How diet affects mental health

A new expert review confirms that diet significantly influences mental health and wellbeing, but cautions that the evidence for many diets is comparatively weak. This, the most up to date overview of the new field of Nutritional Psychiatry, is produced, by the Nutrition Network of the ECNP and is published in the peer-reviewed journal European Neuropsychopharmacology (see download details below).
Lead author, Professor Suzanne Dickson (University of Gothenburg, Sweden) said:
"We have found that there is increasing evidence of a link between a poor diet and the worsening of mood disorders, including anxiety and depression. However, many common beliefs about the health effects of certain foods are not supported by solid evidence".
The researchers found that there are some areas where this link between diet and mental health is firmly established, such as the ability of a high fat and low carbohydrate diet (a ketogenic diet) to help children with epilepsy, and the effect of vitamin B12 deficiency on fatigue, poor memory, and depression.
They also found that there is good evidence that a Mediterranean diet, rich in vegetables and olive oil, shows mental health benefits, such as giving some protection against depression and anxiety. However, for many foods or supplements, the evidence is inconclusive, as for example with the use of vitamin D supplements, or with foods believed to be associated with ADHD or autism.
"With individual conditions, we often found very mixed evidence", said Suzanne Dickson. "With ADHD for example, we can see an increase in the quantity of refined sugar in the diet seems to increase ADHD and hyperactivity, whereas eating more fresh fruit and vegetables seems to protect against these conditions. But there are comparatively few studies, and many of them don't last long enough to show long-term effects".
The study confirms that while certain foods can be associated with a mental health condition, this tells us little about why the food causes this effect. It concludes that the need to link mental health effects with provable dietary causes needs to be the main focus of future research in nutritional psychiatry.
Professor Dickson continued:
"There is a general belief that dietary advice for mental health is based on solid scientific evidence. In reality, it is very difficult to prove that specific diets or specific dietary components contribute to mental health.
The scientists confirmed that some foods had readily provable links to mental health, for example, that nutrition in the womb and in early life can have significant effects on brain function in later life. Proving the effect of diet on mental health in the general population was more difficult.
Suzanne Dickson said "In healthy adults dietary effects on mental health are fairly small, and that makes detecting these effects difficult: it may be that dietary supplementation only works if there are deficiencies due to a poor diet. We also need to consider genetics: subtle differences in metabolism may mean that some people respond better to changes in diet that others.
There are also practical difficulties which need to be overcome in testing diets. A food is not a drug, so it needs to be tested differently to a drug. We can give someone a dummy pill to see if there is an improvement due to the placebo effect, but you can't easily give people dummy food. Nutritional psychiatry is a new field. The message of this paper is that the effects of diet on mental health are real, but that we need to be careful about jumping to conclusions on the base of provisional evidence. We need more studies on the long-term effects of everyday diets".
Commenting, the Chair of the ECNP Scientific Programme Committee, Professor Andreas Reif (University Hospital, Frankfurt am Main) said:
"The interface between gut and the brain on the one side and diet and mental health on the other side is one of the most debated issues in biological psychiatry at the moment, and is an exciting development which has gained momentum in the last decade. Many high-quality findings (mainly from animal studies) have been published in top notch journals in recent years, but this contrasts with the comparative shortage of hard evidence on how nutrition and mental health are connected in humans. This leaves room for speculation and flawed science. This comprehensive review is therefore much-needed as it sheds light on hypes and hopes, facts and fiction in the new field of Nutritional Psychiatry. As the potential societal impact of this rapidly developing field is enormous, we must be scientifically sound in making our recommendations. This review is an important and scholarly contribution".
This is an independent comment; Professor Reif was not involved in this work.

Aspirin appears to curb colorectal cancer recurrence and tumor growth, study finds

