In the special article and classic article last year, evidence was reviewed regarding antidepressants and suicide, and PL concluded there was little benefit if any with those agents, but there was probably a small amount of harm. Lithium, on the other hand, was shown to have clear and large benefit for suicide prevention. The current article of the April 2015 issue reviewed a meta-analysis of lithium studies which demonstrates that benefit, and readers are encouraged to revisit that article if they want to see that evidence for themselves.
In this special article, we plan to extend that prior discussion by focusing on research on very low doses of lithium in drinking water, and its apparent anti-suicide benefits.
We think about certain minerals as being essential for life: there's calcium and magnesium, which seem needed for normal heart rhythm. There's sodium and potassium, needed for cell membrane function. These are all basic ions, part of the periodic table of chemical elements. They are essential for life; but we don't think of them as toxic or dangerous. Yet, too much magnesium or potassium causes cardiac arrhythmia leading to immediate death. Too much calcium can cause delirium, and too much sodium causes swelling of the brain.
Lithium also is an essential mineral, needed for viability of life. If you have none, zero, then the organism’s ability to live is harmed. We all know too much is toxic, and so it is often seen as dangerous. Yet we don't seem to fear potassium or calcium in the same way.
All drugs are toxic; only the dosing and indication makes them therapeutic. That’s the old maxim, dating back to Paracelsus and later William Osler. But the maxim applies not just to “drugs”; it applies to the chemical elements themselves, the basic building blocks of biological life. We should say instead:
All elements of chemistry are toxic; it’s only their amount and combinations that make them therapeutic.
First, let’s appreciate that lithium is essential for life. Chemists and geologists study such matters by exposing animals to a diet deficient or wholly lacking in a certain element. They then compare those animals to others who are fed a diet rich in the element. If one group dies more quickly than the other, then the element is deemed to be essential for viability of the animal.
With lithium, this research has been conducted with worms, mice, rats, and goats. It turns out that animals deprived of any lithium have much shorter lifespans than sheep who eat the usual amount of lithium in the diet. These animal studies provide context for studies of effects of lithium in drinking water.
Lithium seeps from rocks into the ground, where it is taken up into water, or into vegetables. It is consumed by animals and humans through eating vegetables or meats of other animals who have eaten vegetables. Eggs, for instance, have a notable amount of lithium. All this depends of course on the source of such food. Since food is shipped to different parts of the world, a better measure of local lithium supply is the drinking water, which tends to come from local sources.
In the last 50 years, about ten different studies have been conducted of the biological, medical, and social effects of lithium in drinking water. To give a sense of these studies, let’s take the first from 1970, which looked at lithium levels in the 100 largest American cities. It found lower overall mortality in areas with higher lithium levels; much of this benefit was related to less death from cardiovascular disease. Another 1970 study compared different counties in Texas. More recently, a 2009 study in Japan looked at over 1 million people, and 4 reports in 2011-2012 came from Japan, England, and Austria, and a new Texas study was published in 2013. These studies mainly focus on suicide, and, rather consistently, they find lower suicide rates in those regions where lithium levels are higher in water compared to those regions with lower lithium levels.
The most obvious question in such population studies is the issue of confounding bias, as discussed in the fourth PL issue. What other factors in these populations could affect suicide rates? Could it be that the lithium association is spurious because of those other factors? ...