| Alzheimer’s,
Lou Gehring’s, and Parkinson Diseases in Guam, and the Safety
of Blue-Green Algae
by Christian Drapeau, MSc.
Recently, a group of scientists suggested that all blue-green
algae contained the amino compound ß-methylamino alanine
(BMAA), and that this amino compound could be linked to the development
of Alzheimer’s disease. Headlines warned against the possibility
that waters containing blue-green algae could be linked to Alzheimer’s.
It incidentally raised a concern in the minds of consumers used
to enjoy the health benefits of dietary supplements based on blue-green
algae.
In the reports one of the scientists is quoted saying “the
study does not prove that BMAA plays a role in Alzheimer’s
or other brain disease.” Indeed, the theory proposed by
Cox and colleagues linking BMAA to Alzheimer’s disease is
elegant, but as discussed below, it has little scientific merit.
Like many scientific stories, some background is necessary to
understand what the story is about, and in fact this is a very
interesting story.
Background
In the 1950s a strange neurological problems was reported on the
island of Guam in the Western Pacific. A significant proportion
of adults were developing tremors and problems walking. Histological
observations of their brain showed damages similar to what is
seen in Alzheimer’s disease, though the disease was distinct
from Alzheimer’s. After much investigation the disease was
defined as two different diseases happening simultaneously: a
form of amyotrophic lateral sclerosis (ALS; Lou Gehrig’s
disease) and a Parkinson-like disease coupled with dementia, which
became referred to as parkinsonism-dementia complex (PDC). Rapidly,
the disease of Guam became known as ALS-PDC.
ALS and PDC occur with high frequency among the indigenous Chamorro
population on the island communities of Guam and Rota in the Western
Pacific. At the height of the epidemic, in the 1950s and early
1960s, ALS and PDC each accounted for nearly 25% of all adult
death on Guam. Two other locations with high-incidence of ALS
and PDC have been reported among geographically and genetically
distinct populations in the western Pacific in West New Guinea
and in the Kii peninsula in Japan.
At first, ALS-PDC was believed to be genetic in nature, as it
appeared to run among first degree relatives, but later epidemiological
studies indicated that consumption of traditional Chamorro diet
was the only variable significantly associated with the disease
incidence.
Seeds of cycad plants, Cycas micronesica or Cycas
circinalis, used by the Chamorro people as a source of tortilla
flour, contain several neurotoxins including the non-protein amino
acids ß-methylamino-L-alanine (BMAA) and ß-N-oxalylamino-L-alanine
(BOAA), the amino sugar methylazoxyethanol b-D-glucoside (cycasin),
which is transformed in the body into its aglycone methylazoxymethanol
(MAM), and ß-sitosterol ß-D-glucoside (BSSG). All
these compounds are mild to severe excitotoxins1. But diet also
includes drinking water and the water found in the areas of highest
incidence of the disease, including the Kii peninsula in Japan
where cycad flour is not consumed, is deficient in calcium and
magnesium and contains high levels of aluminum. In feeding trials,
water low in calcium and magnesium and high in aluminum led to
symptoms similar to ALS-PDC.
Various studies have been done to investigate the potential role
of these factors in ALS-PDC in Guam. Interestingly, none of these
factors alone or even a combination of these factors can fully
explain the disease, and this has led to the formulation of a
series of hypotheses.
The theory of bioaccumulation of BMAA
BMAA has been studied by various groups as a potential cause underlying
the development of ALS-PDC, but after careful and thorough investigation
it was abandoned as a possible cause.
First, Chamorro people develop the disease decades after exposure
to the causing agent, as the disease is not seen in young people.
Some people have even developed the disease more than a decade
after leaving the island of Guam. When BMAA was fed to primates
in extremely large quantities, the problems that developed (and
this was seen in only one of the many studies) were not similar
to ALS-PDC and their onset within less than two months did not
parallel the delayed onset seen in ALS-PDC.
Second, consumption of large amounts of BMAA was never linked
to symptoms resembling ALS-PDC. When large amounts of BMAA –up
to 15.5 g/kg- were fed to mice for over 11 weeks, no abnormal
behavior was seen, the animals showed none of the neurological
changes that would be expected in ALS-PDC, and microscopic examination
of the brain and spinal cord showed no abnormalities.
Third, BMAA is much milder than other known excitotoxins to which
large segments of the population are exposed daily. BMAA is an
excitotoxin acting at the NMDA receptor2.
Two of the natural neurotransmitters for the NMDA receptor are
glutamate and aspartate, which are commonly used as artificial
flavoring agent (monosodium-glutamate; MSG) and sweetener (aspartame;
NutraSweet®). In various studies, glutamate and aspartate
were shown to be up to 1,000,000 times more toxic than BMAA. If
consumption of BMAA were to be linked to the development of ALS-PDC
or Alzheimer’s, then entire segments of the North-American
population consuming aspartame and glutamate would develop such
diseases.
The interest in BMAA was recently renewed when Cox and colleagues
proposed that BMAA is not actually produced by cycads but rather
by a symbiotic blue-green algae growing within the root of the
cycad tree. The levels of BMAA found in cyanobacteria cultured
from a cycad tree from Hawaii was 0.3 to 72µg/g, which is
by far too low to be linked to any toxicity. Cox and colleagues
proposed that BMAA’s toxicity comes from the fact that BMAA
accumulates in the roots (2-37 µg/g) and in the cycad seeds
(9 µ/g), and ends up being highly concentrated in the outermost
integument of the seed (1,000 µg/g). Then flying foxes,
a species of bat (Pteropus mariannus), would accumulate BMAA in
their flesh (up to 3,500 µg/g) by foraging on the seeds.
