Monaural Beats 40 HZ Sawtooth.mp3 played on Portable Mini USB FM Radio Speaker Music Player

Monaural Beats 40 HZ Sawtooth.mp3 played on Portable Mini USB FM Radio Speaker Music Player
I am starting to use this $14 gadget to play the audio file:
https://youtu.be/f2XU8d6ydbw

Portable Mini USB FM Radio Speaker Music Player $14: https://www.amazon.com/gp/product/B00KCIW7KG/ref=ppx_yo_dt_b_search_asin_title?ie=UTF8&th=1
Exact 40 Hz Gamma Brainwave audio used by MIT to prevent Alzheimer’s.mp3 - https://drive.google.com/file/d/16cAxDy8KM8zQB7Xf9Dl7VKQ48Jk6hgBx/view?usp=share_link
Monaural Beats 40 HZ Sawtooth.mp3 (I created this MP3. It has not been validated in studies) - https://drive.google.com/file/d/1RdUlpuwve7ZBbH1GX7tHIcArFS1IbCVN/view?usp=share_link

40 HZ MP3 without the audio book included

Somebody asked me for a 40 HZ MP3 without the audio book included:

Exact 40 Hz Gamma Brainwave audio used by MIT to prevent Alzheimer’s.mp3 - https://drive.google.com/file/d/16cAxDy8KM8zQB7Xf9Dl7VKQ48Jk6hgBx/view?usp=share_link

Monaural Beats 40 HZ Sawtooth.mp3 (I created this MP3. It has not been validated in studies) - https://drive.google.com/file/d/1RdUlpuwve7ZBbH1GX7tHIcArFS1IbCVN/view?usp=share_link

All My Brainwave Entrainment is 40 HZ now

This will be a very incoherent post. My brain is all over the place. So let's go!

(Supporting documents will be listed at the bottom of the page)

1: All My Brainwave Entrainment is 40 HZ now. I have been reading about evidence that 40 HZ is the frequency that seems to have some benefit for AD and PD. Apparently with AD and PD (and maybe other neurological diseases) the brain gamma waves weaken and these weak gamma waves actually allow neurodegeneration. Testing finding that boosting the gamma waves is possible. Therefore I am converting all my binaural beats MP3s to 40 HZ (as opposed to the current 10 HZ 40 HZ combo files).

I have posted my first all 40 HZ binaural beats files: Evolution of Symbolism by Helena Blavatsky - https://drive.google.com/drive/folders/1PTsmEtR0MaH4BmcfWCoRJP3osz7vWZQI?usp=share_link

2: I have also discovered there is a LOT more work being done in brainwave entrainment using monaural beats than using binaural beats. Actual trials using 40 HZ monaural sound, lights, and tactile. This is (supposedly) a link to the actual 40 HZ clicking monaural audio MIT used in their trials: https://youtu.be/UVne_84qZkA

Personally, I find that 40 HZ clicking annoying, and as I do have a High School Degree I went ahead and made my own 40 HZ monaural audio files using a 40 HZ sawtooth wave with an audio booked dropped in: Elementary Theosophy - https://drive.google.com/drive/folders/1-JIX5sCXBM_Cz0eHjk9cYATAgsduKhsC?usp=share_link

One thing about monaural beats is you do not have to use headphones (but I usually do use headphones)

3: I have added a 40 HZ flickering light to my arsenal. MIT did a study with 40 HZ flickering light synchronized with that 40 HZ clicking sound on mice and had success. I bought this $60 flickering bulb: https://www.amazon.com/dp/B08X4W6N5M?psc=1&ref=ppx_yo2ov_dt_b_product_details

I can't synchronize my light and sound so I do them separately (I am looking into whether synchronization really matters). I did find this gadget, but don't plan on buying it: Gamma Audio-Visual Stimulation Coupled Audio-Visual Sensory Stimulation C.A.S.S. Entrainment Device $230 https://www.gammalightandsound.com/

You might see some apps and YouTube videos that say they flicker at 40 HZ, but unless your screen refresh rate is (I think) 180 HZ you won't really get 40 HZ.