 The benefits of a daily aspirin may extend beyond heart health to colorectal cancer treatment, say City of Hope researchers who have found aspirin appears to reduce tumor growth and inhibit recurrence of the disease. The trick now, researchers say, is to determine the right dosage of aspirin that can be used as a daily prophylactic without triggering dangerous side effects such as stomach and brain bleeds.
"Some might say aspirin is a 'miracle drug' because of its potential to prevent diseases that result from chronic inflammation, such as cancer, Alzheimer's, Parkinson's and arthritis," said Ajay Goel, Ph.D., senior author of a new study and chair of the Department of Molecular Diagnostics, Therapeutics and Translational Oncology at City of Hope.
"The reason aspirin isn't currently being used to prevent these diseases is because taking too much of any anti-inflammatory eats at the stomach's mucus lining and causes gastrointestinal and other problems. We are getting closer to discovering the right amount of daily aspirin needed to treat and prevent colorectal cancer without causing scary side effects."
The study, published in the journal Carcinogenesis on Jan. 6, used mouse models and mathematical modeling to parallel the amount of daily aspirin people in the U.S. and Europe are taking in clinical trials. The City of Hope-led research found that as the aspirin doses increased, the rate of cell death increased while the division rates of cells decreased, meaning tumor cells were more likely to die and not proliferate.
"We are now working with some of the people conducting those human clinical trials to analyze data and use mathematical modeling. This process adds a layer of confidence to the findings and guides future human trial designs," Goel said, adding that colorectal cancer is among the top five cancers diagnosed every year.
Research details Goel and his colleagues tested three varying daily doses of aspirin in four colorectal cancer cell lines, including tumors with microsatellite instability and mutations in the PIK3CA gene, which has been tied to increased risk of endometrial, colon and aggressive breast cancers.
Then the researchers divided 432 mice into four groups: control, low-dose aspirin (15mg/kg), medium-dose aspirin (50mg/kg) and high-dose aspirin (100mg/kg) - the mouse equivalent of 100mg, 300mg and 600mg for humans. The tumors from three mice in each treatment group were analyzed on days three, five, seven, nine and 11.
Researchers inspected "cellular apoptosis" (programmed cell death) and found that the percentage of cells programmed to die increased in all cell lines. Exactly how much, however, depended on the amount of aspirin that was consumed, suggesting that aspirin triggers a domino effect of cell death in all colorectal cell lines regardless of genetic background.
Notably, the scientists observed that low-dose aspirin was especially effective in suppressing tumor growth in animal models that had more PIK3CA genes. The finding was significant because the mutated version of these genes has been associated with increased risk of certain cancers.
To further validate the findings, the scientists applied mathematical modeling to the experimental data. They measured the rates of cell division and cell death and used mathematical modeling to determine the probability that tumor cell colonies could survive and develop into actual tumors.
"Speaking metaphorically, they were building a hurricane model to predict the path a cyclone would take," said Russell Rockne, Ph.D., a mathematical oncology scientist at City of Hope who was not involved in the study. "Mathematics and computational biology increasingly play a larger role in basic and translational research in cancer. Mathematical oncologists like myself take data, separate it into discreet parts and use math to explain why something like aspirin could have an inhibitory effect against colorectal cancer."

American College of Physicians issues guideline for testosterone treatment in adult men

Physicians should prescribe testosterone for men with age-related low testosterone only to treat sexual dysfunction, the American College of Physicians (ACP) says in a new evidence-based clinical practice guideline published today in Annals of Internal Medicine. "Physicians are often asked by patients about low 'T' and are skeptical about the benefits of testosterone treatment," said ACP President Robert M. McLean, MD, MACP. "The evidence shows that men with age-related low testosterone may experience slight improvements in sexual and erectile function. The evidence does not support prescribing testosterone for men with concerns about energy, vitality, physical function, or cognition."
ACP's guideline, endorsed by the American Academy of Family Physicians, applies to adult men with age-related low testosterone. It does not address screening or diagnosis of hypogonadism, or monitoring of testosterone levels.
Physicians should discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual and erectile function based on the potential benefits, harms, costs, and patient preferences, ACP says. ACP also recommends that physicians reevaluate symptoms within 12 months and periodically thereafter. Physicians should discontinue testosterone treatment if sexual function does not improve, and they should not initiate testosterone treatment to improve energy, vitality, physical function, or cognition because the evidence indicates testosterone treatment is not effective.
"Given that testosterone's effects were limited to small improvements in sexual and erectile function in men with low testosterone levels, it is unlikely that screening men for low testosterone levels or treating men without sexual or erectile dysfunction and low testosterone levels would be effective." Dr. McLean said.
ACP suggests that physicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function because the costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar.
The annual cost in 2016 per beneficiary for testosterone replacement therapy was $2,135.32 for transdermal and $156.24 for the intramuscular formulation according to paid pharmaceutical claims provided in the 2016 Medicare Part D Drug Claims data.
"Most men are able to inject the intramuscular formulation at home and do not require a separate clinic or office visit for administration," said Dr. McLean.
Men experience a gradual decline in serum total testosterone levels as they age, starting in their mid-30s, at an average rate of 1.6 percent per year. This condition is referred to as age-related low testosterone. The incidence of low testosterone in the U.S. is approximately 20 percent of men over age 60 years, 30 percent over age 70, and 50 percent over age 80, though prevalence of low testosterone with sexual dysfunction symptoms (defined as at least three sexual symptoms with total testosterone less than 320 nanograms per decilitre) is lower. It is uncertain whether nonspecific signs and symptoms associated with age-related low testosterone are a consequence of age-related low testosterone levels or whether they are a result of other factors, such as chronic illnesses or medications.
ACP developed its recommendations in "Testosterone Treatment in Adult Men with Age-Related Low Testosterone" based on a systematic evidence review on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. The Minnesota Evidence-based Synthesis Center conducted the review funded by ACP. ACP's Clinical Guidelines Committee evaluated the clinical outcomes using the GRADE system for sexual function, physical function, quality of life, energy/vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events.

