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Choline levels associated with higher mortality

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So taking choline supplements is probably suicidal LOL!
Br J Nutr. 2019 Jul 10:1-9. doi: 10.1017/S0007114519001065. [Epub ahead of print]

Dietary choline is positively related to overall and cause-specific mortality: results from individuals of the National Health and Nutrition Examination Survey and pooling prospective data.

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Key State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, People's Republic of China.
Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK.
Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland.
Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.


Little is known about the association between dietary choline intake and mortality. We evaluated the link between choline consumption and overall as well as cause-specific mortality by using both individual data and pooling prospective studies by meta-analysis and systematic review. Furthermore, adjusted means of cardiometabolic risk factors across choline intake quartiles were calculated. Data from the National Health and Nutrition Examination Survey (1999-2010) were collected. Adjusted Cox regression was performed to determine the risk ratio (RR) and 95 % CI, as well as random-effects models and generic inverse variance methods to synthesise quantitative and pooling data, followed by a leave-one-out method for sensitivity analysis. After adjustments, we found that individuals consuming more choline had worse lipid profile and glucose homeostasis, but lower C-reactive protein levels (P < 0·001 for all comparisons) with no significant differences in anthropometric parameters and blood pressure. Multivariable Cox regression models revealed that individuals in the highest quartile (Q4) of choline consumption had a greater risk of total (23 %), CVD (33 %) and stroke (30 %) mortality compared with the first quartile (Q1) (P < 0·001 for all comparison). These results were confirmed in a meta-analysis, showing that choline intake was positively and significantly associated with overall (RR 1·12, 95 % CI 1·08, 1·17, I2 = 2·9) and CVD (RR 1·28, 95 % CI 1·17, 1·39, I2 = 9·6) mortality risk. In contrast, the positive association between choline consumption and stroke mortality became non-significant (RR 1·18, 95 % CI 0·97, 1·43, P = 0·092, I2 = 1·1). Our findings shed light on the potential adverse effects of choline intake on selected cardiometabolic risk factors and mortality risk.

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So taking choline supplements is probably suicidal LOL!
Maybe. Note, that it says "dietary choline intake" - now, perhaps here they don't distinguish between dietary and supplemental, which is entirely possible - although at that point it would've been preferable if they didn't mention "dietary" at all, and simply focused on serum levels; they mention "consumption" which I suppose might mean including supplemental? You mention taking choline supplements - I wonder how many people in all these studies supplement with choline; I suspect almost all subjects consumed choline in their diet and the numbers of people who supplemented with choline was too small to have any power to draw contrasting conclusions from.
What I wonder is to what degree the deleterious effect of choline was due to choline itself, and to what degree perhaps it's a confounder, in that perhaps it's simply a marker for the foods in which choline is present (as mentioned, supplementation with choline is likely a very rare occurance). In other words, what if the damage is due to whatever else it is that rides along with choline rather than the choline itself. So, if you get all of your choline from dietary sources, perhaps it's whatever else that might be in those foods - some of the high choline foods are eggs, meats and so on. Furthermore, if you are consuming foods that don't promote TMAO gut biome bacteria - say, largely vegetarian - then supplementing with choline might have a different effect on the biome; we know that the gut produces no/less TMAO on a vegetarian diet, or a diet that includes certain vegetables such as brassica that seem to stop a lot of TMAO production. Now, TMAO is just one example of what can be produced from choline, there may be other things which are deleterious from choline consumption, but again might be modiefied by some other dietary or lifestyle factor. 
It's entirely possible that how choline impacts your health is dependent on your physiology. For example, it says: "we found that individuals consuming more choline had worse lipid profile and glucose homeostasis" - what if due to your overall diet, exercise and lifestyle choices, you do NOT have a bad lipid profile and glucose homeostasis despite supplementing with choline? If some of the damage from choline consumption is mediated through a bad lipid profile or glucose homeostasis, then if you don't have those negative consequences, supplementing with choline is harmless for you.
Bottom line, there is a lot we don't know here. And taking choline supplements is a particular unknown compared to diet. Therefore, I'd invert your quote. I'd rather say "Perhaps consuming a lot of choline in your diet might be deleterious, but whether supplementing with choline is bad for you might perhaps depend on the rest of your diet and lifestyle choices". YMMV.
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I wasn’t totally serious of course. That’s why there is an lol. But your points are worthy and heck it’s complicated, but IAC  supplementation of any kind has rarely, very rarely been shown to confer benefit for most people and sometimes harm. but that’s generally only when megadosing  which we are not discussing wrt choline I don’t think. For me I’ll just stick to a whole food, plant based diet And furthermore I’m quitting the 4 eggs a week I was eating in a desperate attempt to get enough choline. I like Dean Pomerleau’s idea of giving up on the goal of getting the rda for choline and simply eating a healthy whole food, plant based diet and getting 300ish mg of choline. I think this study lends support to Dean’s thinking on this.