Supporting Documents:

☐ The Effects of Long-Term 40-Hz Physioacoustic Vibrations on Motor Impairments in Parkinson’s Disease: A Double-Blinded Randomized Control Trial 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349639/

☐ High Frequency Light, Sound, and Tactile Stimulation to Improve Motor and Cognitive Deficits in Parkinson's Disease 2022 https://clinicaltrials.gov/ct2/show/NCT05268887

☐ GENUS, for Gamma ENtrainment Using Sensory stimuli. https://picower.mit.edu/innovations-inventions/genus

☐ Small studies of 40Hz sensory stimulation confirm safety, suggest Alzheimer’s benefits https://picower.mit.edu/news/small-studies-40hz-sensory-stimulation-confirm-safety-suggest-alzheimers-benefits

☐ Gamma Audio-Visual Stimulation Coupled Audio-Visual Sensory Stimulation C.A.S.S. Entrainment Device $230 https://www.gammalightandsound.com/

☐ TED Talk: Could we treat Alzheimer's with light and sound? Li-Huei Tsai https://www.ted.com/talks/li_huei_tsai_could_we_treat_alzheimer_s_with_light_and_sound/transcript?language=en

☐ Stimulating the brain at 40 Hz to treat Alzheimer’s disease 2023 https://physicsworld.com/a/stimulating-the-brain-at-40-hz-to-treat-alzheimers-disease/

☐ Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies 2021 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0278412

☐ Does Synchronizing Brain Waves Bring Harmony? 2021 https://www.alzforum.org/news/conference-coverage/does-synchronizing-brain-waves-bring-harmony

☐ Researchers propose ultrasound stimulation as an effective therapy for Alzheimer's disease in new study 2022 https://www.sciencedaily.com/releases/2022/01/220124103914.htm

☐ Exact 40 Hz Gamma Brainwave audio used by MIT to prevent Alzheimer’s https://youtu.be/UVne_84qZkA

A little counterpoint on 40 HZ being the best:

☐ Optimal flickering light stimulation for entraining gamma waves in the human brain 2021 https://www.nature.com/articles/s41598-021-95550-1

Although light flickering at 40 Hz reduced Alzheimer’s disease (AD) pathologies in mice by entraining gamma waves, it failed to reduce cerebral amyloid burden in a study on six patients with AD or mild cognitive impairment. We investigated the optimal color, intensity, and frequency of the flickering light stimulus for entraining gamma waves in young adults. We compared the event-related synchronization (ERS) values of entrained gamma waves between four different light colors (white, red, green, and blue) in the first experiment and four different luminance intensities in the second experiment. In both experiments, we compared the ERS values of entrained gamma waves between 10 different flickering frequencies from 32 to 50 Hz. We also examined the severity of six adverse effects in both experiments. We compared the propagation of gamma waves in the visual cortex to other brain regions between different luminance intensities and flickering frequencies. We found that red light entrained gamma waves most effectively, followed by white light. Lights of higher luminance intensities (700 and 400 cd/m2) entrained stronger gamma waves than those of lower luminance intensities (100 and 10 cd/m2). Lights flickering at 34–38 Hz entrained stronger and more widely spread beyond the visual cortex than those flickering at 40–50 Hz. Light of 700 cd/m2 resulted in more moderate-to-severe adverse effects than those of other luminance intensities. In humans, 400 cd/m2 white light flickering at 34–38 Hz was most optimal for gamma entrainment.

Curcumin Update 2023/03/06

Curcumin

Last Updated: 2023/03/06
Status: In my stack as of 2023/03/05
Dose: 1 gram of Meriva Curcumin twice a day with a fatty meal.
Source: Doctor's Best Curcumin Phytosome with Meriva: $35 for 180 500 mg capsules: https://www.amazon.com/dp/B008YDH4HM?psc=1&smid=ATVPDKIKX0DER&ref_=chk_typ_imgToDp

The case for Curcumin:

1 gram of Meriva Curcumin twice a day with a fatty meal for 12 months improved non-motor symptoms, slowed worsening of motor symptoms, and showed a tendency to decrease misfolded α-syn deposits in skin nerves (1).

• A 2022 study evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients not treated with curcumin (1).
• The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study (1).
• Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed:
• A decrease of COMPASS-31 and NMSS scores (1).
• A slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses (1).

