Comment by burning_hamster | Hacker News Reader

Comment by burning_hamster | Hacker News Reader

burning_hamster

I am not sure I buy into the author's calcineurin/mitochondria hypothesis.

There is a much more direct causal link as auto-immunity has been implicated in AD progression for years, e.g. [1-11]. I can't find the paper right now, but I once saw a very compelling longitudinal study where they regularly measured cognitive performance as well as several immunity markers in older subjects. Basically, every transient increase in antibody levels (IIRC, but they may have been tracking some other marker of immune system activation) was followed by a step decline in cognitive performance.

[1] Lopez (1991) Serum auto-antibodies in Alzheimer's disease

[2] Aisen (1996) Inflammation and Alzheimer disease

[3] D'Andrea (2005) Add Alzheimer’s disease to the list of autoimmune diseases

[4] Carter (2010) Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner

[5] Reddi et al (2011) Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Aβ and RAGE peptides

[6] Sardi et al (2011) Alzheimer's disease, autoimmunity and inflammation. The good, the bad and the ugly

[7] Marchese (2013) Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

[8] Li et al. (2018) Dementia and Alzheimer's disease risks in patients with autoimmune disorders

[9] Arshavski (2020) Alzheimer’s Disease: From Amyloid to Autoimmune Hypothesis

[10] Itzhaki et al (2020) Do infections have a role in the pathogenesis of Alzheimer disease?

[11] Lim et al (2020) Alzheimer Disease Pathogenesis: The Role of Autoimmunity

I absolutely agree with this. My great grandmother had Alzheimers as well as Hidradenitis suppurativa, which I have inherited from her. I switched to a yeast and wheat free diet many years ago to relieve symptoms of HS. Not only did it resolve my HS, but also migraines and many other inflammatory issues. Looks like there is research around Alzheimer's and Dectin-1 signaling which is involved in innate immunity to fungi, including bread yeast (Saccharomyces cerevisiae). It's absolutely insane to me that people eat a pathogen that triggers an innate immune response. A inflammation response to yeast is coded into our cells, if it weren't we'd be killed by unbaked bread. Why then do most processed foods contain it? We're taxing and confusing our immune systems by eating it.

Is there less Alzheimer's in cultures that don't eat bread (e.g. where rice or potatoes are a staple instead)?

Maybe in bread heavy cultures it's not a widespread issue because the majority of people have evolved some kind of resistance?

You tend to get Alzheimer's after you are done having children, so resistance wouldn't evolve.

If that were true humans would die much sooner after becoming infertile.

The fact we stick around for so long is because having healthy grandparents is still beneficial to grandchildrens' survival.

That does not really make sense. Yeast from bread is not really a pathogen. Everything you eat, not just bread, is covered in wild yeast.

Fermented foods, which are largely considered good for heath, are full of yeast.

So you could refine that last bit to

> We're taxing and confusing our immune systems by eating.

if that were truly the case.

> We're taxing and confusing our immune systems by eating.

Well this is not wrong. I'm no expert, but it seems as though not eating (or drinking) would result in less need for inmune system activity, at least in the digestive track. Of course, you'd die, but maybe that was the cost of healthy living all along

This diet is hard to follow because yeast cuts through a lot of foods, especially in fermented foods as you've mentioned. A non-exhaustive list of yeasty foods looks like: Non-distilled vinegars, non-distilled alcohols, dried fruits, naturally-fermented soy sauce, cheese, many savory packaged goods, most vegan meat replacements, some dried spices, bread, etc.

Fermented foods and mushrooms can be good at fighting cancer precisely because they ramp up the immune system. In fact yeast is used as an adjuvant inside of vaccines for this purpose.

What's insane is that it is both known and not known that yeast causes inflammation by science. Used as adjuvant, used to "boost" immunity, yet not understood to be a cause of general low-grade systemic inflammation when in our food supply.

Opportunistic Strains of Saccharomyces cerevisiae: A Potential Risk Sold in Food Products https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705302/

Most cheese, if not all, doesn't have yeast in it. It's bacteria that ferment it.

Though I guess it will have as much wild yeast land on it as any other food in your plate but I don't think that's what the parent comment was referencing.

Source: I've been involved in small commercial cheese making for years.

Umm, yeast is a common surface flora on many cheeses (probably all natural rind cheeses), and you can in fact buy packets of Debaryomyces Hansenii and Candida Utilis from Danisco specifically for use in cheese. Source: I'm involved in cheesemaking.

So what are you proposing? Trying to avoid everything that might cause an immune system reaction? That will eventually lead to the immune system really running amok...

I'm just saying that a wheat and yeast-free diet has reversed Hidradenitis and many systemic inflammation symptoms for me. In trying to understand _why_ it became clear to me that yeast (and maybe wheat) trigger an inflammatory response in our innate immune system - by design. So it's probably not a good idea to eat yeast unless you want to up-modulate your immune system (inducing inflammation). Even if your body can down-modulate, isn't that just causing a sensitivity imbalance similar to diabetes and glucose?

For example, Dectin-1 is one of many innate cellular receptors that launch inflammatory responses when Bread yeast (and others) is detected (and possibly 1,3 beta glucans from wheat). We are in a genetic war with saccharomyces cerevisia, inside of our DNA. And not just us, all animals need to be in this war, because otherwise we'd die.

https://en.wikipedia.org/wiki/CLEC7A

So if all this is true, does it make sense to put yeast extract in your gravy tonight?

Slightly off topic, but if this experiment https://www.thefreshloaf.com/node/37259/mythbusters-grain-ye... is correct, bread yeast is specialized, and doesn't spread by air very well.

I can easily imagine someone with a genetic trait that malforms a single protein could end up with a heritable sensitivity to one particular yeast strain, and not all yeast, everywhere.

This isn’t a well understood area at all but the idea that yeast / fermented food consumption helps us regulate our immune system in a good way has also been studied.

Yep, it's kind of a double-edged sword. On one hand an over-active immune response can be great for fighting cancers and opportunistic infections possibly. But too much inflammation will wear down our bodies and trigger auto-immune responses.

Sorry, haven’t read these yet, but any antibodies? Like any immune response makes you duller and at greater risk? Eek.

Like I said, I can't find the study right now, and I originally saw the data anywhere between 5-10 years ago. They may also have been measuring some cytokine. Even without AD, memories really aren't reliable over that time span.

The point the authors were trying to make is that if you have AD, any inflammation, even asymptomatic ones, will potentially worsen your cognitive performance. The most interesting feature of that graph was to me that the cognitive performance actually remained fairly constant in between infections/inflammations, and decline was not gradual but in a step-wise fashion.

Also interesting is ISRIB [0,1], which is intended to negate the cognitive impacts of stress memory accumulated over years of immune response, and possibly as a result of TBI as well [2].

[0] https://en.wikipedia.org/wiki/ISRIB

[1] https://doi.org/10.1073/pnas.1815767116

[2] https://doi.org/10.1073/pnas.1707661114

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