Mindfulness makes it easier to forget your fears

A new study shows that brief daily mindfulness training delivered through the HEADSPACE mindfulness app makes it easier to achieve lasting extinction of fear reactions

University of Southern Denmark Faculty of Health Sciences

Mindfulness has been shown to reduce negative emotions in both healthy individuals as well as patients with psychological problems. Studies have also shown that mindfulness is effective for treating clinical emotional problems like anxiety, depression, stress and trauma related disorders. The biological mechanisms that underlie these positive effects on emotional functioning are not sufficiently understood but brain imaging studies have shown that mindfulness training is associated with changes in regions of the brain previously known to be involved in extinction learning, making extinction a likely candidate. However, an actual effect of mindfulness training on extinction learning has never been demonstrated.
In a new study, researchers at University of Southern Denmark, Uppsala University, Lund University, Peking University and Icahn School of Medicine at Mount Sinai, can now show that mindfulness training facilitates extinction of conditioned fear reactions, producing lasting reductions in threat related arousal responses.
In this study, healthy subjects were randomly assigned to receive either 4 weeks of daily mindfulness training delivered through the Headspace mindfulness app, or were assigned to a wait list control condition. Subsequently, the participants underwent psychological experiments on two consecutive days in which conditioned fear reactions were established on day 1 and then immediately extinguished.
On day 2, the subjects returned and the lasting effects of extinction were evaluated.
Conditioned fear reactions were established by showing the participants neutral images on a computer screen and then some of the images were directly followed by an uncomfortable electric shock to the hand.
After a number of such pairings, the subjects showed elevated autonomic arousal responses just when viewing the pictures, demonstrating that conditioned fear reactions had been learnt.
Fear reactions were measured using skin conductance, an index for how much the subject is sweating, which is a corollary for the fight-or-flight response in humans.
Then, the researchers extinguished these reactions by repeatedly showing the images again but this time omitting the shocks.
In this way, the participants learnt that the images that previously signaled an upcoming uncomfortable shock no longer did so, and consequently subjects showed a substantial decrease in autonomic arousal when viewing the images.
After 24 hours, in order to test the retention of extinction learning, the participants returned to the lab, were hooked up to the shock apparatus and again shown the images they had viewed on the previous day, although no shocks were delivered.
This was the critical test of the study since extinction learning is normally unstable, and fear reactions typically return after a delay even when the subject has gone through successful extinction. In line with the researchers' hypotheses, the group that had been doing mindfulness training now showed lower fear reactions compared to the control group.
The fear reactions in the mindfulness group remained at the same low level they had been by the end of extinction the previous day indicating an improved ability to form and retain extinction memories, whereas the control group showed a substantial increase in fear reactions compared to extinction the previous day.
When comparing the groups reactions during conditioning and extinction on day 1, no differences could be observed, showing that the two groups learned and extinguished the conditioned fear reactions to a similar extent, and the authors conclude that mindfulness appears to have a specific effect on extinction retention.
According to the study's first author Johannes Björkstrand, the findings are interesting for a number of reasons.
- We can show that mindfulness does not only have an effect on subjective experiences of negative emotions, as has been shown previously, but that you can actual see clear effects on autonomic arousal responses, even with a limited amount of training. It is also interesting that the intervention appears to have a specific effect on extinction retention, which is in line with previous brain imaging studies on mindfulness, and also has some implications for how these types of interventions could be used to treat anxiety related problems in a clinical context.
Anxiety and trauma related disorders are often treated using exposure therapy, a psychological treatment that is based on extinction learning, but not everyone responds to these treatments. One possible explanation is that individuals with these disorders have been shown to have difficulties in forming lasting extinction memories when compared to healthy individuals, which could represent an underlying vulnerability that increases the risk of developing these types of problems to begin with and constitutes an impediment to successful treatment.
- Our results suggest, that if you combine mindfulness training with exposure therapy, maybe you can achieve larger and longer lasting treatment effects. In this way you could get at an underlying vulnerability factor and more people would respond to these treatments, but studies in clinical populations and actual treatment studies are needed before we can draw any firm conclusions in this matter, says Johannes Björkstrand.
The researchers now want to move forward and investigate the underlying neurobiological mechanisms that are involved.
- We are currently repeating the experiment with twice the number of participants, and the whole thing is carried out inside an fMRI-scanner equipped with an extra strong electromagnetic field so that we can measure their brain activity to a high degree of precision throughout all parts of the experiment. We hope to show that the effect is robust and that we can replicate the current findings, and also say what processes in the brain are involved in producing these effects. We just finished data-collection but we still have a rather large amount of analysis work to do before we arrive at any results, says senior author, associate professor Ulrich Kirk.