• Note: Simon in The Science of Parkinson's reads this study differently and believes the p-syn load increased for both the treated and untreated, it just increased more in the untreated. I have reached out to the paper's author (1).

• PD patients supplemented with curcumin, despite a stable L-dopa dosage, showed an improvement of nonmotor scales while the worsening of the motor scale was less than expected in the control patients who, by contrast, increased their dosage of L-dopa (1).

• Curcumin chelates iron (4).
• Curcumin inhibits EBV in vitro (8):

• Curcumin Suppresses Proliferation of NPC Cells Positive for EBV (8).
• Curcumin Enhances NPC Cell Apoptosis via Mitochondria- and Death Receptor-Dependent Pathways (8).
• Curcumin Downregulated EBNA1 Expression Levels in NPC Cells Positive for EBV (8).
• Curcumin Reduces Stability and Promotes Proteasomal Degradation of EBNA1 (8).
• Curcumin could inhibit EBV+ HONE1 and HK1-EBV cell proliferation, probably via decreasing EBNA1 expression (8).
• Curcumin Inhibits Replication of EBV in NPC Cells Positive for EBV (8).
• Epstein–Barr nuclear antigen 1 (EBNA1) is a multifunctional, dimeric viral protein associated with Epstein–Barr virus (EBV). EBNA1 is integral to many EBV functions including gene regulation, extrachromosomal replication, and maintenance of the EBV episomal genome through positive and negative regulation of viral promoters.

• Curcumin Reduces Oxidative Stress (9).
• Curcumin Diminishes the Inflammatory Cascade (9).
• Curcumin Has a Protective Effect on the Integrity of the BBB (9).
• Curcumin Improves Mitochondrial Dysfunction and Calcium Overload (9).


Notes:
• Disease duration seems important for the curcumin supplementation, as PD patients with shorter disease duration presented a better clinical outcome (1).
• PD patients supplemented with curcumin, despite a stable L-dopa dosage, showed an improvement of nonmotor scales while the worsening of the motor scale was less than expected in the control patients who, by contrast, increased their dosage of L-dopa (1)
• Curcumin with Broccoli Seed Extract extends Drosphila Melanogaster lifespan more than either supplement alone (5).
• Is able to cross the blood-brain barrier in the form of its active metabolites when formulated in phospholipids (1).
• Is effective in ameliorating/stabilizing motor and nonmotor symptoms in PD (1).
• Shows a tendency to decrease misfolded α-syn deposits in skin nerves (1).

References:

1. The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study 2022 https://academic.oup.com/jnen/article/81/7/545/6585246 Vincenzo Donadio, MD, PhD, IRCCS Istituto delle Scienze Neurologiche, Bologna, Italia, via Altura 3, 40139 Bologna, Italy; E-mail: vincenzo.donadio@unibo.it

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

2. An Overview of Parkinson's Disease: Curcumin as a Possible Alternative Treatment 2022 https://www.cureus.com/articles/96465-an-overview-of-parkinsons-disease-curcumin-as-a-possible-alternative-treatment#!/

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain and basal ganglia, followed by dopamine deficiency in the brain. Dopamine plays a crucial role in motor coordination, memory, and cognition; its decrease in PD leads to dyskinesia, cognitive deficits, and depression. In addition, the formation of alpha-synuclein protein aggregates (Lewy bodies) causes further damage to the CNS. Current treatment options include dopamine precursors, inhibitors of dopamine metabolism, upregulation of autophagy, adenosine A2A antagonists, and surgical intervention as a last resort. A challenge arises from a progressive decrease in treatment efficacy as the disease progresses and this necessitates exploration of adjunctive treatments. Epidemiological studies suggest that the prevalence of PD varies between ethnic groups of Caucasians, Asians, and African Americans. Notably, the prevalence of PD is lower in countries of Southeastern Asia including India. The differences in the diet of various ethnic groups may suggest an origin for this difference in the prevalence of PD. One staple ingredient in traditional Asian cuisine is turmeric. Curcuma longa, popularly known as turmeric, is an orange tuberous rhizome that has been used for centuries in traditional Indian cuisine and traditional medicine. Turmeric contains curcumin, a potent antioxidant that scavenges reactive oxygen species and chelates toxic metals. Curcumin has been proposed to be a neuroprotective agent due to its potent antioxidative properties. Though preliminary studies in animal model systems have suggested a protective effect of curcumin on dopaminergic neurons, the direct benefits of curcumin on the progress of PD remains poorly understood. In this review, we explore the promising use of curcumin as an adjunct to conventional PD treatments in order to enhance treatment and improve outcomes.

