http://nutritionfacts.org/video/als-lou-gehrigs-disease-fishing-for-answers/
http://nutritionfacts.org/video/diet-and-amyotrophic-lateral-sclerosis-als/
He does an excellent job telling the story of how the research has progressed and the evidence started coming together, and reviews quite a few more articles than I do here. But I wanted to produce a short written summary for those who don't like videos, and to highlight where I think the data is relatively strong and weak.
Since my professional research focuses primarily on sustainable agriculture, my mother died from ALS, and my grandfather died from Alzheimer's, I have a strong interest in how these topics might intersect. That also means I likely lack the objectivity needed to review this from a completely neutral perspective, but I think the data paint a compelling picture that merits further study.
The basic hypothesis here is that BMAA (β-N-methylamino-L-alanine, a toxin created by cyanobacteria, AKA blue-green algae) forms when algae thrive (often due to excessive nutrient runoff from agriculture), accumulates in seafood, and can cause neurological damage including ALS, Alzheimer's, Parkinson's disease, and similar symptoms. Note that concern over microcystin, which is another toxin produced by cyanobacteria, led to the residents of Toledo being unable to drink their tap water for 48 hours in August of 2014.
Let's take a look at each of the steps in that theory.
Cyanobacteria in Lake Littoistenjärvi, Flickr user Stefe
First, there is strong evidence that consumption of high levels of BMAA is associated with ALS / Alzheimer's. The classic case is in Guam, where incidence of ALS, Alzheimer's, and Parkinson's (referred to collectively as ALS-parkinsonism-dementia complex or ALS-PDC) was abnormally high among the Chamarro people there. These people eat flying foxes (a kind of bat), which in turn eat cycad seeds which are high in BMAA, and the BMAA accumulates in flying fox flesh at levels around 3,500 ug of BMAA per g of flesh (Cox et al. 2003). When you feed BMAA to macaques, they develop similar symptoms (Spencer et al. 1987), and BMAA was detected in brains of people in who died from ALS / Alzheimer's but not in brains of people who died of other causes (Cox et al. 2003, Pablo et al. 2009).
In addition to directly showing high levels of BMAA in the diet and presence of BMAA in brain tissue of symptomatic patients, there is some additional weaker correlative evidence. Torbick et al. 2014 found a correlation between hotspots of ALS and proximity to lakes with high nitrogen and turbidity. This may sound like a stretch, but there is solid evidence showing how nutrient and sediment runoff from agriculture leads to eutrophication and algal blooms in lakes and streams (in addition to hypoxia in the Gulf of Mexico), and since BMAA is produced by blue-green algae this is at least interesting data. Another very small study (Field et al. 2013) looked at three patients who lived on the same short street and all developed ALS (raising the possibility of an environmental trigger given the rarity of ALS). In looking for common factors, they found that all three patients consumed Chesapeake blue crab on a weekly basis, and they verified that these blue crabs had BMAA. However, the levels found (0-115 ug/g in the claws) were significantly lower than in the flying foxes, and some of the BMAA leaches into cooking water meaning the absorbed dose should be lower unless the broth is consumed.
This raises the question of how common seafood with potentially dangerous levels of BMAA is, and the evidence is mixed. On the one hand, Brand et al. 2010 measured BMAA concentrations in several types of seafood in S Florida and found high levels (up to 7,351 ug/g) in some samples of some species (with other samples having lower values or none). They found the highest levels in blue crab, pink shrimp, and one sample of pufferfish), and indeed those levels were higher than that of the flying foxes in Guam. On the other hand, Jiang et al. found BMAA at levels less than 1 ug/g in locally-caught Swedish seafood (although they did find detectable levels in about half of tested samples), and review the results and methods of a few other studies where BMAA levels were much lower than those found by Brand et al. This is an area where we really need more research; both measuring levels of BMAA in seafood, and determining how those concentrations relate to an increased risk of disease.