Processed foods highly correlated with obesity epidemic in the US

As food consumed in the U.S. becomes more and more processed, obesity may become more prevalent. Through reviewing overall trends in food, George Washington University (GW) researcher Leigh A. Frame, PhD, MHS, concluded that detailed recommendations to improve diet quality and overall nutrition are needed for consumers, who are prioritizing food that is cheaper and more convenient, but also highly processed. Her conclusions are published in a review article in Current Treatment Options in Gastroenterology.

"When comparing the U.S. diet to the diet of those who live in "blue zones" - areas with populations living to age 100 without chronic disease - the differences are stark," said Frame, co-author of the article, program director for the Integrative Medicine Programs, executive director of the Office of Integrative Medicine and Health, and assistant professor of clinical research and leadership at the GW School of Medicine and Health Sciences. "Many of the food trends we reviewed are tied directly to a fast-paced U.S. lifestyle that contributes to the obesity epidemic we are now facing."
The rising obesity epidemic in the U.S., as well as related chronic diseases, are correlated with a rise in ultra-processed food consumption. The foods most associated with weight gain include potato chips, sugar sweetened beverages, sweets and desserts, refined grains, red meats, and processed meats, while lower weight gain or even weight loss is associated with whole grains, fruits, and vegetables. Other food trends outlined in the report include insufficient dietary fiber intake, a dramatic increase in food additives like emulsifiers and gums, and a higher prevalence of obesity, particularly in women.
In mice and in vitro trials, emulsifiers, found in processed foods, have been found to alter microbiome compositions, elevate fasting blood glucose, cause hyperphagia, increase weight gain and adiposity, and induce hepatic steatosis. Recent human trials have linked ultra-processed foods to decreased satiety (fullness), increased meal eating rates (speed), worsening biochemical markers, including inflammation and cholesterol, and more weight gain. In contrast, populations with low meat, high fiber, and minimally processed foods -- the "blue zones" -- have far less chronic diseases, obesity rates, and live longer disease-free.
"Rather than solely treating the symptoms of obesity and related diseases with medication, we need to include efforts to use food as medicine," said Frame. "Chronic disease in later years is not predestined, but heavily influenced by lifestyle and diet. Decreasing obesity and chronic disease in the U.S. will require limiting processed foods and increasing intake of whole vegetables, legumes, nuts, fruits, and water. Health care providers must also emphasize lifestyle medicine, moving beyond 'a pill for an ill.' "

Blood pressure control for people aged 80 and older: What's the right target?