Flying foxes are in turn a delicacy highly prized by the Chamorro
people who boil the animal in coconut milk and eat the entire
animal.
Cox and colleagues suggested that the custom of eating flying
foxes is a possible causal factor in the high incidence of ALS-PDC
in Guam. However, given the general consensus that BMAA doses
of 100 mg/kg/day are believed to be necessary to lead to neurological
problems, this would equate to a consumption over long periods
of time of 9 flying foxes per day, which is unrealistic. Furthermore,
inhabitants of the western Pacific islands in West New Guinea
and in the Kii peninsula in Japan where ALS-PDC has a high incidence
do not consume flying foxes.
To support his hypothesis, Cox and colleagues affirmed that consumption
of flying foxes peaked during the mid-20th century, when after
the war both firearms and disposable cash were available to the
Chamorros, and then declined in the later part of the 20th century
after over-hunting of the flying foxes and their enlisting as
an endangered species in 1984. Cox and colleagues claimed to have
found no historical account of a pandemic neurological disease
among the Chamorros before the 20th century. Given that the pattern
of flying fox consumption seemed to parallel the appearance and
disappearance of ALS-PDC in Guam, Cox and colleagues proposed
that the appearance of the disease during the 20th century was
due to an increase in the consumption of flying foxes in the aftermath
of the military occupation of Guam, and the subsequent demise
of the flying fox population led to the decline in incidence rate
of ALS-PDC among the Chamorros.
This is certainly an elegant hypothesis, but it does not reflect
historical accounts. First, French explorers reported in 1819
that “…cultivation of cycads now ranks first in the
island’s agricultural industry.” During the Spanish
occupation, in 1856, Governor Felipe de la Corte speculated that
cycads were “… the origins of the country’s
endemic illnesses which have become hereditary, often causing
premature aging and short life.” The unusual prevalence
of a “hereditary paralysis” among Chamorros was first
reported in the medical literature in early 1900, though it is
only after World War II that military physicians assigned to Guam
identified the diseases as ALS. Second, the reported decline in
the incidence of ALS-PDC in the 1980s was later found to be biased
because of an overestimation of the Chamorro population in the
1980s. Analysis of more current census revealed that the incidence
of ALS-PDC in Guam still remains relatively high.
But aside from all this discussion, the most compelling piece
of information is that BMAA as found in cycad flour or in a much
lesser concentration in some blue-green algae, is not toxic. BMAA
is a relatively weak compound, much weaker than common compounds
like monosodium glutamate and aspartame that are ubiquitous in
the American diet. Consumption of BMAA has never been linked to
symptoms resembling ALS-PDC, and signs of toxicity were only observed
when extremely large amounts of BMAA were fed to animals (only
one study). The amount of BMAA found to trigger “apathy,
signs of changes in the normal diurnal pattern of vigilance, periods
of immobility with expressionless face and blank stare, and a
crouched posture” were 100 to 350 mg/kg. For a normal man
of 50 kg, this is equivalent to approximately 12.5 grams of BMAA.
Numbers can, at times, be misleading. To put things in perspectives,
for the sake of comparison, how would you feel if you were to
consume 12.5 grams of, let’s say, caffeine… the equivalent
of 160 cups of coffee? Or 12.5 grams of a common sleeping pill
like Xanax… more specifically 12,500 pills of Xanax? Interesting
dose of reality, isn’t it. BMAA cannot be the cause of ALS-PDC
or Alzheimer’s disease, and the amount of BMAA reported
in some species of blue-green algae is safer than a cup of coffee.
Cause of ALS-PDC?
What then if BMAA is not the cause of ALS-PDC in Guam? The answer
is not simple, as ALS-PDC in Guam appears to be linked to a set
of environmental factors unique to Guam. Another toxin recently
isolated from cycad seeds, ß-sitosterol ß-D-glucoside
(BSSG), was shown to trigger symptoms similar to ALS-PDC. The
distribution of the disease appears to match well the presence
of BSSG; areas with the highest concentration of BSSG also have
the highest incidence of ALS-PDC.
Independently, water testing has revealed that in many areas
of Guam, particularly those areas with high incidence of ALS-PDC,
the drinking water is deficient in calcium and magnesium, and
high in aluminum. Feeding animals with such water led to neurological
problems similar to ALS-PDC. Proponent of this theory argue that
the recent decline in the disease incidence is due to decreased
isolation of the Chamorro people and population movement, acculturation
and westernization of traditional daily life.
Conclusion
The link between Alzheimer’s disease and exposure to excitotoxins
is definitely legitimate, but the proposal that BMAA present in
some blue-green algae could be the cause of Alzheimer’s
disease in North America does not pass muster. The concentrations
of BMAA found in some blue-green algae are simply far too low
to cause any problems. A much more probable cause is the widespread
consumption of other excitotoxins like glutamate and aspartame.
A single dose of 250 mg/kg of glutamate was shown to trigger brain
lesions. This means that consumption of 2.5 grams of glutamate
by a 10 kg (22 lbs) child would lead to brain lesions… merely
two common cans of soup containing on average 1.3 grams of glutamate…
also called natural flavoring or isolated proteins. When have
you heard about this in the news? When will reporters look for
the real problems?
1 Excitotoxins are products that stimulate
neurons in the brain in a manner that causes neuronal damage.
2 NMDA stand for N-methyl-D-aspartate, a compound that specifically
stimulates brain receptors for the neurotransmitter glutamate.
© Christian Drapeau
See
Printable PDF version
| 