Finally we have the question of to what degree algal blooms are really associated with BMAA. Scott et al. (2014) found that 70% of the cyanobacteria blooms they sampled had BMAA (compared to 50% with microcystin). Apparently BMAA is produced more under low-nitrogen conditions, while microcystin is produced more under high-N conditions, but interestingly large algal blooms allow both to form simultaneously due to nutrient gradients within the bloom. Again we need more study to determine what drives BMAA production in the first place, and what nutrient levels we should aspire to achieve.
This leads to an alarming possibility: in addition to the potential risk from seafood, the fact that drinking water is generally not tested for BMAA and BMAA can occur even when microcystin levels (which are tested more frequently) are low means we could be missing a risk factor for some serious diseases.
So what are the implications of all this? First, there is enough evidence to raise concerns that consumption of BMAA could be a contributing factor to developing ALS and Alzheimer's disease. Second, while the wide variation in measured levels of BMAA in seafood means more study is needed, the fact that Brand et al. found some levels comparable to the infamous flying foxes in Guam should be motivation to look seriously at this. Third, since eutrophic waters are associated with BMAA production (and thus perhaps with ALS as indicated in the Torbick study), this is one more reason to work on improving agricultural practices to reduce nutrient and sediment runoff.
There are many promising possibilities to reduce nutrient runoff (precision agriculture, riparian buffers and wetlands, changes in cropping systems, changes in irrigation and drainage, and more) and the research is clear that we need different approaches in different contexts. If evidence continues to grow about the link between the way we grow our food and the incidence of ALS and Alzheimer's disease, so will our motivation to take swift and effective action to solve our nutrient runoff problem. Hopefully farmers, conservationists, and health professionals can come together to make that happen.
UPDATE: A more recent paper (Chernoff et al. 2017) has come out which concluded that there was NOT good evidence that BMAA leads to neurological diseases in humans. See https://www.tandfonline.com/doi/abs/10.1080/10937404.2017.1297592 for more detail
Brand, L. E., Pablo, J., Compton, A., Hammerschlag, N., & Mash, D. C. (2010). Cyanobacterial blooms and the occurrence of the neurotoxin, beta-N-methylamino-l-alanine (BMAA), in South Florida aquatic food webs. Harmful Algae, 9(6), 620–635. doi:10.1016/j.hal.2010.05.002
Chernoff, N., Hill, D. J., Diggs, D. L., Faison, B. D., Francis, B. M., Lang, J. R., ... & Schmid, J. E. (2017). A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans. Journal of Toxicology and Environmental Health, Part B, 20(4), 183-229.
Cox, P. A., Banack, S. A., & Murch, S. J. (2003). Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proceedings of the National Academy of Sciences of the United States of America, 100(23), 13380–13383. doi:10.1073/pnas.2235808100
Pablo, J., Banack, S. A., Cox, P. A., Johnson, T. E., Papapetropoulos, S., Bradley, W. G., … Mash, D. C. (2009). Cyanobacterial neurotoxin BMAA in ALS and Alzheimer’s disease. Acta Neurologica Scandinavica, 120(4), 216–25. doi:10.1111/j.1600-0404.2008.01150.x
Scott, L. L., Downing, S., Phelan, R. R., & Downing, T. G. (2014). Environmental modulation of microcystin and β-N-methylamino-l-alanine as a function of nitrogen availability. Toxicon, 87, 1–5. doi:10.1016/j.toxicon.2014.05.001
Spencer, P., Nunn, P., Hugon, J., Ludolph, A., Ross, S., Roy, D., & Robertson, R. (1987). Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science, 237(4814), 517–522. doi:10.1126/science.3603037
Torbick, N., Hession, S., Stommel, E., & Caller, T. (2014). Mapping amyotrophic lateral sclerosis lake risk factors across northern New England Mapping amyotrophic lateral sclerosis lake risk factors across northern New England.