3. Curcumin Prevents Aggregation in α-Synuclein by Increasing Reconfiguration Rate 2012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308736/

α-Synuclein is a protein that is intrinsically disordered in vitro and prone to aggregation, particularly at high temperatures. In this work, we examined the ability of curcumin, a compound found in turmeric, to prevent aggregation of the protein. We found strong binding of curcumin to α-synuclein in the hydrophobic non-amyloid-β component region and complete inhibition of oligomers or fibrils. We also found that the reconfiguration rate within the unfolded protein was significantly increased at high temperatures. We conclude that α-synuclein is prone to aggregation because its reconfiguration rate is slow enough to expose hydrophobic residues on the same time scale that bimolecular association occurs. Curcumin rescues the protein from aggregation by increasing the reconfiguration rate into a faster regime.

4. Iron chelation by curcumin suppresses both curcumin-induced autophagy and cell death together with iron overload neoplastic transformation 2019 https://www.nature.com/articles/s41420-019-0234-y

Iron overload, notably caused by hereditary hemochromatosis, is an excess storage of iron in various organs that causes tissue damage and may promote tumorigenesis. To manage that disorder, free iron depletion can be induced by iron chelators like deferoxamine that are of increasing interest also in the cancer field since iron stock could be a potent target for managing tumorigenesis. Curcumin, a well-known active substance extracted from the turmeric rhizome, destabilizes endoplasmic reticulum, and secondarily lysosomes, thereby increasing mitophagy/autophagy and subsequent apoptosis. Recent findings show that cells treated with curcumin also exhibit a decrease in ferritin, which is consistent with its chemical structure and iron chelating activity. Here we investigated how curcumin influences the intracellular effects of iron overload via Fe-nitriloacetic acid or ferric ammonium citrate loading in Huh-7 cells and explored the consequences in terms of antioxidant activity, autophagy, and apoptotic signal transduction. In experiments with T51B and RL-34 epithelial cells, we have found evidence that curcumin-iron complexation abolishes both curcumin-induced autophagy and apoptosis, together with the tumorigenic action of iron overload.

5. Antioxidant Blend of Curcumin and Broccoli Seed Extract Exhibits Protective Effect on Neurodegeneration and Promotes Drosophila Lifespan 2021 https://journals.sagepub.com/doi/full/10.1177/17590914211015033

Antioxidants and related compounds are anti-inflammatory and exhibit great potential in promoting human health. They are also often considered to be important elements in the process of neurodegeneration. Here we describe a antioxidant blend of Curcumin and Broccoli Seed Extract (BSE). Flies treated with the blend exhibit extended lifespan. RNA-seq analysis of samples from adult fly brains reveals a wide array of new genes with differential expression upon treatment with the blend. Interestingly, abolishing expression of some of the identified genes in dopaminergic (DA) neurons does not affect DA neuron number. Taken together, our findings reveal an antioxidant blend that promotes fly longevity and exhibits protective effect over neurodegeneration, demonstrating the importance of antioxidants in health and pathology.

6. Essential turmeric oils enhance anti-inflammatory efficacy of curcumin in dextran sulfate sodium-induced colitis 2017 https://www.nature.com/articles/s41598-017-00812-6

Turmeric has been used as a medicinal herb for thousands of years for treatment of various disorders. Although curcumin is the most studied active constituents of turmeric, accumulating evidence suggests that other components of turmeric have additional anti-inflammatory and anti-tumorigenic properties. Herein, we investigated anti-inflammatory efficacy and associated gene expression alterations of a specific, curcumin preparation containing essential turmeric oils (ETO-curcumin) in comparison to standard curcumin at three specific doses (0, 5, 25 or 50 mg/kg), in an animal model of dextran sodium sulfate (DSS)-induced colitis. The present study showed that both ETO and standard curcumin treatments provided protection against DSS-induced inflammation. However, ETO-curcumin improved disease activity index (DAI) dose-dependently, while the anti-inflammatory efficacy of standard curcumin remained constant, suggesting that ETO-curcumin may provide superior anti-inflammatory efficacy compared to standard curcumin. Gene expression analysis revealed that anti-inflammatory cytokines including IL-10 and IL-11 as well as FOXP3 were upregulated in the colon by ETO-curcumin. Collectively, these findings suggest that the combined treatment of curcumin and essential turmeric oils provides superior protection from DSS-induced colitis than curcumin alone, highlighting the anti-inflammatory potential of turmeric.

