VIENNA – A dietary supplement blend virtually eliminated postpartum blues in a promising proof-of-concept controlled trial, Yekta Dowlati, PhD, reported during the annual congress of the European College of Neuropsychopharmacology.
The nutraceutical cocktail is designed to compensate for the effects of the early postpartum surge in monoamine oxidase A (MAO-A) activity that her research group previously has reported. They found that as estrogen levels plunge by 100-fold in the first 3 days postpartum, brain MAO-A levels rise by 40% in affect-controlling regions, including the prefrontal cortex and anterior cingulate cortex (Arch Gen Psychiatry. 2010 May;67[5]:468-74).
That suggests a potential causal relationship with postpartum blues, since MAO-A is an enzyme whose effects include promotion of oxidative stress, apoptosis, and metabolizing serotonin, norepinephrine, and dopamine, explained Dr. Dowlati of the department of psychiatry at the University of Toronto.
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Postpartum blues is a common prodrome for postpartum depression, the most frequent complication of childbearing, which has an estimated incidence of 13%. Severe postpartum blues is a strong predictor of subsequent postpartum depression. Yet, despite the large burden of illness imposed by postpartum depression, there is no proven preventive strategy. The hypothesis being pursued in developing this nutraceutical is that a safe dietary intervention that prevents postpartum blues also may prevent postpartum depression.
The nutraceutical cocktail developed by Dr. Dowlati and her coinvestigators consists of monoamine precursors: 2 g of tryptophan, 10 g of tyrosine, and blueberry juice plus blueberry extract.
She reported on 41 healthy breast-feeding mothers who on day 5 postpartum, when postpartum blues typically peaks, were assigned to drink the dietary supplement or not. Later that day, they underwent a quantified assessment of their severity of postpartum blues based upon change from baseline in depressed mood scores on a 0-100 visual analog scale after undergoing a standardized sad mood induction procedure. This is a simple protocol widely used by psychiatrists and psychologists researching the neurobiology of mood states. Dr. Dowlati and her colleagues used the Velten protocol, in which subjects read depressing sentences while listening to sad music.
Mean scores on the Visual Analog Scale for sadness following the standardized mood induction procedure jumped by 43.8 points in the control group but were unchanged, with a mere 0.5-point increase, in the 21 women in the active treatment arm.
“The results of the present study, albeit in an open-label trial, reflect by far the most robust effects of a dietary supplement ever seen on postpartum blues. Our effect size was 2.9. Previous trials have reported effect sizes of 0.07-0.28,” she noted.
An effect size of 2.9 means that if a postpartum woman did not experience a plunge in mood after the induction protocol, there was statistically a 98%-99% chance that she had consumed the supplement.
“One explanation to account for an active effect is that the supplement is compensating for the effects of monoamine metabolism and increased oxidative stress by elevated postpartum MAO-A levels,” according to Dr. Dowlati. “Given the effect size of 2.9 and minimal effects of tryptophan and tyrosine supplementation on total levels in breast milk, there is excellent reason to pursue this supplement in a randomized, double-blind, placebo-controlled trial to further assess its effects.”
Before conducting this efficacy study, the investigators evaluated the safety of their planned intervention by randomizing 54 healthy breast-feeding women to single larger doses of oral tyrosine or tryptophan than were used in the nutraceutical cocktail or to no supplements. They found no subsequent increase in total tyrosine or total tryptophan levels in the subjects’ breast milk, although dose-dependent increases were found in free tyrosine and free tryptophan in maternal plasma. Free tyrosine was increased in breast milk; however, the level was significantly lower than what the investigators found in laboratory analysis of a dozen popular brands of infant formula.
The safety and open-label efficacy studies were funded by the Canadian Institutes of Health Research, the Ontario Mental Health Foundation, and university research grants. Dr. Dowlati reported having no financial conflicts of interest.