34 replies to this topic

[pamojja]

"Thanks for the link pamojja.  The second one to your stack says I don't have permission to view / No stacks match that id provided?

 

Funny error, the link still works for me. One can also reach it by hovering over 'Collaborate' in the upper horizontal menu bar, there click on 'Regimens'. There sort by 'Stack Rating', and then its the 5th entry titled with 'PAD and additional Remissions'.

[StanG]

"I'm aware of that line of reasoning (basically, mouse gut bacteria convert choline to TMAO, but not human gut bacteria) and I really want to believe it because I want to supplement with choline for several reasons.

 

But, there's this:

 

Gut Microbe-Generated Trimethylamine N-Oxide From Dietary Choline Is Prothrombotic in Subjects
 

These guys fed choline to real humans (herbivores and omnivores) and measured a 10x increase in plasma TMAO levels, so I don't know that the idea that humans don't metabolize choline to TMAO is supportable.

 

Which is shame since I think that choline has many positive aspects as a supplement.  But if this study is right I think daily supplementation with choline can be problematic.

 

I wish it were not so."

 

Thanks for this. Here are my notes on Choline. I've been taking it twice weekly which makes sense to me and I don't see why a person simply can't take it less often. It isn't just what you take and the dosage, it's also HOW OFTEN you take it.

 

"

*Choline – a B vitamin - 500mg(telomerase activator?) – NEXT TIME BUY SWANSON’S ULTRA-AHPHA GPC ASIT IS RATED BEST!

Studies in humans have shown that neither phosphatidylcholine nor choline-rich foods produce detectable increases in trimethylamine.

A 1999 study by other authors came to similar conclusions.  They looked at the urinary excretion of both trimethylamine and its detoxification product TMAO in humans.  They found that 60 percent of free choline and 30 percent of carnitine, another potential precursor, was excreted in the urine as one of these two products, but that neither betaine nor phosphatidylcholine converted to either product at all.

These authors even fed 46 different foods to humans and looked at the subsequent excretion of trimethylamine and TMAO.  Choline-rich foods like liver and eggs did not produce any increase in urinary trimethylamine or TMAO over control levels.  In fact, even carnitine-rich meats failed to increase excretion of these compounds.  The only foods that increased excretion of TMAO were seafoods, which naturally contain some trimethylamine, giving them their “fishy” smell.

Indeed, the massive increases in urinary trimethylamine and TMAO following meals rich in seafood suggests that our kidneys excrete these compounds very efficiently.

 

Nice one. I hadn’t gotten to that paper yet, beyond noting that the amount of choline they fed to the mice was massive. Needless to say, I was finding their claims hard to swallow on that basis alone… (a paper that refuted the initial research as being faulty) Take twice weekly!

, "Another remarkable finding is that choline -- a natural semi-essential vitamin -- when taken in excess, promoted atherosclerotic heart disease.

Choline-fuelled signalling molecules are at the seat of learning, memory and behavior. As a result, there has been a lot of buzz around manipulating cholinergic neuronal transmission in order to slow or undo the neurologic effects of aging.

The tricky part is not how much choline can be pumped into the brain, but how efficiently this critical raw material can be transported to various regions of the brain. Otherwise, it's like gassing up a car that has a clunked out engine.

 

A large problem in aging and diseased brains is the slowing of cholinergic transport, while cholinergic neurons drop in number. In Alzheimer's disease, cholinergic cells shrivel up and die at a fast-forward pace. Scientists believe that even in healthy aging people, malfunctioning and decreased numbers of choline-powered neurons are somewhat to blame for short-term memory loss and cognitive decline.

*Uridine 250mg –. Take with Choline. Emerging evidence suggests that uridine is a neuroactive molecule, which is involved in the regulation of certain neural functions apart from its role in pyrimidine metabolism. Uridine has sleep-promoting and anti-epileptic effects, might affect mood, improves memory function and influences neuronal plasticity." 

 

 

 

[Dorian Grey]

The study showing high levels of TMAO used choline bitartrate and not lecithin/phosphatidylcholine.  Believe the studies using lecithin show much more benign effects regarding TMAO.  

 

Lecithin is a much better form of choline to supplement with anyway.  The body seems to prefer this form.  Don't have a link handy, but I've read choline bitartrate has actually raised liver enzymes, whereas liver's love lecithin.  

[albedo]

Probably IP6 for lowering ferritin going from as high as 450ng/ml to <=100ng/ml (2006-2017). This is confounded though with other supplements and lifestyle changes to control and lower inflammation of which ferritin  is a typical biomarker next to CRP, leucocytes, fibrinogen and others which might also be organ specific.

 

Comforted in what I am trying to do against inflammation and reducing ferritin reading this paper on impact on mortality which finally is what really matters. I try to stay at <= 100mcg/L while they seem to use 2x that a threshold value:

 

Ellervik C, Marott JL, Tybjærg-hansen A, Schnohr P, Nordestgaard BG. Total and cause-specific mortality by moderately and markedly increased ferritin concentrations: general population study and metaanalysis. Clin Chem. 2014;60(11):1419-28.