7. Protective Effects of Indian Spice Curcumin Against Amyloid Beta in Alzheimer’s Disease 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796761/

The purpose of our article is to assess the current understanding of Indian spice ‘Curcumin’ against amyloid-β (Aβ)-induced toxicity in Alzheimer’s disease (AD) pathogenesis. Natural products, such as ginger, curcumin and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, anti-oxidant, anti-arthritis, pro-healing and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on amyloid-β and curcumin has revealed that curcumin prevents amyloid-β aggregation and crosses the blood brain barrier (BBB), reach brain cells and protect neurons from various toxic insults of aging and amyloid-β in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin’s bioavailability and urgent need for new formulation to increase its brain levels to treat patients with AD.

8. Curcumin Inhibits Proliferation of Epstein–Barr Virus-Associated Human Nasopharyngeal Carcinoma Cells by Inhibiting EBV Nuclear Antigen 1 Expression 2019 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800953/

This investigation aims to study the effect of curcumin on the proliferation, cycle arrest, and apoptosis of Epstein–Barr virus- (EBV-) positive nasopharyngeal carcinoma (NPC) cells. EBV+ NPC cells were subjected to curcumin treatment. The cell viability was evaluated with the CCK-8. Cell cycle and apoptosis were analyzed by flow cytometry analysis. Expression (protein and mRNA) levels were detected with western blotting and quantitative real-time PCR, respectively. Curcumin efficiently reduced the viability of EBV+ NPC cells. Curcumin induced the cycle arrest of the HONE1 and HK1-EBV cells positive for EBV. Moreover, curcumin treatment promoted the NPC cell apoptosis, via the mitochondria- and death receptor-mediated pathways. Furthermore, curcumin decreased the expression of EBNA1 in the HONE1 and HK1-EBV cells and inhibited the transcriptional level of EBNA1 in the HeLa cells. Curcumin induced EBNA1 degradation via the proteasome-ubiquitin pathway. In addition, curcumin inhibited the proliferation of HONE1 and HK1-EBV cells positive for EBV, probably by decreasing the expression level of EBNA1. In both the HONE1 and HK1-EBV cells, curcumin inhibited the EBV latent and lytic replication. Curcumin could reduce the EBNA1 expression and exert antitumor effects against NPC in vitro.

9. Mechanisms Underlying Curcumin-Induced Neuroprotection in Cerebral Ischemia 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090137/

Ischemic stroke is the leading cause of death and disability worldwide, and restoring the blood flow to ischemic brain tissues is currently the main therapeutic strategy. However, reperfusion after brain ischemia leads to excessive reactive oxygen species production, inflammatory cell recruitment, the release of inflammatory mediators, cell death, mitochondrial dysfunction, endoplasmic reticulum stress, and blood–brain barrier damage; these pathological mechanisms will further aggravate brain tissue injury, ultimately affecting the recovery of neurological functions. It has attracted the attention of researchers to develop drugs with multitarget intervention effects for individuals with cerebral ischemia. A large number of studies have established that curcumin plays a significant neuroprotective role in cerebral ischemia via various mechanisms, including antioxidation, anti-inflammation, anti-apoptosis, protection of the blood–brain barrier, and restoration of mitochondrial function and structure, restoring cerebral circulation, reducing infarct volume, improving brain edema, promoting blood–brain barrier repair, and improving the neurological functions. Therefore, summarizing the results from the latest literature and identifying the potential mechanisms of action of curcumin in cerebral ischemia will serve as a basis and guidance for the clinical applications of curcumin in the future.

Want to know the differences and details of all of the NAD+ precursors?