Journal of the American Geriatrics Society research summary

American Geriatrics Society

The number of people who are 80-years-old and older is on the rise, and will account for nearly 10 percent of the whole U.S. population by 2050. Since the lifetime chance for developing high blood pressure is at least 70 percent by age 80, more and more people will be at risk for the health problems that high blood pressure can cause.
High blood pressure, or hypertension, is sometimes called the "silent killer" because it produces few, if any, symptoms. In fact, you might not even realize you have high blood pressure. But if it's not treated, this condition can lead to heart attacks, strokes, kidney disease, and other serious problems, including a risk for dementia.
The 2017 American College of Cardiology and American Heart Association blood pressure guidelines recommend that most people aged 65 or older maintain their systolic blood pressure (the first number in a blood pressure reading) at less than 130 mmHg. But, people 80 years or older often also have multiple chronic health conditions, can be frail, take several medicines, and could have cognitive problems. Because of this, it's still unclear whether the risks and benefits of lowering systolic blood pressure to less than 130 mm Hg are the same for people aged 80 years and older as they are for people aged 65 to 80.
Given this knowledge gap, a team of researchers focused on this group of older adults within a large randomized trial called the Systolic Blood Pressure Intervention Trial (SPRINT). They published their findings in the Journal of the American Geriatrics Society. In their analysis of SPRINT data, the researchers focused on people aged 80 and older, who had reported heart disease events (such as heart attacks or strokes), changes in kidney function, cognitive impairment, quality of life, or death. The researchers also explored whether impairments in cognitive or physical function had any effect on intensive blood pressure control.
The analysis included 1,167 participants. Most were around 84 years old, and about 3 percent were 90 or older. Their baseline systolic blood pressure was around 142 mmHg. Most of the participants had at least three chronic health conditions. More than half were taking at least five medications and about 27 percent had a history of heart disease.
The participants were randomly assigned to one of two groups. One group received "intensive" treatment targeting to lower their blood pressure to less than 120 mmHg. The other group received treatment to target lowering their blood pressure to less than 140 mmHg.
The people who received treatment to lower their blood pressure to less than 120 mmHg experienced a lower risk for heart disease events, as well as less risk for mild cognitive impairment and death from all causes. However, people in this group also experienced an increased risk of small, but meaningful, declines in kidney function as well as hospitalizations for short term kidney damage (from which most people recovered). Attempting to lower systolic blood pressure to less than 120 mmHg did not increase the risk for injury-causing falls. This is important, since falls raise the risk for death in older adults and low blood pressure can result in falls.
While the rate of developing dementia was similar in the two groups, participants in the intensive 120 mmHg group were 28 percent less likely to develop mild cognitive impairment.
The researchers also reported that people with better cognitive function (remembering, thinking, and making decisions) at the beginning of the study benefited the most from intensive blood pressure control. They also experienced less heart disease and fewer deaths. This same benefit was not seen in participants who had poorer cognitive function at the beginning of the study. However, there was not strong evidence of intensive blood pressure control having a harmful impact on death rates or developing heart disease for those with poorer cognitive function.
The researchers concluded that, for adults aged 80 years or older, intensively controlling systolic blood pressure to less than 120 mmHg lowers the risk of heart attacks, stroke, death, and mild cognitive impairment, but increases the risk of declines in kidney function. Benefits related to the risk for heart disease and death were highest in people with higher cognitive performance at the beginning of the trial.

Keep exercising: New study finds it's good for your brain's gray matter

Cardiorespiratory exercise -- walking briskly, running, biking and just about any other exercise that gets your heart pumping -- is good for your body, but can it also slow cognitive changes in your brain?
A study in Mayo Clinic Proceedings from the German Center for Neurodegenerative Diseases provides new evidence of an association between cardiorespiratory fitness and brain health, particularly in gray matter and total brain volume -- regions of the brain involved with cognitive decline and aging.

Brain tissue is made up of gray matter, or cell bodies, and filaments, called white matter, that extend from the cells. The volume of gray matter appears to correlate with various skills and cognitive abilities. The researchers found that increases in peak oxygen uptake were strongly associated with increased gray matter volume.

The study involved 2,013 adults from two independent cohorts in northeastern Germany. Participants were examined in phases from 1997 through 2012. Cardiorespiratory fitness was measured using peak oxygen uptake and other standards while participants used an exercise bike. MRI brain data also were analyzed.

The results suggest cardiorespiratory exercise may contribute to improved brain health and decelerate a decline in gray matter. An editorial by three Mayo Clinic experts that accompanies the Mayo Clinic Proceedings study says the results are "encouraging, intriguing and contribute to the growing literature relating to exercise and brain health."

Ronald Petersen, M.D., Ph.D., a Mayo Clinic neurologist and first author of the editorial, says the most striking feature of the study is the measured effect of exercise on brain structures involved in cognition, rather than motor function. "This provides indirect evidence that aerobic exercise can have a positive impact on cognitive function in addition to physical conditioning," he says. "Another important feature of the study is that these results may apply to older adults, as well. There is good evidence for the value of exercise in midlife, but it is encouraging that there can be positive effects on the brain in later life as well."

The study's finding of higher gray matter volume associated with cardiorespiratory exercise are in brain regions clinically relevant for cognitive changes in aging, including some involved in Alzheimer's disease. The editorial calls those associations interesting but cautions against concluding that cardiorespiratory fitness correlations would affect Alzheimer's disease.

"This is another piece of the puzzle showing physical activity and physical fitness is protective against aging-related cognitive decline," says Michael Joyner, M.D., a Mayo Clinic anesthesiologist and physiologist, and editorial co-author. "There's already good epidemiological evidence for this, as well as emerging data showing that physical activity and fitness are associated with improved brain blood vessel function. This paper is important because of the volumetric data showing an effect on brain structure."

According to Mayo Clinic experts, moderate and regular exercise -- about 150 minutes per week -- is recommended. Good cardiorespiratory fitness also involves:

Not smoking Following healthy eating habits
Losing weight or maintaining a healthy weight level
Managing blood pressure and avoiding hypertension
Controlling cholesterol levels
Reducing blood sugar, which over time can damage your heart and other organs