More Evidence Links Mediterranean Diet to Less Depression

Pauline Anderson

September 28, 2018

Adherence to a healthy diet, particularly the plant-rich Mediterranean diet, and avoidance of sugary processed foods that promote inflammation are associated with a reduced risk for depression, a new systematic review and meta-analysis suggest.

Dr Camille Lassale

This is yet more confirmation that a healthy diet not only improves physical health but also mental health, lead author Camille Lassale, PhD, research associate, Department of Epidemiology and Public Health, University College London, United Kingdom, told Medscape Medical News.

For mental health professionals, these new results provide additional support for advising patients to follow a healthier diet, added Lassale.

"A bad or unhealthy diet is responsible for so many other diseases, so you can't go wrong by advising patients to reduce processed foods and try to incorporate more fruits and vegetables into the diet," she said.

The findings were published online September 26 in Molecular Psychiatry.

"Compelling Evidence"

After searching the literature for relevant English language studies that investigated the influence of diet on depression, the researchers included 41 studies in their review. Most of the studies enrolled generally healthy participants.

Of these studies, 20 had longitudinal and 21 had cross-sectional designs. Of the longitudinal studies, the investigators included only those that had "a decent level of adjustment" to account for lifestyle factors that could affect depression, such as smoking, physical inactivity, and high body mass index, said Lassale.

The analysis compared a wide range of a priori dietary scores. Some studies included more than one such index.

Ten analyses used the Mediterranean Diet Score (MDS), seven the Healthy Eating Index (HEI) or the Alternative Healthy Eating Index (AHEI), four the Dietary Approaches to Stop Hypertension (DASH) diet score, nine the Dietary Inflammatory Index (DII), and 15 used a variety of other scores.

The MDS includes nine items: five deemed beneficial (fruit, vegetable, legumes, cereals, fish), two deemed detrimental (meat, dairy), one on dietary fat, and one on moderate alcohol intake.

The three cross-sectional studies that examined the Mediterranean diet yielded inconsistent results. However, results from four longitudinal studies showed that for people in the highest category of adherence to the diet, risk for incident depressive outcomes were lower (overall odds ratio [OR], 0.67; 95% confidence interval [CI], 0.55 - 0.82) compared with those who had the lowest degree of adherence.

The Mediterranean diet provided "the most compelling evidence" for the impact of diet on depression, said Lassale. She added that it is also "the most studied."

Striking Associations

The other index that had a "striking association with depression" was the DII, Lassale reported. This index quantifies the overall effect of diet on inflammatory potential using 45 parameters.

The studies that used this index were "a bit trickier to interpret" because the DII score is based not only on foods but also on inflammatory factors, such as C-reactive protein, polyphenols, and inflammatory cytokines, said Lassale.

She noted that many of the foods included in the Mediterranean diet (eg, oily fish, fruits, vegetables, nuts, legumes, and other plant-based nonprocessed foods) are anti-inflammatory.

Lassale added that proinflammatory foods include those that are high in trans fat, saturated fat, refined sugar, and "everything that is overly processed."

Five cohort studies and four cross-sectional studies used the DII.

Comparing the least inflammatory with the most inflammatory diet, there was a combined inverse association with depression in both longitudinal (overall OR, 0.76; 95% CI, 0.63 - 0.92) and cross-sectional (overall OR, 0.64; 95% CI, 0.45 - 0.91) studies.

"We see that the less likely you are to follow the proinflammatory diet, the less likely you are to be depressed or to develop depression," said Lassale.

Similar Trend

The analysis showed the same general trend for indices that assessed adherence to American dietary guidelines, using the HEI and the similar AHEI. These guidelines emphasize fruits and vegetables, but not the complete elimination of meat and dairy.

The three longitudinal studies showed a lower risk for incident depression for high vs low diet scores on the HEI/AHEI (OR 0.76; 95% CI, 0.57 - 1.02). However, the authors note that "this association is only borderline significant at the conventional level." They also point out that there was large degree of heterogeneity in the estimates of these three studies.

Overall, the cross-sectional studies showed an inverse association between some versions of the HEI or the AHEI and prevalence of depression (OR, 0.53; 95% CI, 0.38 - 0.75), with no apparent heterogeneity.

In addition, four studies used the DASH diet score or a modified version of it. This score has eight components. Negative components include sweet beverages, meat, and sodium; and positive components include fruit, vegetables, legumes and nuts, whole grains, and low-fat dairy products.

The DASH index was "the least consistent," said Lassale. "Mostly, there was no association between the DASH diet and depression."