 

Trp (Tryptophan), NA (Nicotinic Acid), NAM (Nicotinamide), and NR (Nicotinamide Riboside)? They are surprisingly different:

Balancing NAD+ deficits with nicotinamide riboside: therapeutic possibilities and limitations 2022 https://link.springer.com/article/10.1007/s00018-022-04499-5

Nicotinic Acid still looks like the best option to my High School educated brain.

If I was smarter, I might not be so excited about Niacin. I am pretty excited.

 

If I was smarter, I might not be so excited about Niacin. I am pretty excited.

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications 2019 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/

"Parkinson’s disease (PD) is a progressive disorder characterized by degeneration of dopaminergic neurons within the substantia nigra, whose main hallmarks are abnormal aggregation of the α-synuclein protein, inhibition of mitochondrial respiratory complex 1, oxidative stress and neuroinflammation. Because only 5–10% of PD cases can be ascribed to genetic predisposition, several environmental factors may play a role in sporadic forms of PD [149]. Among them, vitamin B3 is a promising preventive and therapeutic factor (Table 1), as it can alleviate certain types of early-onset PD symptoms. NAD+ levels, indeed, fall in patients with PD and, conversely, increasing niacin intake can increase dopamine synthesis in the striatum and restore optimal NAD+/NADH ratio needed for the activity of mitochondrial complex 1 [148]. High niacin levels can also sequester transition metal ions (including iron) that usually accumulate together with the occurrence of aggregated misfolded proteins [149,150]. Furthermore, optimal levels of vitamin B3 are needed for reducing oxidative stress and neuroinflammation, also implicated in PD pathogenesis: low doses of niacin alter macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenothype, while exogenous NADPH suppresses oxidative stress and glia-mediated neuroinflammation [151,152].

Neurons are the only cells of the brain expressing NNMT that seems to play an important role in sustaining neuron homeostasis [153]. Despite numerous investigations, the exact cause-effect relationship between NNMT and PD neuropathogenesis remains unclear. Some authors refer to NNMT as a risk factor for PD, since its levels are elevated in the cerebrospinal fluid and midbrain dopamine neurons of PD patients [153,154]. High NNMT activity is associated with low activity of mitochondrial complex 1, thus providing a link with mitochondrial dysfunction triggering neurodegeneration [154,155]. It is noteworthy that N1-methylnicotinamide (the metabolite generated by the action of NNMT) is structurally similar to N-methy-l-4-phenylpyridinium (MPP+), a toxin damaging dopamine neurons [168]. Conversely, other studies have demonstrated that the enzyme is able to (i) counteract the MPP+-mediated toxicity on mitochondrial complex 1, (ii) activate neuronal autophagy for balancing energy sources and cell homeostasis, and (iii) modulate neuron morphology and differentiation, by inducing neurite branching, synaptophysin expression and dopamine accumulation and release [156]. Likewise, NAD supplementation or inactivation of NAD-consuming enzymes [like PARP-1, a poly(ADP-ribose) polymerase involved in DNA repair] rescue mitochondrial defects and protect neurons against degeneration, in familial forms of PD characterized by mutations in the pink1 gene; this finding suggests that neurotoxicity associated with mitochondrial defects may be prevented by modulating NAD+ salvage metabolism in order to enhance NAD availability [169]."

Interesting table: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/table/ijms-20-00974-t001/?report=objectonly

Lots of digging to do.

Upping My Niacin to 1000 mg

Update 01/22/2023:

I just learned there is an increased risk of diabetes on niacin therapy: https://heart.bmj.com/content/102/3/198
This study was based on people taking Niacin for cardiovascular reasons, which I think would be dosed at 500 to 6000 mg a day: https://www.mayoclinic.org/drugs-supplements/niacin-oral-route/proper-use/drg-20065086
According to this video you should be able to eliminate the diabetes risk by not having carbs 3 to 6 hours after your niacin, therefore I will start taking my 1000 mg of niacin after my last meal of the day: How to Take Niacin Without Getting Diabetes https://youtu.be/76mrnovnGQ4

EVERYBODY: FEAR THE FLUSH. DON'T TRY TO START AT 1000 MG. DO YOUR RESEARCH.

I have a high school degree. Caveat Emptor. 

