Probiotic Supplementation in Pregnancy Reduces the Risk of Anxiety and Depression

Though the evidence of the role of diet and the gut in the development of psychological disorders is established and growing, the majority of the research has either been epidemiological (observations of large groups of people – these do not show causality) or animals trials (show the mechanisms but might not completely translate to humans). At the end of all of these papers the authors remark that more high-quality human trials are required to draw firmer conclusions. Earlier in the year we had the publication of the SMILES Trial, a study that showed a cause and effect relationship between poor diet and depression and now a new paper provides more good evidence of the role of probiotics and the gut microbiome on mental health. Even more interesting is that this was not even the main aim of the research.

Researchers in New Zealand set up a trial to see whether giving pregnant women probiotics would affect their children’s risk of developing eczema. Eczema is an inflammatory skin condition and the gut microbiome plays an essential role in regulating inflammation. A baby’s gut microbiome is seeded at birth during its transit through the birth canal, or from skin contact after delivery by caesarean section. In the study 423 pregnant women were randomly assigned to two groups. One group received a daily supplement of a strain of bacteria called Lactobacillus rhamnosus (HN001). The other group received an identical looking/tasting placebo. The women took the supplement/placebo from the moment they enrolled until their child was born, and from birth until 6 months if the mother was breastfeeding. Information about the women’s mental state was taken at baseline (14-16 weeks pregnant), when the child was 6 months and 12 months old. They found a strong effect of the probiotic. The women who had taken the supplement (and none of the women knew whether they were taking the active supplement or the placebo) were much less likely to experience depression and anxiety after the birth of their children.  

The researchers report that between 10%-15% of women experience post-partum (post-natal) depression, which can impair the development of a strong bond between mother and infant, creating psychological and physical health risks for both. Medication options for breastfeeding women are limited because of the risk that the medication would be ingested by the baby in breast milk. In addition, it is practically difficult for women to access psychological or psychosocial interventions on top of the demands of a new baby. Further, some women feel reluctant to ask for help because they feel ashamed or guilty that they should feel so unhappy following the birth of their baby. Clearly then, the development of accessible and effective treatments is essential. There are many questions still to be answered about what a probiotic treatment might look like. This trial looked at only one strain and it might be that others of a combination are important too. We also need to know how long treatment should last and what the dose should be. But this well-designed study adds to the evidence of the role and importance of gut health in mental health and of taking the health of the whole body in to consideration when looking to treat mental health problems.

Reference

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial. DOI: 10.1016/j.ebiom.2017.09.013

Dietary Intervention for Depression – The SMILES Trial

I have reported on epidemiological studies that show a relationship between a consistently healthy diet and depression in the general population and in women. This research has been correlational; it shows that there is a relationship but cannot say that what causes what. It could be that depressed people are more likely to eat a poor diet. All that changed recently with the publication of a randomised controlled trial of the use of diet as a treatment of depression; The ‘SMILES’ Trial.

The 67 participants in this 12-week Australian study were depressed adults who had a clinically defined poor diet. A poor diet was one that was low in fibre, fruit and vegetables and lean protein, and high in sweets, salty snack foods and processed meats. Some participants were receiving treatment in the form of medication, talking therapy or both.

Participants were randomly assigned to either a nutritional intervention group or a befriending control group. In the intervention group the participants had seven one-hour sessions with a registered nutritionist who provided them with personalised nutritional advice, meal plans, and coached them around goal setting and motivation to help them to stick to the nutritional recommendations. They were encouraged to eat (servings in brackets):

• Whole grains (5–8 servings per day)
• Vegetables (6 per day);
•  Fruit (3 per day),
• Legumes/beans (3–4 per week);
• Low-fat and unsweetened dairy foods (2–3 per day);
• Raw and unsalted nuts (1 per day);
• Fish (at least 2 per week);
• Lean red meats (3–4 per week);
• Chicken (2–3 per week);
• Eggs (up to 6 per week); and
• Olive oil (3 tablespoons per day).

In addition, participants were encouraged to reduce their intake of “‘extras’ foods, such as sweets, refined cereals, fried food, fast-food, processed meats and sugary drinks (no more than 3 per week). Red or white wine consumption beyond 2 standard drinks per day and all other alcohol (e.g. spirits, beer) were included within the ‘extras’ food group. Individuals were advised to select red wine preferably and only drink with meals.” Those in the social support/befriending group had seven one-hour meetings with a trained professional who talked to them about neutral. Anxiety, depression and general mood were assessed at the beginning and end of the study, along with biometric and anthropometric data such as weight, waist circumference, fasting blood glucose and cholesterol.

