CSF Ferritin predicts cognitive decline in E4s

[Tincup]

George I think you'll be impressed by the DIY approach.

Love it!!!!

[Stavia]

George I think you'll be impressed by the DIY approach.

Love it!!!!

Thought you would

[James]

I don't see the value of checking the serum ferritin level. It does not tell you the brain iron status.

I agree that serum (plasma) ferritin says very little about CSF ferritin. The original paper does not provide actionable information for non-researchers - it simply adds CSF ferritin to the well-established associations among CSF APOE, ε4 status, and AD risk and adds a hypothesis (brain iron overload causes AD) to the stack of promising AD-related areas to investigate.

This might be the best we have--see supplementary figure 3. Associations between CSF ferritin and plasma ferritin.
https://www.ncbi.nlm.nih.gov/pmc/articl ... 760-s1.pdf

From the paper:

Plasma ferritin levels were not associated with plasma ApoE levels or APOE ɛ4 allele status (Supplementary Fig. 2), but there was a modest association between plasma ferritin and CSF ferritin levels (β=0.075, P=0.0002; Supplementary Fig. 3).

Keep in mind that this is for all subjects, and that those with ApoE4 had higher CSF ferritin. Though there's no way of knowing how the relationship between plasma ferritin and CSF ferritin is impacted by ApoE status. It might be prudent to assume those with ApoE4 fall in the higher end of the range.

Figure 1. CSF ferritin associates with ApoE levels and varies according to APOE genotype.
https://www.ncbi.nlm.nih.gov/pmc/articl ... figure/f1/

[Stavia]

Interesting, thanks James.
I'm thinking that our DIY venesection would be neutral at worst....possibly like a lot of other things we do....

[KatieS]

Thanks, James for finding a reference correlating, albeit weak, between the serum & CSF ferritin. Add this to all the benefits of low ferritin that MarkR posted.

In my above reference related to HFE, they state without a citation that those with the less common C282Y (rs1800562 A/G) have some dementia "protection" (but increased cancer risk) unlike the more common H63D carriers.

[slacker]

Interesting, thanks James.
I'm thinking that our DIY venesection would be neutral at worst....possibly like a lot of other things we do....

I currently work for a gastroenterologist who specializes in Hepatitis B and C (blood born viruses affecting the liver). It is not unusual to see new patients with ferritin in the 600-1000 range. They are sent for "therapeutic phlebotomy" (the US term) even without hereditary hemochromatosis status. We expect ferritin to drop 200-400 points per 5mL (pint) of blood, targeting "normal" range. Some patients are sent for phlebotomy weekly for 4 weeks due to severity of elevation, with hemoglobin checked prior to taking blood. No further blood is drawn if the patient is anemic.

I believe the theory is that the excess iron is stressing the liver in addition to the viral infection. I'm not sure that there is any "proof" for this. Ferritin is a known "acute phase reactant" ie another marker of inflammation. I have noticed that the ferritin levels tend to improve by treating the infection, and wonder (in this population) whether the phlebotomy is needed.

This interesting Australian link discusses the relevance of ferritin from a conventional perspective, indicating that 90% of people with elevated ferritin do not have iron overload. It also discusses other reasons for elevated ferritin:
http://www.racgp.org.au/afp/2012/decemb ... -ferritin/

Just more grist for the mill...

[Jafa]

Hey Slacker, thanks for the very interesting post. Can't wait to have time to read the Aussie data.

[Stavia]

Slacker, 200 points drop per 500ml? You mean 20? How quickly does it drop?
Jafa, I'm feeling fine, how you feeling?

[MarcR]

That's a fascinating document, slacker. On the topic of insulin resistance / sensitivity, the authors point the arrow of causation in the opposite direction from Francesco Facchini (Gastroenterology and also British Journal of Nutrition):

AFP: improve insulin sensitivity => reduce iron stores
Facchini: reduce iron stores => improve insulin sensitivity

The AFP authors define iron overload restrictively and thereby justify the denial of phlebotomy treatment to almost everyone. Unless the patient has hereditary haemochromatosis or ferritin > 1000 (!!!), phlebotomy won't help - stop drinking alcohol and eat better! Illogically, they recommend that donation-eligible patients give blood every 12 weeks. The article reads like a policy justification.

In contrast, Facchini conducted experiments and reported results. His subjects were insulin resistant with normal iron levels. Using phlebotomy to reduce iron to near-deficiency dramatically improved insulin sensitivity.

And then there's the whole issue of using ferritin as a surrogate for iron stores. The AFP authors say it requires genetic testing, a suite of four iron-related blood tests, and a thorough examination of lifestyle factors. Facchini relied mostly on ferritin, but in one of the studies he also monitored iron saturation and MCV.

[Jafa]

Hi Stavia, Yeah feeling great. Apart from the sleep issue. Bloody humidity doesn't help eh? No supplements for that. Must listen to the Masterjohn video.