performance

Human BDNF study showed 100mg coffeeberry boosted peripheral BDNF more than double , and this was not standardized to
procyanidins (which they mentioned was the responsible compound as isolated chlorogenic acid did not have effect)
so that would have been a much lower amount than what's found in 100mg standardized to 95%.
meaning 50mg should even be potent enough for a great BDNF boost based on this

^
some further insight here

Authentication error - ProQuest

Explore millions of resources from scholarly journals, books, newspapers, videos and more, on the ProQuest Platform.

www.proquest.com

Both red wine phenolic extracts present high purity in polyphenols (> 91%; w/w) but TPx-MT2 contains more anthocyanins than TPx-MT7 (14.00% w/w versus 8.43% w/w) while TPx-MT7 contains more proanthocyanidins than TPx-MT2 (6.17% w/w versus 4.61% w/w)

So their MT2 extract = 18.61% combined anthocyanins + procyanidins, 4.61% pro
MT7 extract = 14.6% combined, 6.17% pro

*both restored sucrose preference and immobility time in chronic stress (chronic cortisol), 20mg/kg in mice
MT7 worked better than MT2, implying the procyanidins content was the main effect (otherwise MT2 with a higher combined % would have showed same if not better effect)

so ~100mg human dose of their extract, at 6.17% procyanidins (bump it up to 10% for the fuq of it)

= 10mg procyandins to restore BDNF to normal and give antidepressant effect
(much more than the relative megadoses found in supplements)

when they inhibited TrkB (BDNF receptor) the antidepressant effect went away
restored BDNF to (but not past) control levels, in the hippocampus. cortex results didnt reach statistical significance

Although both red wine phenolic extracts showed their potent reversing the anhedonia effects in the depressed mouse model, TPx-MT7 containing more proanthocyanidins appeared more effective on the antidepressant-like activity than TPx-MT2 containing more anthocyanins, indicating that proanthocyanidins would have a greater antidepressant-like effect than anthocyanins. The antidepressant-like effects may be speculated to be mediated by its modulatory action on the HPA axis function and its ability to prevent the alterations of BDNF, pTrkB/TrkB and pCREB/CREB levels in the hippocampus and prefrontal cortex of depressed mice

(also sticking to lower end may avoid significant T cell immunity lowering, seen at >250mg? <--- these doses may be better suited for reducing cytokines during inflammatory stage, rather than in infection elimination stage
tho the oligomeric procyanidins do have direct anti-viral effects e.g agaisnt Dengue virus Oligomeric procyanidins stimulate innate antiviral immunity in dengue virus infected human PBMCs and blocking HSV ability to infect cells Inhibition of herpes simplex type 1 and type 2 infections by Oximacro®, a cranberry extract with a high content of A-type proanthocyanidins (PACs-A)
studies mixed Oligomeric Procyanidins Interfere with Glycolysis of Activated T Cells. A Novel Mechanism for Inhibition of T Cell Function VS Grape Seed Extract Activates Th1 Cells In Vitro [in vitro powers up T cells but reduces counts?]
& protective effect against immune suppression from alcohol in red wine study in vivo - did not reduce lymphocyte "response" to LPS at ~70mg human equiv -
after LPS with water drinking mice NK cells go up to 40%, with the procyanidins NK cell response was 60%. lymphocyte % and NK cell % also go up vs water without the LPS challenge. but they dont mention counts.

 

[cs3000]

(one downside is it gave me insane gas , but my gut is in bad shape (its supposed to have benefits on reducing endotoxin effects & restoring permeability so Beneficial Effects of Proanthocyanidins on Intestinal Permeability and Its Relationship with Inflammation) -
but even low dose increases the amount of Akkermansia bacteria https://www.tandfonline.com/doi/full/10.1080/10408398.2022.2105802

Akkermansia is part of a healthy gut , it degrades mucin to produce short chain fatty acids which are beneficial for gut energy (which is why mucin goes up with grape seed extract as a response)
but the problem is it produces sulfur in the process. so if u have a high amount of sulfur reducing bacteria , that will turn into too much hydrogen sulfide, and good luck breathing when that comes out. useful if you want to assassinate someone in an office. healthy gut may not get a noticeable response idk)