 

"...Moderately to markedly increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population..."

 

"...Multifactorially adjusted hazard ratios (HRs) for total mortality for individuals with ferritin ≥200 vs <200 μg/L were 1.1 (95% CI 1.1-1.2; P = 0.0008) overall, 1.1 (1.0-1.2; P = 0.02) in men, and 1.2 (1.0-1.3; P = 0.03) in women. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10(-22)), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400-599 μg/L, 76 years at 200-399 μg/L, and 79 years at ferritin <200 μg/L. The corresponding HR for total overall mortality for ferritin ≥600 vs <200 μg/L was 1.5 (1.2-1.8; P = 0.00008). Corresponding adjusted HRs for ferritin ≥600 vs <200 μg/L were 1.6 (1.1-2.3; P = 0.01) for cancer mortality, 2.9 (1.7-5.0; P = 0.0001) for endocrinological mortality, and 1.5 (1.1-2.0; P = 0.01) for cardiovascular mortality. The metaanalysis random effects odds ratio for total mortality for ferritin upper vs reference quartile or tertile was 1.0 (0.9-1.1; P = 0.3) (P heterogeneity = 0.5)..."

 

 

[Dorian Grey]

Thanks for this albedo.  Here's yet another paper with some statistics on ferritin levels and disease.  Glad you've gotten this under control.  

 

http://www.yourhealt...ives/ihn241.pdf

 

ASSOCIATION AND THRESHOLDS OF FERRITIN LEVELS AND RISK OF VARIOUS DISEASES 

 

From studies in a recent systematic review, threshold ferritin levels for increased risk of incidence of type 2 diabetes were for women, 86, 107,122, 134, 150 and. For men 184,209, 215, 229, 300.  

 

The ferritin threshold for the increased risk of any coronary calcium was >257 in a study of over 12,000 men. 

 

In a study of men and postmenopausal women a ferritin threshold of >200 was associated with an increase in heart attack risk.  

 

A study classified CHD-positive patients as having one or more coronary arteries with ≥ 50% blockage. Comparison of ferritin levels revealed that those CHD-positive had on average ferritin levels of 121 vs. 73 for those CHD negative by this measure.  

 

A study of ferritin levels as a risk factor for the metabolic syndrome found thresholds of >89 for premenopausal women, >212 for post-menopausal women but found no association for men.9 In another study, low levels (30-42) of ferritin in premenopausal women were found to not be associated with the risk of metabolic syndrome but for postmenopausal women, a significant risk had a threshold of >52. 

 

At a ferritin threshold of >137 increased risk of ischemic stroke (occlusive) was found in a study of postmenopausal women. 

 

A ferritin threshold of >145 to >164 was found for increased risk of acute ischemic stroke transforming to a hemorrhagic stroke in older men and women. 

 

Inspired by the fact that iron overload can cause cardiomyopathy, a large study examined the association between ferritin levels and laboratory measured cardiovascular fitness (CVF) in young men. The likelihood of not having CVF, adjusted for numerous potential confounders, became significantly apparent at a ferritin threshold of >150.   

 

Significant risk of middle-aged men developing hypertension defined as ≥ 140/90 mm Hg had a ferritin threshold level > 146.

 

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Perhaps association doesn't equal causation?  Does lowering ferritin really help?

 

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FERRITIN THRESHOLDS FOR BENEFIT IN IRON LOWERING STUDIES:

 

Iron reduction in smokers with peripheral arterial disease reduced the risk of death or nonfatal heart attack such that the number needed to treat to prevent one acute event with blood-letting was only 8. The initial and final mean ferritin levels were >125 and 84

 

In a group of patients who were either diabetic or carbohydrate intolerance, lowering mean ferritin from 272 to 45 resulted in an increase in HDL and reductions in blood pressure, triglycerides, fasting blood glucose and an improved oral glucose tolerance test.

 

A trial involving blood-letting for a group of men and women with the metabolic syndrome which decreased ferritin levels from a mean of 188 to 105 found a decrease in systolic blood pressure from 149 to 131 mm Hg with no change in a control group. Blood glucose, HbA1c and heart rate were also significantly decreased

 

Aggressive blood-letting reduced the ferritin from 220 to 13 in patients with non-alcoholic fatty liver disease who were glucose intolerant. The result was near normalization of a serum marker for liver function and a 40-50% improvement in fasting glucose and glucose stimulated insulin

 

Use of the oral prescription chelator deferiprone over 9 months reduced ferritin from 144 to 59 and resulted in significant improvements in patients with non-diabetic kidney disease

 

Blood donation which resulted in ferritin levels on average decreasing from a median of 130 to 84, significantly increased HDL levels from 37 to 41 measured at 6 to 8 weeks after the last donation

 

In a trial of phlebotomy in patients with peripheral artery disease, a reduction in mean ferritin levels from a baseline of 122 to 74 resulted in a significant reduction in the incidence of visceral malignancy

 

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You may not notice the effects of iron chelators (IP6, Curumin, & Quercetin), but apparently they are very real!  

Edited by Dorian Grey, 11 January 2018 - 12:19 AM.