Acai, Quercetin, and Ashwagandha promote Nrf2. Do Not Overdose!

[park_bear]

Acai has received a positive report, in a study using a mouse model of Parkinson's: Açai Berry Mitigates Parkinson’s Disease Progression Showing Dopaminergic Neuroprotection via Nrf2 HO1 Pathways link.springer.com/content/p...

In this study, treatment with açai berry was started 24 hours after administration of the toxicant. I would prefer a longer wait but most studies wrongly apply the treatment prior to the toxicant so we have to take what we can get. This was previously reported favorably on this site: healthunlocked.com/cure-par...

Nrf2 is a transcription factor, meaning it affects the transcription of a gene in the cell nucleus. pubmed.ncbi.nlm.nih.gov/234... "Nrf2 is the master regulator of inducible antioxidant responses, that can attenuate cellular injury from oxidative stress"

Here is a study which compares açai to quercetin, ashwagandha and other compounds as inducers of Nrf2: ncbi.nlm.nih.gov/pmc/articl...

They found açai was an inducer of Nrf2, although not as powerful as quercetin and ashwagandha (figures 3 and 4). Quercetin is about 2.5 times stronger and ashwagandha 7 times stronger. This was a cell culture model, so it did not include any differences in absorption or passage through blood-brain barrier. To the extent that the effectiveness of açai is due to its induction of Nrf2 this is likely all the more so for quercetin and ashwagandha.

Albert Wright (wriga) has done considerable work on using sulfurophane from broccoli seed to induce Nrf2. As he explained here: healthunlocked.com/cure-par...

"So what happens if you continue to boost Nrf2? You will eventually reach saturation and get a rebound effect due to the negative feedback loops which include Bach1. The virtuous circle then turns back into a vicious circle and you start a downward path. This is where dosing becomes critical. Less is better once you start the process. It's a tricky route to follow and it took me a while to find it." Based on my recent experience this also applies to taking acai.

Per the study cited at top, the human equivalent dosage of açai is about 3 grams after applying the appropriate animal to human adjustment. I took about 5 grams of a freeze-dried product – a heaping teaspoonful – daily, mixed in with my breakfast porridge after it cooled. I took it for about 2 1/2 weeks, during which time I experienced a slow deterioration – worse motor impairment. There was a confounding factor because during this time the need to take other things arose in order to treat an unrelated condition. Be that as it may, after I stopped taking the acai, over a few days my motor impairment improved to what it had been prior to starting. To double check on this I once again took a single dose in the morning a week ago. I did not give the matter any further thought at that time and went about my business. The result was awful – after a few hours my motor impairment was so bad I was physically unable to do my hike. First time that ever happened due to the motor impairment. After one week I am at least recovered enough to be able to resume hiking.

My mistake? 5 grams instead of 3 grams was only a small part of the problem. The big mistake was not accounting for the fact that the study used whole berries while I was using freeze-dried product. According to this reference: harmonyhousefoods.com/asset...

Rehydrating freeze-dried berries increases the weight by factor of 4. So the equivalent to 3 grams of fresh or frozen berries would be about .75 grams freeze-dried product. So I was taking more than 6 times the equivalent mouse dosage. If this were any other sort of edible berry it would not have made any difference, but that was not the case.

I did not experience any effect from my trials of quercetin, but in that case I used a fraction of the açai dosage – after all, they were capsules and not berries. Plus there are unknowns as to comparative absorption and passage through the blood-brain barrier.

I cannot recommend açai, however, if you choose to try it I strongly recommend keeping your dosage down to .75 gram, or less, of freeze-dried product daily. Also, if you choose to try it, an appropriate scale for weighing out gram quantities is a necessity.

[Smokeypurple]

Thank you for this reminder PB.

We tend to think such things can't have negative effects. I did a similar thing a couple of years ago by misreading a post of yours about cinnamon. I lavishly added it to my porridge for days in a row and was very worse for wear for a week. I then realised that you had been very specific on quantity and even warned of your own 'overdose' reaction but I had read without my usual rigour as it's just a cake ingredient, right? Wrong.

[park_bear in reply to Smokeypurple]

I agree. It is so easy to think these familiar food items cannot be overdosed, but when they have medicinal qualities, moderation is in order.

[HekateMoon]

Thank you for sharing Pb! Apart fom ashwaghanda i dont use neither quercetin nor acai...i'm still navigating my way with lots of other supplements and dosages without overdosing underdosing or clashing supplements. At the moment taking breaks and slowly reintroducing them and observing...a big interesting journey. Im glad you overcame your symptoms! 🙏😊💫

[Missy0202]

thanks for taking this on and for the warnings. I’m sorry you experienced a decline, even for a short time.

