Homocysteine and Metabolic Alzheimer's

January 11, 2016

Metabolic Alzheimer’s: Why Homocysteine Matters 

 References:   Bredesen Aging 2015, NEJM 2002, AJCN 2005, Hooshman Neurology 2010 

 First of all, do you know what Homocysteine is?   It’s a fairly simple concept. It is an amino acid that you have in every cell in your body. It swaps a methyl group back and forth with methionine, and passes it off in a pathway that begins with B12 and folate.   The next step is to make cysteine, and then glutathione.   Glutathione is the ultimate “detox” compound.   You want that to happen efficiently. It converts many compounds in your body to water soluble forms, and able to be excreted. In effect, you are getting rid of “gunk”, metabolic breakdown products.   Homocysteine backs up when you aren’t doing that efficiently enough. Higher levels of homocysteine, in effect, mean you aren’t getting enough B12 and activated folate, both of which are the sources of methyl groups.   And the net effect you see if higher irritation and inflammation in blood vessels and brain.

 Homocysteine, by itself, isn’t bad. It is just an indicator of how efficiently you are getting rid of “gunk” and how smoothly you are passing on used chemicals. This is where it turns interesting. Bredesen, at UCLA, has been thinking about Alzheimer’s and finding that there are many paths to a common end. What looks like one disease in it’s final stages, with memory loss and shrinking brains, may in fact be the common endpoint of several distinct pathways.   In his landmark paper (in my humble opinion) he documents the three patterns of Alzheimer’s that he has been observing. The first type might be termed inflammatory with high C-reactive protein and abnormal albumin/globulin ratios: markers of inflammation. 

The second would be metabolic. This is where diabetes and insulin resistance come in, along with low Vitamin D, low sex hormones and inadequate B vitamins, which shows up with high homocysteine levels. The final type might be called toxic, and affects all parts of the brain, happens to younger folks and is often associated with very low zinc levels. It shows up with slightly different symptoms – not being able to calculate math or find words as well. How does homocysteine fit in Alzheimer’s?   It has been shown to increase all sorts of pathways that drive the brain pathology of Alzheimer’s. And when measured, it has been shown to have a linear risk associated with it.   

This might be the take home lesson.   Having a low homocysteine is highly desirable.   Hooshman in Neurology published a paper showing that homocysteing increases of 1 mg per deciliter resulted in a 16-19% increased risk of Alzheimer’s. Ouch.   And this corroborates earlier studies like Sehsadri in the NEJM that shows a doubling of risk by increases from 7 to 15.   If your level is 15 and you want to make an impact on your future risk for Alzheimer’s, getting your homocysteine down to 7 might be one of the more effective strategies. And how do you do that? Most of the time, it comes down to more B12 and activated folate.   Remember all those old country doctors that used to give B 12 shots that we ridiculed? Hmmm.   Perhaps they are chuckling in their graves right now. 

 WWW. What will work for me. This is simple. I already take a B12 supplement. I lowered my homocysteine last year by 3 points and then haven’t measured it since. Going forward, I am adding it to my annual lab panel.   

 Pop Quiz

  1. Homocysteine is a poison in your body that you want to get rid of?   T or F
False. It is a simple mid-path indicator of metabolic efficiency.
  1. It explains all cases of Alzheimer’s. T or F
False. That would be overreaching. But it may be central to a metabolic explanation of one type.
  1. Lowering your homocysteine might be a critically important means of avoiding Alzheimer’s. T or F
False. Not proven yet. It is an association. But it’s very strong evidence.
  1. My doctor wants to give me B12 shots. Is she crazy?
No, maybe more forward thinking than we thought
  1. I can get B12 from eating a clean, vegan diet. T or F
False. No B12 at all in plants. Have to have animal or specialized yeast extracts.