It’s better known to us for its use in batteries, but could lithium – also found in drinking water, cabbages, wholegrains and potatoes – help to protect against dementia?
This is the suggestion behind several recent studies investigating whether this light metal – used for decades at high doses to treat depression and bipolar disorder – could play a role in brain health, albeit in much lower doses.
Lithium occurs naturally in minerals and rocks and enters the soil, rivers and lakes after being dissolved in rainwater.
As a result, it’s naturally present in some foods and water in very small amounts.
It is not considered an essential nutrient and there is no officially recommended daily intake (although some researchers have proposed a provisional amount of 1mg daily for a 70kg adult). However, it’s long been used in the form of lithium carbonate for treatment- resistant depression and manic bipolar episodes.
As Dr Thomas MacLaren, a consultant psychiatrist at the Chelsea and Westminster Hospital in London, explains: ‘Lithium can lower levels of the energy-boosting chemical dopamine involved in manic episodes, while enhancing activity of the GABA receptors [which calm the nervous system by damping down signalling].’
But brain-protective qualities are also emerging. Dr Ivan Koychev, an NHS consultant neuropsychiatrist and a clinical associate professor in neuropsychiatry at Imperial College London, explains: ‘Lithium seems to play a role in maintaining the effectiveness with which the brain makes connections between brain cells.’
This is important because although we are born with a fixed number of brain cells, our brains continue to form new connections – or synapses – throughout our lives, a process key to learning new information and building a brain that’s more resilient to damage from diseases such as Alzheimer’s.
A clinical trial involving 40 people at Johns Hopkins University in the US is now evaluating the safety and tolerability of low-dose lithium orotate in adults with early-stage Alzheimer’s (picture posed by model)
Lithium also inhibits an enzyme, GSK-3, which converts the naturally occurring protein tau into the toxic misshapen clumps – or tangles – associated with Alzheimer’s, adds Dr Koychev.
Scientists do not yet understand exactly why Alzheimer’s develops – but one theory is that in some people increased GSK-3 activity is a driver.
It’s also thought that with age, the brain’s ability to clear out toxins weakens, which may lead to greater GSK-3 activity.
This leads to the build-up of abnormal protein clumps – or beta-amyloid plaques – which are a characteristic of the disease and thought to interfere with the brain’s ability to store and recover memories, and manage complex activities such as speech and decision making.
Several recent studies have sparked this new interest in lithium. The most striking, led by Harvard Medical School, published last year in the journal Nature, established a link between low levels of lithium in the brain and cognitive impairment – and suggested that the element might also help protect against Alzheimer’s.
The ten-year study found lower lithium levels in the post-mortem brain tissue of people with mild cognitive impairment, a potential precursor of dementia, compared with healthy people.
Interestingly, the lithium was found to be concentrated inside the amyloid plaques of those with Alzheimer’s – suggesting the plaques might ‘capture’ or ‘suck out’ the lithium, leaving less available to protect healthy brain tissue.
The study also found that restoring lithium appeared to protect or improve the memory of mice bred to have Alzheimer’s-like brain changes.
Meanwhile, mice given lower levels of lithium throughout their lives developed accelerated Alzheimer’s-like brain changes, while those with normal levels were better protected from symptoms.
Several studies have also found links between slightly raised levels of lithium in drinking water (occurring as a result of regional variation) and lower rates of dementia, says Dr MacLaren, who also works at the private Re:Cognition Health clinic in London. But a small-scale US trial involving giving low-dose lithium to older adults with mild cognitive impairment didn’t replicate the dramatic improvements seen in the Harvard mouse experiment.
Experts agree that more research into lithium is needed.
One difficulty, says Dr Koychev, is obtaining funding for large-scale trials – ‘given that any resulting drug would only cost pennies because lithium is not a patented medicine.’ A further problem is that dementia starts developing ten to 20 years before first symptoms – ‘and by this point the brain is already damaged’.
Then there is the question about which is the most suitable form of lithium to use. For instance, 1mg lithium carbonate – the type used in psychiatric medication – contains about 0.19mg lithium, while lithium orotate, used in supplements, contains about 0.04mg.
Bipolar disorder is treated with high doses – in the region of 400mg to 1.2g of lithium carbonate, says Dr Koychev.
‘We know that this is effective, but it has well-documented side-effects including nausea and tremors long term.’
It can make the kidneys less responsive to the hormone that concentrates urine, so you pass greater quantities of urine, causing thirst, dehydration and potentially reducing kidney function in some.
Dr Thomas MacLaren, a consultant psychiatrist at the Chelsea and Westminster Hospital in London, says several studies have found links between slightly raised levels of lithium in drinking water and lower rates of dementia
Also, it can block the release of thyroid hormones – leading to an underactive thyroid gland – and raise calcium levels (which may, in turn, lead to thirst, constipation, nausea and muscle weakness). Higher concentrations can affect heart function and rhythm.
The Harvard study used lithium orotate: this appeared to become less trapped than lithium carbonate in the amyloid plaque, potentially explaining why the animals’ Alzheimer’s symptoms improved. Little is known about how it behaves in humans, but a clinical trial involving 40 people at Johns Hopkins University in the US is now evaluating the safety and tolerability of low-dose lithium orotate in adults with early-stage Alzheimer’s.
Participants will receive either lithium orotate (containing 1mg lithium) or a placebo, daily for nine weeks.
Dr Koychev is a key investigator in a UK pilot study monitoring the effects of giving low-dose lithium carbonate to people at risk of Alzheimer’s – as identified by raised levels of a biomarker called pTau 217, which is linked to amyloid build-up. (It is also already used to confirm the diagnosis if people have symptoms.)
The trial aims to recruit 100 people – with half given low doses of lithium carbonate and the rest a dummy pill.
In the meantime, given lithium is available in supplement form, should we all be taking a daily tablet – typically containing 4-5mg and costing around 10p – as a preventative?
Dr MacLaren suggests those with a family history might consider it, even for a few weeks, to see if memory skills improve. But he stresses they must check with their GP. He also says a multivitamin including small amounts of lithium orotate is something he’d ‘look seriously for myself in the future’.
But Dr Koychev believes it’s too soon to recommend lithium supplements. ‘Recommendations should follow the science and we are not there yet,’ he says. ‘This is particularly true for anyone with kidney or thyroid problems – who should discuss it with their health provider first before taking lithium,’ he warns.