[wriga]

Thanks for this post Park_Bear, and the reminder that when it comes to drugs, even plant-based drugs like sulforaphane, dosing can be critical and difficult to get right. The link you gave to the work we have been doing is still valid, but in the two years since that post, we have made considerable progress, both on understanding the way sulforaphane works but also on the principles guiding dosing, both in terms of quantities and frequency.

Upregulating Nrf2 sets in motion a complex process of transcription of more than 300 genes involved in protecting cells from oxidative stress and mitochondrial dysfunction. This process leads to the production of antioxidant enzymes with a half-life of several days. Overdosing can occur when the frequency of ingestion of activators of Nrf2 fails to take account of the long life of these enzymes. When that happens, as Park_Bear indicates, feedback loops kick in and reverse the positive action of Nrf2 with very unpleasant effects. I have experienced that too with similar results as P_B.

We have now constituted a group to research this subject in more detail. One observation we have made is that certain symptoms are more susceptible to respond to sulforaphane than others. Our research is therefore focused on groups of people with a common dominant symptom that responds to sulforaphane and also has a high impact on Quality of Life. The first symptom group we are looking at is one of the most distressing, but least talked about among People with Parkinson's, Urinary Urgency.

The group is called the Broccoli and Sulforaphane Research Group for Parkinson's disease and now has about 50 active members.

If you're interested, take a look at the website whuch now has a wealth of information on Parkinson's disease and Nrf2 written in plain language for non scientists.

You should start here

patientresearcher.com/

but also look around at the many pages and documents on the subject.

If you want to learn about how the Pharmaceutical industry carefully avoids getting involved in protecting neurons from oxidative stress damage, you might want to read this.

patientresearcher.com/2022/...

Wriga.

[park_bear in reply to wriga]

Thanks for all your efforts to improve our health!

[LAJ12345]

I wonder if when dosing these things it starts off cycles and processes that find a deficiency in some other factor , eg a vitamin or mineral, causing a bad reaction . If that is given at the same time it might get past that block ok until it eventually discovers the next roadblock. Once the process is working again and all factors are available the amount might be able to be increased.

I don’t have any papers to back this up, just a thought.

[Router_]

interesting, I have been using acai for about 2 weeks at 3g with no negative side effects. Will try to reduce a little. Had a positive consistent impact on gut / stool.

[park_bear in reply to Router_]

I did experience a similar benefit which seems to have continued.

[RonB1 in reply to Router_]

I have been taking these supplements for about 2 weeks, with no negative side effects:

Acai Berry (capsule) 500mg

Quercetin 250mg

Ashwagandha 125mg

Emodin 250mg

Although I believe I experienced B1 HCL overdose a while back. I was doing bi-weekly Intravenous infusions of B1 (100mg) and Glutathione (2g). I stopped the B1 IV for now.

[DeanGreen]

Thanks for sharing your Acai experience. I have noticed that some foods exacerbate my PD symptoms and it takes about a week to recover. The one thing these foods have in common is that they are high in oxalates. Soluble oxalates can bind with calcium and become insoluble (crystallize) inside a cell (neuron) and destroy it (apoptosis). This may be a coincidence, but Acai berries are very high in oxalates and may have contributed to your motor deterioration. Just something else to ponder over, as if we already have enough to ponder over in trying to figure out this crazy disease.

[park_bear in reply to DeanGreen]

Interesting. Are there any studies that show that oxalates destroy neurons? Personally, I tolerate spinach okay and spinach is very high in oxalates.

[DeanGreen in reply to park_bear]

There are a few studies that show significantly more oxalate crystals in the brains of PD cadavers. Although I like spinach, it makes my symptoms worse, so I avoid it along with other high oxalate foods. People susceptible to kidney stones are recommended a low oxalate diet. Therefore I was wondering if folks on this diet are less likely to have PD? I was also wondering if people with chronic kidney stones are protected from the effects of oxalate crystals in the brain since the oxalates crystallize in the kidney instead.

[ryant123 in reply to DeanGreen]

Hello, regarding thinking of oxalate, calcium oxalate. I did a search of vitamin k2 oxalate, and, oxalate candida. nourishingtime.com/how-to-d...

[ElliotGreen in reply to DeanGreen]

I might expect that people who have kidney stones might be *more* prone to calcium oxalate deposition in the brain.

Vitamin K2 is necessary to activate enzymes which grab calcium ions where they crystallize and cause problems (e.g. kidneys and blood vessels), and put the calcium where it is needed (e.g. teeth and bones).

It stands to reason that people who have problems with inappropriate deposition in one part of the body might have the same problems in another part of the body. Both might be due to low vitamin K2 levels, for example.