Edited by mikeccolella
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21 minutes ago, mikeccolella said:

For me I’ll t

just stick to a whole food, plant based diet and chuck the supplements using chronometer to insure adequacy.

MMMmmm....., I too am heading that way. Supplements, besides having variable concentrations of the declared molecules, may contain various impurities among which heavy metals contamination. Especially those whose active principles are coming from China and India. And most of them are, as we know from the recent investigations of generic pharmaceuticals.

I just wouldn't know how to minimize the probability of contamination. Purchase the most expensive products? But who guarantees that they are simply poorly controlled products with hefty costs? Reliable brands like Pure encapsulation or Jarrow? The same may apply, without updated certificates.

We only have some guarantees of a known, uniform chemical composition probably without contaminants, in non-generic pharmaceuticals.

Bottom line, I'm trying to use only the supplements which may be absolutely useful, like D3 in wintertime, or which may be useful to correct some known deficiencies or surpluses like homocysteine.

The knowledge of food chemistry and the use of specific applications like cronometer makes it viable to minimize the use of supplements.

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  • 6 months later...
20 minutes ago, InquilineKea said:

if you're vegan it isn't an issue cuz vegans lack the TMAO-producing gut microbia


That may not be true.  Look at the  studies posted here.

To cut to the chase, TMAO researcher Stanley L. Hazen,  (M.D., Ph.D.,  chair of Cellular and Molecular Medicine, and section head of Preventive Cardiology & Rehabilitation at the Cleveland Clinic in Ohio) puts it this way:


"It's a fallacy to think if you're a vegetarian or vegan you can't have a high TMAO," Hazen clarified. "There's a ton of choline in gallbladder juice, so you're constantly feeding choline to your gut microbes, even when you eat a cucumber sandwich."


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13 hours ago, Sibiriak said:


That may not be true.  Look at the  studies posted here.

To cut to the chase, TMAO researcher Stanley L. Hazen,  (M.D., Ph.D.,  chair of Cellular and Molecular Medicine, and section head of Preventive Cardiology & Rehabilitation at the Cleveland Clinic in Ohio) puts it this way:


So, what does this mean for Alpha-GPC supplementation?

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Ron, I don't have any new information since the last time we discussed Alpha-GPC   here.

My overall conclusions on choline/TMAO are:   1) eat a health PB diet, including foods like cruciferous vegetables, garlic, etc. which may reduce TMAO production,  2) only supplement choline  if needed to meet minimal requirements;  3) follow the  European Food Safety Authority (EFSA) Adequate Intake (AI) level for choline  set at 400 mg/day ( even a little less is probably okay),  rather than the higher amounts set by other authorities,  as discussed here.

At that time (August 2019) you concluded:


I've reduced my Alpha CPG dose to 150 (from 300 over the past six months or so), but will continue taking it, since by my count, there are plenty of days I don't hit 400.

Again,  I have no new info to add as I've more or less moved on from the TMAO issue.

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  • 5 months later...

It's possible for anyone with the ApoE4 Alzheimer's risk-increasing allele that choline may be beneficial:


Droplets of Unsaturated Fats Burden Human ApoE4 Astrocytes



"Adding the phospholipid precursor choline to the cells restored their normal lipid metabolism, hinting at potential therapeutic approaches for ApoE4 carriers"


"Choline is a component of Souvenaid, a medical food designed by Nutricia of Danone Research to enhance the formation and function of synapses. In the LipiDiDiet clinical trial, people with AD who consumed this yogurt-like drink once a day for two years had slightly less shrinkage of the hippocampus than did controls. The trial failed to meet its primary outcome, but follow-up data suggested that Souvenaid might help people who continue consuming the drink for three years."




"At three years, the cognitive benefit on the CDR-SB widened for those taking Souvenaid, with decline slowing by 45 percent. Likewise, the rate of hippocampal atrophy diverged further between the groups, slowing by 33 percent for those on Souvenaid. The Cohen’s d effect sizes were 0.31 and 0.27, respectively, for CDR-SB and hippocampal atrophy. Both were significant at the 0.01 level or better."

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