I hope everybody is taking Nicotinic Acid.

I've been taking 250 mg of Niacin (Nicotinic Acid) every day ever since this study came out in June of 2021: Niacin Enhancement for Parkinson’s Disease: An Effectiveness Trial - https://www.researchgate.net/publication/352486597_Niacin_Enhancement_for_Parkinson's_Disease_An_Effectiveness_Trial

In this study 47 people took 250 mg of slow release (no flush) Nicotinic Acid for 12 months and all of their UPDRS scores improved (except executive function). Pretty dramatic success.

So... I started on 250 mg time released (could not find slow release) and then switched to fast release (flushing) as I heard time released is not good for the liver (allegedly).  I am no worse than I was 18 months ago.  Probably a little better.  

I should add: I have not been diagnosed with PD. I have RBD, a sore left shoulder and left leg, face dandruff, get dizzy when I stand, and have random involuntary movements. I can say "had" to most of those conditions: My RBD is now very mild and rare. Random involuntary movements are rare. I don't get dizzy when I stand. My face dandruff is better but still there. My sore shoulder is still sore, but not as bad. I have gone back to using a mouse left handed after a year of going right handed.  I should also add: I do a lot of things besides Niacin.

So why am I taking this dose up to 1000 mg? Because I've been looking at papers that show Nicotinic Acid may be able to:

• Cure Systemic NAD+ Deficiency.
• (PwP have low NAD+).
• Treat mitochondrial myopathy.
• Boost Mitochondrial Biogenesis.
• Restore the BBB integrity. 
• This is pretty cool. I had not seen anything capable of maybe fixing the blood brain barrier.
  

These all look like good things to me.

 

So here are the papers:

Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy 2020
https://www.sciencedirect.com/science/article/pii/S155041312030190X

• "NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open. Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750–1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy."
• This is an article about the same paper: Vitamin B3 Boosts Muscle Health in Mitochondrial Myopathy, Study Suggests 2020
  https://mitochondrialdiseasenews.com/2020/05/15/vitamin-b3-niacin-aids-muscle-metabolism-in-mitochondrial-myopathy-pilot-study-suggests/

 

Niacin mitigates blood–brain barrier tight junctional proteins dysregulation and cerebral inflammation in ketamine rat model of psychosis: Role of GPR109A receptor 2022
https://www.sciencedirect.com/science/article/abs/pii/S0278584622000756

• Male Wistar rats Niacin 40 mg/kg/day. Divide by 8 for Humans and you get 5 mg per kg. For 70 kg human dose would be 350 mg.
• "Niacin also augmented the hippocampal expression of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the BBB integrity."

 

Niacin improved rigidity and bradykinesia in a Parkinson's disease patient but also caused unacceptable nightmares and skin rash--a case report 2005
https://sci-hub.se/10.1080/10284150500484638

• "At a routine primary care visit, niacin was increased to 500 mg twice a day for triglyceride reduction. At a three-month follow-up, his family reported he was now initiating many routine activities of daily living that previously required their prompting. At this office visit, on exam he could rise from a chair independently and start walking with minimal latency. Previously, he needed the examiner to lend him a hand to get up, and he took a few seconds to start walking. Rigidity was noticeably diminished."

Progresses in both basic research and clinical trials of NAD+ in Parkinson’s disease 2021
https://sci-hub.se/10.1016/j.mad.2021.111499

• "These studies indicate disturbances in NAD+ metabolism as a common feature in cellular and animal models of PD and point toward NAD+ supplementation as a valuable therapeutic approach to boost mitochondrial function and halt DA neurodegeneration. However, additional studies are needed to further substantiate the relationship between NAD+ levels and PD onset and progression".

 

These 3 studies and the case study all used Nicotinic Acid, not NR and not NMN. Plain old cheap Niacin.

 

Why am I going with 1000 mg a day?

• My lack of education makes me think more is better.
• The "Niacin Cures Systemic NAD+ Deficiency..." study used 750 to 1000 mg.
• The case report from 2005 used 500 mg twice a day.
• And I will throw in the NADPARK study (ClinicalTrials.gov: NCT03816020) where they went with 1000 mg of NR a day.
• I know this is not niacin, but it is close to niacin.
  

Dave