People in the dietary intervention group were four times more likely to be in remission at the end of 12 weeks than those in the befriending group. They also had reduced severity of anxiety symptoms. There was no change in BMI, blood glucose, cholesterol or physical activity within or between the groups.

The NNT in the SMILES Trial was four. This compares favourably to common antidepressant medication which can vary from 5-16, which is still considered effective particularly in relation to the high global rates of depression. The authors also make the point that that this nutritional intervention would also have positive outcomes for other problems that are commonly associated with depression such as heart disease, type 2 diabetes and obesity. Crucially, the researchers also looked at the affordability of the diet and found that, on average, people adhering to the diet spent $26 less per week on food and drink than they were at the start of the study.

Of course, this was a small study and it will both interesting and exciting to see the trial replicated with more participants from different ethnic backgrounds. However, it is also, I think, hugely important. It is the first study that demonstrates a direct influence of diet on depression. Depressed people who improved their diet felt better. The upshot is that improving diet in line with general guidelines had a significantly positive effect on depression. The benefit of this kind of intervention is that there are no waiting lists or side-effects, and it doesn’t have to be expensive. We eat several times a day and this research shows us that each meal provides us with a valuable opportunity to make a difference to how we feel.

Jacka, F. N., O’Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., Castle, D., Dash, S., Mihalopoulos, C., Chatterton, M. L., Brazionis, M., Dean, O.M. Hodge, A. M. & Berk, M. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the “SMILES” trial). BMC Medicine, 15, 23. http://doi.org/10.1186/s12916-017-0791-y

Poor Diet Associated with Increased Risk of Depression in Women

The Whitehall II Study is a large, longitudinal study following the health and wellness of over 10,000 British civil servants between the ages of 35 and 80. Recruitment started in 1985 and follow-up is ongoing. Whilst the study primarily releases data on the relationship between physical health and socioeconomic status the enormous amount of data collected is often shared with and analysed by international researchers interested in other aspects of health and lifestyle. A paper published in Clinical Psychological Science reviewed the Whitehall data looking at the relationship between diet and depression. They were curious as to whether the inflammatory potential of a person’s diet had any bearing on their risk of developing the illness.

Inflammation is they way that the body responds to physical illness and injury and is also associated with lifestyle factors such as chronic stress and poor diet. The Dietary Inflammatory Index (DII) is a reliable assessment of how likely certain foods are to promote inflammation in the body. Broadly, processed foods increase inflammation while whole foods, fruits, vegetables, nuts and oily fish reduce it. A higher score on the DII is linked to higher markers of inflammation in the body.

In this analysis the researchers looked at the available dietary information and depression status of 4246 people over a period of five years. They were interested in what they have called ‘recurrent depression’ - people who had depression at the start and again at the end of this five-year period. (They did not look at whether the depression was ongoing during this period or whether it had gone in to remission at any point.) Alongside diet they looked at other health-related factors such as level of exercise, smoking status, alcohol consumption, obesity, heart disease, diabetes and stroke. 

The researchers found that women with high scores on the Dietary Inflammatory Index were significantly much more likely to develop recurrent depression, and this effect was independent of other health factors. This is similar to the results of the large Spanish 'SUN Project' that showed that healthy (anti-inflammatory) diets were linked to a reduced risk of depression in men and women. The authors comment that these results support the growing body of research in to the relationship between diet, inflammation and depression. 

Reference

Akbaraly, T. N., Kerlau, C., Wyart, M., Chevallier, N., Ndiaye, L., Schivappa, N., Hébert, J. R., Kivimäki, M. (2016). Dietary Inflammatory Index and Recurrence of Depressive Symptoms: Results From the Whitehall II Study. Clinical Psychological Science, first published on August 8, 2016 doi:10.1177/2167702616645777

Dietary Fibre Linked with Improved Cognitive Control in Children

A correlation study conducted with small group of 7 and 9 year olds demonstrated a positive relationship between diet quality, in particular dietary fibre content, and performance on a task designed to assess attention and the ability to disregard distracting stimuli.

65 children undertook a modified version of the Erikson Flanker Test in which they were asked to pay attention to the direction of a fish in the centre of a computer screen and to try to ignore other fish that appeared on the screen at the same time that were facing either the same direction or the opposite direction of the target fish. Their results were correlated against food diaries that tracked a range of nutrients and subsets of nutrients. For example fats were broken down in to saturated fatty acids, cholesterol, omega-3s and DHA .

