As previously mentioned in my posts ... I am not officially dx'd with PD. I have PD-like symptoms which I've held in 'check' since my self-diagnosis (and self-treatment) on June 20, 2021.
One of the supplements that Dr Hyman recommends in the above video is: choline.
I just spent about an hour researching 'what kind' of choline, this is a commercial website selling a product but it has good info about choline types...:
i bought this one from Amazon because of its touted purity and it is MADE in the USA:
Toniiq Ultra High Purity Alpha GPC Capsules - 600mg Concentrated Formula - 99%+ Highly Purified and Highly Bioavailable Nootropic - 120 Capsules Alpha GPC Supplement
As of today, 5.7.23 -- the Amazon web page is offering $10 discount and since I'm taking over 40 supplements daily... saving a few bucks is always nice.
Cytidine - The precursor to nucleotide uridine, a key factor in synaptic strength and neural connectivity, a powerful nootropic on its own.
While citicoline possesses less choline per serving than alpha-GPC, the combination of choline and cytidine is a potent, powerful tool of cognitive enhancement that exceeds the standard benefits of choline, namely within the realms of brain energy and repair.
Altogether, citicoline's two-in-one design seems possess three key bio-benefits:
Neurotransmitter Synthesis - citicoline potentially improves ACh production while increasing dopamine release.
Synaptogenesis Promotion - uridine may promote and sustain the creation of neural synapses, alleviating neurodegenerative conditions.7
ATP and Phosphocreatine - MRS testing revealed a 14% ATP increase and a 7% phosphocreatine increase with citicoline supplementation.8
Citicoline's diverse biomechanisms qualify the nootropic not only as an acute cognitive enhancer but a long-term brain repair nutrient, granting it a unique status as a universal nootropic compound.
the reason i went with this one... Toniiq Ultra High Purity Alpha GPC
1. displayed the authenticity certificate on the Amazon web page guaranteeing 99% purity ... I've never seen another supplement on Amazon 'show' that... and this product is made in the good, old ... USA
Alpha-GPC - 40% choline density; able to cross the blood-brain barrier.
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So it has more than double the choline 'density' of citicoline
3. I was very troubled by one of the PubMed reviews about how citicoline (I didn't post that one, sorry -- i'll try to find it and post here later) -- caused some sort of TMAO (i can't explain it here, but it was bad for our health) and something else that studies had shown serious health side effects....
But that article went on to say that other studies contradicted that study.
So when I'm confused about putting something into my body -- I don't do it
"The issue of hypothetical citicoline resistance to intraintestinal hydrolysis is of importance when we consider that the intestinal microbiome metabolizes a significant fraction of choline and its derivatives to trimethylamine (TMA), a gaseous metabolite readily taken up and oxidized in the liver to its N-oxide, TMAO."
"TMAO has been implicated in the etiology of various diseases, such as kidney failure, diabetes, and cancer [33]. There is a large and growing amount of literature on the atherogenicity of TMAO resulting in increased incidence of myocardial infarction, stroke, or death [34]. A meta-analysis published recently led to the conclusion that higher plasma TMAO correlates with a 23% increase in risk for cardiovascular events and a 55% increase in all-cause mortality [35]. Two recent reports showed that higher TMAO levels were associated with increased risk of first ischemic stroke and worse neurological deficit [36], and that patients suffering from atrial fibrillation who developed cardiogenic stroke displayed approx. 4 times higher TMAO levels in plasma than patients with atrial fibrillation who did not develop stroke [37]. Another recent report suggested a link between TMAO and Alzheimer’s disease [38]. It has even been suggested that supplementation with choline esters prone to be metabolized to TMA and TMAO, such as phosphatidylcholine, may be dangerous to human health [39]."
Wait a minute... The rest of that section you quoted contradicts the beginning:
"On the other hand, several observations cast doubt on the pivotal role of TMAO in atherosclerosis. First of all, nutritional intakes of TMAO and its precursors do not always correlate with cardiovascular disease risk. For example, high fish intake increases TMA/TMAO while being cardioprotective. Some hypotheses have been proposed recently to resolve this paradox, employing inter alia a phenomenon of reverse causality, a possible role of insulin resistance and diabetes mellitus in activating N-oxidation of TMA, etc. [40].
