The Homocysteine/AD connection

[MAC]

Great series of papers Juliegee! And all based on nutrient/metabolic focused preventive strategies, not pharma.

Re the Smith presentation on homocysteine/Vitamin B analysis/conclusions. So I get that he presented that lower tHcy was correlated with lower dementia (but no fundamental proven reason why). Then he showed results of trials with folate/Vitamin B which lowered tHcy and dementia, which he universally equated with lower dementia, ie, lower tHcy = lower dementia.

Isn't it possible the the folate/Vitamin B regiment, besides lowering tHcy, manifested an improvement in dementia by some other completely unrelated (i.e. not measured) effect? Why must it be that the folate/Vitamin B regiment is unequivocally connected to dementia reduction via only tHcy reduction (but only for high tHcy participants)?

From what I have read about tHcy and direct AD cause/effect, it still a theory?

[Stavia]

MAC we spoke to Bredesens chief scientist, Dr Rao Ram about this very point. He has found experimentally that amyloid aggregates faster at higher levels of homocysteine. He has chosen a level of 7 as an achievable level that will minimise the effects of homocysteine on amyloid aggregation.

[MAC]

Thanks Stavia, this is published scientific work?

And nowhere/no one else has published any studies trying to validate this "theory"?

This could be a REALLY important metabolic finding re better understanding root cause, so it should have serious scientific work behind it's assertions.

[Stavia]

Mac why do you put the word "theory" in quotations? I am confused.
Are you inferring that in your opinion the homocysteine "theory" is of lesser value than a theory?
Yes of course one intervention may have multiple effects and is likely to rather than just one.
Have you read Drs Refsum and Smiths work?
And Dr Ram is widely published. I have no idea if he is publishing this, he does extensive research in many areas.
You are welcome to email him at the Buck. He likes to chat about his decades of work in the field.

[Stavia]

Ps MAC have you read about methylation? This may better help you understand what homocysteine is a marker of.

[MAC]

Sorry, what I meant, is that the tHcy studies do not absolutely prove a dementia root mechanistic neurodegenerative cause. I have absolutely no theory, just trying to filter for absolute proven mechanisms that gives hope to improved targetted therapeutic result.

[Julie G]

Isn't it possible the the folate/Vitamin B regiment, besides lowering tHcy, manifested an improvement in dementia by some other completely unrelated (i.e. not measured) effect? Why must it be that the folate/Vitamin B regiment is unequivocally connected to dementia reduction via only tHcy reduction (but only for high tHcy participants)?

From what I have read about tHcy and direct AD cause/effect, it still a theory?

Smith and Refsum are certainly moving things from correlation towards causation in very well-controlled studies when age appropriate participants are used, and homocysteine is checked pre and post treatment. And you're correct, only in those with high homocysteine is a positive effect noted. Re. MOA, homocysteine tracks very nicely with multiple markers: cognition, white matter hyperintensities, hippocampal volume, etc. and the trifecta of B's lower homocysteine... but I suppose it could be a red herring. That being said, as someone at very high risk for AD, I'd be hard pressed to NOT maintain low Hcy, but you're welcome to wait until it is proven to your satisfaction.

[MAC]

I think I am being misunderstood. I AM trying to lower my tHcy and pretty much pretty much everything recommended in this forum. I am not waiting for absolute proof or a magic bullet cure...it may never come.

I am just trying to understand where the science is relative to finding definitive root cause(s) of the disease so I (we) can have greater hope in targeted therapeutics.

Us engineers tend to think in black and white, solve problems with defined building block fundamentals. But this bio stuff is infinitely more complicated than my world, it blows my mind!

[Nancy]

Yes! Our bodies and brains are incredibly complex! The science isn't perfect because it comes from people who aren't perfect. I am grateful, though, that some people have the motivation and are able to get the funding to make some progress.

[Julie G]

Thanks for explaining, MAC. None of the interventions we practice (including exercise- our least controversial!) are proven to reverse or prevent AD. And, none of the MOAs of our interventions are fully understood. Biology is infinitely complex and we have so much more to learn. That being said, I appreciate your engineer's mind. IMHO, some of the greatest current thought leaders in health come from the same perspective. If we are to make a dent in AD, a multidisciplinary out-of-the box approach may be necessary. Your questions are very welcome.