[ElliotGreen in reply to DeanGreen]

Here is a study of four PD cadavers, finding calcium oxalate and titanium dioxide crystals in the striatum negra. Notably, I don't think they used healthy controls.

pubs.acs.org/doi/full/10.10...

This mouse model study did use healthy controls as a comparison, and found more calcium oxalate in the Parkinson's-simulated mice.

mdpi.com/2076-3921/10/7/109...

This quote is interesting:

"Oxidized oxalate may then be deposited in the form of microparticles. Interestingly, the deposition of microparticles of calcium oxalate has been reported in the brain and meninges of patients with primary hyperoxaluria with focal microglial reaction [102], and in the brain of Parkinson’s disease patients [61]. It is known that these crystalline particles of calcium oxalate can activate the inflammasome [61], induce oxidative stress by activating the NADPH enzyme, and cause mitochondria dysfunction, which then contributes to cell damage [103,104]."

[DeanGreen in reply to ElliotGreen]

Thanks very much for the references. Seems like oxidative stress leads to misfolded proteins leading to an autoimmune response. Maybe calcium oxalate is involved in this sequence of events or not. I just bought some "Oxalate Scavenger" which is Vit B6 (pyridoxine), calcium, zinc, magnesium in a herbal blend. I will see how this works.

[ElliotGreen in reply to DeanGreen]

Vitamin C works as an antioxidant but oxalate is left over and can react with calcium to form crystals.

[park_bear in reply to DeanGreen]

Some important information about different varieties of B6 and their toxicity or non-toxicity:

healthunlocked.com/cure-par...

[ElliotGreen]

I take quercetin (500 mg) and bromelain (100 mg) most days. Any thoughts on dosage? This is half of the recommended serving size. I might take more if they were cheaper.

[park_bear in reply to ElliotGreen]

500 milligrams may be a bit high, but if you have been taking it for more than 3 weeks without any adverse affect you are likely okay.

[DeanGreen]

Does anyone here experience a higher frequency of ocular migraines when taking acai, moringa, or resveratrol? Also, I have been prescribed Escitalopram oxalate (Lexapro) for depression and it seems that my symptoms has worsened. Has anyone experienced this?

PS....I had my DBS surgery Friday and looking forward to my first programming session in a few weeks.

[park_bear in reply to DeanGreen]

I suggest asking these questions in a separate post of their own to get better attention.

[laglag in reply to DeanGreen]

How did your DBS surgery go? 🥊🥊

[DeanGreen in reply to laglag]

The surgery went very well and my bald head healed up nicely. That was last Oct. 2022. Now I go in periodically to optimize the programing. After DBS, I do not require Sinemet at all. In fact, Sinemet makes me unbalanced and I tend to stumble around like a drunk person and my speech is somewhat slurred. After DBS, my blood pressure was more stable and I stopped taking Lexapro (Don't need it). So far, I can't complain. I am thankful to be healthy enough to have the surgery.

[laglag in reply to DeanGreen]

That is wonderful !

[Gigi216]

Thank you! I regularly take ashwanganda!

[Gcf51]

I decided to try and cut back on some of my supplements. Ashwagandha got added back due to increased tremor in a matter of weeks.

[Gcf51]

What is your opinion of Loin's Mane?

[park_bear in reply to Gcf51]

Sorry, have not researched it.

[Gcf51 in reply to park_bear]

Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines ncbi.nlm.nih.gov/pmc/articl...

I haven't read much of that I get overloaded with too much medical/research/technical jargon.

[park_bear in reply to Gcf51]

For Parkinson's, the relevant section of this review is:

4.2. Protection against Parkinson's Disease

which cites only one study as follows:

"Results showed that dopaminergic lesions and oxidative stress in the stratum and substantia nigra were significantly improved after pretreatment with 3 mg/g erinacine A-enriched H. erinaceus mycelia for 25 days [39]" [emphasis added]

Pre-treatment is not a valid model of Parkinson's. I explain why here:

healthunlocked.com/cure-par...

So although it is possible that lion's mane might help, we have at hand no valid evidence to this effect.

[PDCyclist]

Dear Mr Bear, as far as ashwagandha goes vs Acai, if it is 7 x 'stronger' would you say that 100mg dried root powder is a good starting dose? (available capsules all seem to be around 1g or more). I tried Acai about a year ago and used ca. 4g daily in porridge - can't say it did any good or bad though - at least it didn't make me gag like broccoli seeds do !

[park_bear in reply to PDCyclist]

Considering that the available capsules are all much higher than that, 100 mg ought to be safe. I did try ashwagandha at one time and it did not do anything for me. I did not note my dosage but I believe it was higher.