Nonetheless, many authors still take it as having been proven that TMAO is a causative factor in the development of atherosclerosis and cardiovascular diseases. For example, in a recent review on TMAO and stroke [41], several reports are quoted that show the importance of TMAO as a risk factor and prognostic marker for this disease, and indicate the pathomechanisms involved. These include increased TMAO generation promoting atherosclerosis, platelet activation, and inflammation. The author concludes that TMAO may be a central molecule in the relationship of diet, genetics, the gut microbiota, and cardiovascular disease.
It may be concluded that until the place of TMAO in the chain of events leading to cardiovascular diseases and mortality is ultimately clarified, citicoline could be a more reasonable choice than other choline compounds, when choline supplementation is indicated."
Altogether, whereas the jury may still be out on the issue whether, or to what extent, citicoline taken orally is metabolized to TMA and TMAO, there are reasons to believe that procognitive effects of citicoline supplementation are superior over those of choline or phosphatidylcholine."
"Therefore, it might be expected that supplementation with choline will improve cognitive performance. However, trials in which the effects of oral supplementation of humans with choline or phosphatidylcholine on cognition were investigated yielded mixed, mostly negative results (see [45] and references cited therein). On the other hand, in a recent small placebo-controlled study, adolescent males treated with citicoline showed improved attention and psychomotor speed and reduced impulsivity [46]. In other recent controlled studies, citicoline seemed to be efficacious in adult patients suffering from cognitive impairments, especially of vascular origin [47]. These newer studies corroborated results obtained previously when citicoline as a prescription drug had been tested in several placebo-controlled trials for cognitive impairment due to chronic cerebral disorders in the elderly. The review of those early trials led to the conclusion that there was some evidence of a positive effect of citicoline on memory and behavior in at least the short to medium term [48]. Moreover, it was recently shown that in patients suffering from dementia concomitant oral intake of citicoline improved the efficacy of cholinesterase inhibitors [49,50]."
I am not trying to convince you to take Citicoline. It just seems to me that paper is saying Citicoline might be safe, might not be, but Citicoline is the only Choline worth taking. I have a HS degree, so take this with a truckload of salt.
If you are taking your D3, as every person with PD should, that should be enough to significantly reduce TMAO levels as discussed in this study via altering specific bacteria in the gut microbiome :
' The results indicate that the HC (high choline) group exhibited higher plasma trimethylamine (TMA) and TMAO levels, lower richness of gut microbiota, and significantly increased Firmicutes and decreased Bacteroidetes as compared with group C. Vitamin D supplementation significantly reduced plasma TMA and TMAO levels in mice fed a high-choline diet. Furthermore, gut microbiota composition was regulated, and the Firmicutes/Bacteroidetes ratio was reduced by vitamin D. Spearman correlation analysis indicated that Bacteroides and Akkermansia were negatively correlated with plasma TMAO in the HC and HCD3 groups. Our study provides a novel avenue for the prevention and treatment of CVD with vitamin D. '
The accompanying graph from the study shows how vitamin D microbiome alterations reduces TMAO levels.
These are other important reasons why PwPs should be taking their D3 :
Good lord, that's exceptionally high vitamin D3 supplementation for both the control (1000 IU vitamin D3/kg diet)) and the rest D3 groups (2000 IU vitamin D3/kg), while practically guaranteeing the 2nd HC group was D deficient for 4 months for strictly controlled young mice - why not 1000IU as in the control? Even using BSA normalization to reduce the dosage, human equivalent is over 12,000 to 24,000 IU of D3 minimum. This mouse study may have limited relevance or direct applicability to humans who tend to consume much lower choline and D3 dosages.
While it is definitely important not to be deficient in D, vitamin D3 should only be supplemented depending on serum test level as too high a level also impacts health negatively. Here's a human study for D supplementation on TMAO.
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