They found that children who had higher fibre diets had significantly improved accuracy scores on the Flanker test. The results showed that soluble fibre was associated with overall accuracy and pectin was particularly linked to accuracy in the version of the test that required greater effort. The researchers postulate that the effects might be linked to better control of blood sugar and/or the interaction of the gut microbiota. Fibre cannot be assimilated into the body but is highly fermentable by the bacteria in the gut. Some of the important end products of this fermentation are short-chain fatty acids, which have been linked to reduced inflammation in the brain and increased BDNF, compound associated with the creation of new brain cells.

Whilst this study was conducted on children it is highly likely that the outcomes will be similar in adults.

• High soluble fibre foods: Oats and oat bran, beans, lentils, apples, pears.
• High insoluble fibre foods: Wheat bran and wholegrains, brown rice, seeds, fruit and vegetable skins.
• High pectin foods: Apples, pears, quince, peaches, plums, oranges, lemons, grapefruit, gooseberries, apricots, guava, carrots, tomatoes.

Reference

Khan, N. A., Raine, L. B., Drollette, E. S., Scudder, M. R., Kramer, A. F., & Hillman, C. H. (2015). Dietary Fiber Is Positively Associated with Cognitive Control among Prepubertal Children. The Journal of Nutrition, 145(1), 143–149. http://doi.org/10.3945/jn.114.198457

Healthy Diet Linked to Reduced Risk of Depression

In 2015 a large Spanish study reported results showing that improvements in diet reduced a person's likelihood of developing depression. Similarly, a new correlation study of Iranian adults (average age 36 years) has demonstrated a statistically significant relationship between healthy diet and reduced rates of depression. The researchers assessed the diet and lifestyle of over 3000 people - looking at their eating habits, weight, BMI, smoking status and levels of psychological distress - and compared them against measures for anxiety and depression. They found that non-smokers were less likely to be anxious than smokers and those with healthier diets were 29% less inclined to be depressed than those with poor diets. Further research is required to understand the predictive features of these results.

Saneei, P., Esmaillzadeh, A., Keshteli, A. H., Reza Roohafza, H., Afshar, H., Feizi, A. & Adibi, P. (2016). Combined healthy lifestyle is inversely associated with psychological disorders in adults. PLoS One. DOI: 10.1371/journal.pone.0146888

Healthy Diets Reduce Risk of Depression

A large (15,000 participants) Spanish study has shown that diets high in nutrients are linked to a reduced risk of depression. This study has generated a lot of interest not only because of the large cohort size, which makes the results more generalisable, but because it is thought to be the first to follow healthy individuals and track, over 10 years, those who went on to develop illness and disease.

The researchers looked at three diets:

• Mediterranean Diet – characterised by the consumption of vegetables, legumes, fruits and nuts, cereals, fish and seafood; low intake of meat and dairy products, and moderate alcohol intake.

• Vegetarian Dietary Pattern – a kind of ‘flexitarian’ diet that promotes eating plant foods (including potatoes) most of the time but allowing for a little meat

• Healthy Eating Index- promotes eating larger amounts of vegetables, fruits, whole-grain bread, nuts, beans and pulses, omega 3s and unsaturated fats, and smaller amounts of sugar-sweetened beverages and fruit juice, red/processed meat, trans fats, and alcohol.

As part of the study the researchers also looked at activity levels, BMI, health history and vitamin supplementation, and the analysis was controlled for a number of variables including age, sex and smoking status.

For the statistical analysis the levels of adherence were split in to five groups (quintiles). So on a scale of 1-5, those in group 1 ate the least healthy diets while those in group 5 were paragons of healthy eating. The results showed that those in groups 2-5 had a 25-30% reduced risk of developing depression than those in group 1. Interestingly, there was a plateau in this effect once the respondents had moderately good diets. The researchers believed this to be due to a threshold effect; once you are consuming adequate amounts of a nutrient there is no additional benefit of consuming larger quantities of it.

The researches did not highlight any individual food or nutrient as being particularly important or protective. In fact they pointed out in their discussion the inconclusive results from other studies that looked at the relationship between individual nutrients (vitamins, minerals or fats) and depression. However, this and other studies have demonstrated the strong relationship between the quality of the overall diet and risk of depression. It is likely that it is the interaction of different compounds from various foods that offers most protection not just to depression but to overall health. 

Reference

Sánchez-Villegas, A., Henríquez-Sánchez, P., Ruiz-Canela, M., Lahortiga, F., Molero, P., Toledo, E., & Martínez-González, M. (2015). A longitudinal analysis of diet quality scores and the risk of incident depression in the SUN Project. BMC Medicine, 13, 197-197.