Could blueberries be used to relieve the symptoms of post-traumatic stress disorder (PTSD)? While this is far from an obvious line of enquiry, it has recently come under scrutiny, giving weight to the idea that blueberries may have important pharmacological properties.
Dr Joseph Francis, a professor of veterinary medicine at Louisiana State University's School of Veterinary Medicine, has been exploring the potential of blueberries for several years. His latest series of studies, conducted on rats, found that the berry successfully alleviated some of the problems associated with PTSD - or at least, the closest animal equivalent.
Having found a way to instil PTSD-type symptoms in rats, his team fed some of the animals a diet rich in blueberries, and discovered a notable change in their biochemistry. After being traumatised, their expression of the gene SKA2 was far lower than is found in normal laboratory rats (a finding that has also been noted in humans). But following the blueberry-heavy diet, their expression of this gene increased.
An earlier study by the team, released last year, found an additional benefit: the blueberry-fed rats also showed an increase in serotonin, a neurotransmitter associated with feelings of wellbeing.
"We found that in the PTSD animals there was an increase in oxidative stress and inflammation in the brain. Since blueberries are known to reduce oxidative stress and inflammation, we wanted to see whether feeding blueberries would protect these animals against this oxidative stress and whether it would have any effect on neurotransmitters," says Dr Francis, whose team presented their findings at this year's Experimental Biology Conference in April.
While Francis started out in neuroimmunoendocrinology - essentially, looking at how the nervous system and the immune system interact - he became interested in PTSD when Carl Brad Wilson, a major from the US Air Force, began a PhD in his lab. PTSD is common throughout the US population, affecting an estimated 6.8% of people in their lifetimes, but it is particularly prevalent among conflict veterans, making it a pertinent research subject.
Wilson used an animal model designed to match the behavioural, psychological and physiological elements of human PTSD. Rats were individually isolated in cylindrical containers, which had cat food smeared on the outside, before being placed in a cage with a cat for an hour. This traumatising event was repeated ten days later. Alongside the predator exposure, the rats were subjected to psychosocial stress by changing their cage mate daily. The stress regimen continued for 31 days before the rats were euthanised and their brains and blood examined.
Compared to the control group, the traumatised rats showed a decreased serotonin concentration in the brain as well as lower expression of SKA2 in the hippocampus and prefrontal cortex. This provided a useful model for studying the biochemistry of PTSD.
"This gene shuttles the stress hormone receptors to the cell membranes," says Francis. "When there's a decrease in the gene, this may not happen, so you'll have a higher concentration of stress hormone - cortisol or corticosterol - in your bloodstream."
When a traumatised group of rats were given blueberries - the equivalent of about two cups per day for a person - their corticosterol levels dropped significantly. The team found that this effect persisted well past the end of the dietary regimen.
Pending funding, Francis hopes to start a clinical trial in humans. The idea will be to take a group of patients suffering from PTSD, and to give them two cups of blueberries a day for an eight to twelve week period. Following a baseline assessment, their sleep quality and psychological function will be monitored, and blood samples will be taken to test for certain biomarkers.
This will build on an earlier trial, which found that blueberries can modulate immune response in patients with metabolic syndrome. Francis feels that these wide-ranging benefits stem from a similar mechanism.
"All chronic diseases are related to oxidative stress - oxidative stress is going to induce inflammation and inflammation is going to induce oxidative stress, so there's a vicious cycle," he explains. "Blueberries are a major antioxidant, so you're reducing the oxidative stress and preventing macrophages from infiltrating the tissues."
Resisting the hype
Francis' work is far from the first to evince these benefits. Widely dubbed a 'superfood', the blueberry is rich in various antioxidant plant compounds, with a single serving containing as many antioxidants as five servings of other fruit and vegetables. These have variously been shown to inhibit the growth of cancerous human colon cells, to reverse age-related memory decline in rats and prevent infectious bacteria from clinging to the wall of the gut.
However, it is important to differentiate marketing hype from truly well-established evidence. As the NHS Livewell website points out, there is 'very little evidence that blueberries can help protect against cancer', studies into memory 'have relied on small sample groups or animals', and the 'evidence is inconclusive' regarding high blood pressure and heart health. Larger human trials are needed before anything can be said with any surety.
Moreover, Francis cautions that the blueberry's health properties are unlikely to translate easily into a pill. As many studies have demonstrated, a single micronutrient taken out of context may act differently from a naturally occurring micronutrient in a food: its benefits are more likely to be a function of how the various chemical components interact.
"We have conducted studies where we extracted flavanols and a few other compounds from the blueberries, but we found that it didn't work," says Francis. "People want to make everything into a capsule, but it's important to note that when you extract a compound from blueberries, the compound is going through a harsh chemical process and some of the bonds are broken in the process, so the beneficial effect might be lost."
His findings should therefore be taken with a caveat: while blueberries may improve certain biomarkers of trauma in rats, this doesn't necessarily mean we'll soon have a new wonder drug for PTSD. Of course, that isn't to say that blueberry lovers should be deterred.
"It's important to note that these are rat studies," says Francis. "However, what we can say for now is that blueberries cannot hurt."