In the only longitudinal study, investigators found a significantly negative association with depression incidence (OR, 0.63) only when using a particular DASH scoring system. The other DASH scores were not associated with clinical depression.

Also, results from cross-sectional studies revealed no association except for a study of adolescent Iranian girls. It showed an inverse association between DASH and depressive symptoms (OR, 0.47).

Lassale speculated that this general lack of association may be due to the fact that, although dairy food and meat are considered "detrimental" in the Mediterranean diet, the DASH diet is "not about avoiding these foods but rather finding low-fat options for them."

The DASH diet has been studied and recommended for its utility in reducing blood pressure.

Biological Mechanisms

Several biological mechanisms might explain the relationship between diet and depression, Lassale said.

One is that plant-based, unrefined foods that are rich in fiber, B vitamins, and polyphenols have an anti-inflammatory quality and may have a direct impact on brain functioning, brain structure, and neurotransmitters.

"There is a strong inflammatory cause of depression," noted Lassale. "We find that people with depression have higher levels of C-reactive protein and other markers of inflammation."

Many of the foods in the Mediterranean diet are rich in omega-3 polyunsaturated fatty acids, which not only are anti-inflammatory but may also reduce oxidative stress, she said. "They can have direct effects on the plasticity of brain cells."

Another possible route by which diet may affect mood is the microbiome-gut-brain axis. Healthy foods could modulate the relationship between bacteria in the gut and the brain, said Lassale.

She noted that this mechanism is gaining interest among researchers studying depression.

Confirming Evidence?

Lassale noted that the new analysis summarizes the increasing research on diet and depression. "Over the last few years, people have started thinking that there's definitely compelling evidence, and we just now confirmed it."

Although the cross-sectional studies "have some value," the direction of the relationship "is unclear." The new meta-analysis also included longitudinal studies in which the relationship is clearer, she added.

"With this new analysis, we show there is quite good evidence out there not only from cross-sectional but also from longitudinal studies that there is a relationship between a healthy diet and depression, and that paves the way to start clinical trials," Lassale said.

Some such trials have already been done. One of the coauthors of this new analysis, Felice Jacka, PhD, Deakin University, Food and Mood Center, Geelong, Australia, helped conduct the SMILES trial. Findings published last year showed that patients with depression who followed the Mediterranean diet for 12 weeks improved significantly more than those who received social support.

"It was the first clinical trial showing very good, encouraging results — but we need more research," said Lassale.

Once more such trials are completed, experts can perhaps develop dietary guidelines for mental health care professionals, she added.

Reinforcing and Reassuring

Asked for comment by Medscape Medical News, Drew Ramsey, MD, associate professor of psychiatry, Columbia University, New York City, said the new findings "are reassuring in the sense that they are consistent" with prior research.

"They reinforce the idea that food is a tool that we can use to improve our health, including our mental health," he said.

Ramsey, who was not involved with this research, founded the Brain Food Clinic, has written a number of popular books on nutrition and mental health, and launched the Eat to Beat Depression e-course.

"Asking about nutrition in a clinical setting has always been common sense, and now it's evidence-based common sense," he said.

However, it leaves the field wondering how to use the mounting evidence that nutrition plays a key role in mental health, he added.

"Does this mean that psychiatrists need to screen patients and refer them to coaches or nutritionists or dieticians? Does this mean that we should expect that part of a psychiatric evaluation is a nutritional evaluation?" he asked.

Ramsey said he recognizes that a healthy diet is not the entire answer to depression. But the results of this new review "mirror what we have been seeing, which is that nutrition is a piece of the puzzle; for most patients, it isn't the whole puzzle."

Laurel Cherian, MD, from the Department of Neurological Sciences, Rush University Medical Center, Chicago, also commented on the findings.

"This study was interesting in that it included longitudinal studies and also examined a variety of healthy diet patterns," Cherian told Medscape Medical News.

"One of the limitations is that there was considerable heterogeneity between studies with regard to how depression was defined and how diet quality was compared (tertiles, quintiles, etc)," she noted.

"Nonetheless, this study builds on a growing body of evidence that suggests diet could be part of a comprehensive approach to treating and preventing depression," she concluded. "Medications, therapy, and exercise are also beneficial, and people may see the greatest benefit when they use a combination of these approaches. This study further strengthens the argument for a diet intervention trial for depression."

Dr Lassale, Dr Ramsey, and Dr Cherian have reported no relevant financial relationships.

Mol Psychiatry. Published online September 26, 2018. Full text

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