Welcome to the November 2022 issue of Research Extracts. “The Extracts” is designed to keep busy practitioners and savvy consumers up to date on the latest research on diet, nutrients, botanicals, the microbiome, the environment, and lifestyle approaches to good health. Our medical team, which includes NDs, MDs, PhDs, RDs, an MS, and an LAc, has summarized the essence of several interesting recent studies.

In this issue: (1) this month’s Mental Health Moment #1 – antioxidants for motivation, (2) Mental Health Moment #2 – social support and cognitive function, (3) late night eating and weight gain, and (4) sleep and cardiovascular health.

Mental Health Moment #1: Will Antioxidants Motivate You?

The brain is susceptible to oxidative stress, just like other organs in the body, and different areas of the brain react differently to these stressors. Previous research has identified mitochondrial function in the nucleus procumbens (NP) to be an area of the brain associated with motivation. In this current series of studies, the researchers used proton magnetic resonance spectroscopy (H-MRS) in human males and rats to evaluate various metabolites in the NP and how these metabolites relate to motivational behaviors. The research builds on previous human research that shows higher glutamine levels in the NP (a precursor to glutamate – one of three amino acids comprising glutathione) are related to improved motivational behavior. Was increased glutathione to credit for this? If so, then glutathione, the most important antioxidant made in the body, might be cleaning up free radicals in this area of the brain.

The human study was conducted on 22 men, ages 20-30. They participated in a series of motivational exercises with monetary incentive – one series in solitary and one as competition with other participants. Several NP metabolites were measured using H-MRS. Glutathione was found to be the primary one associated with performance in motivational tasks, although phosphatidylethanolamine also showed some relationship. There was no relationship with the other metabolites measured. The remainder of the experiment focused only on glutathione. The motivational tasks were split in half temporally (first half, second half) and the participants were further divided into high- and low-glutathione groups. At the end, participants in the high-glutathione group sustained their performance through both halves of the trial, whereas those in the low-glutathione group had a significant reduction in the number of successful trials in the second half. This suggests glutathione might benefit sustained motivation.

Then the researchers performed a series of studies in rats. The first study used a similar design as the human study and found the rats with higher NP-glutathione levels outperformed the rats with lower levels. Then glutathione was suppressed with a glutathione inhibitor, resulting in decreased motivation. And finally, to establish a potential mechanism for increasing glutathione levels, the rats were divided into two groups: (1) N-acetylcysteine (NAC) in their drinking water for two weeks, or (2) regular water without NAC. NAC was chosen because it is a source of cysteine – one of the three amino acids that make up glutathione – and it has also been shown in previous studies to increase glutathione levels in the brain. The rats in the NAC group experienced increased NP-glutathione levels and demonstrated improved reward-based motivational performance and endurance.

Contributed by Kathi Head, ND

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Contributor’s note: Together, this series of experiments appears to indicate the importance of addressing oxidative stress as part of a brain support program and points to the possible benefit of NAC and/or glutathione to support motivation.* Thorne offers both NAC and glutathione as stand-alone supplements. In addition, Thorne’s SynaQuell and SynaQuell+ – two powdered supplements formulated to support brain health – both contain glutathione.*

Mental Health Moment #2: Having Someone to Listen Might Protect Cognitive Function 

Brain health is a complicated area, with many factors contributing to it. Some are difficult to maintain, like exercise and diet. Some are complicated, like genetics and environmental exposures. A recent study has demonstrated that a specific type of social support might be more important than we thought. 

In response to previous findings that social isolation, loneliness, and cognitive decline are often associated, investigators utilized data from 2,171 participants in the multi-generational Framingham Study (minimum age 45, average age 63, 54% female) to assess whether five types of social support are associated with cognitive resilience; i.e., the ability to maintain cognitive function despite factors that increase risk for cognitive decline.

Cerebral volume, measured by MRI and adjusted for head size, was used as an indicator of the collective structural factors that can contribute to brain health or vulnerability, because loss of brain size is often observed with cognitive decline. A small battery of cognitive tests assessing factors such as logical memory and visual recall were used to assess functional cognitive health. The availability of five types of social support – listening, advice, love-affection, emotional support, and sufficient contact – were assessed using the Berkman-Syme Social Network Index questionnaire. Various statistical models accounting for confounding factors (other things known to affect cognitive health) such as sex, age, and education were applied to the data. 

The study found that participants younger than 65 with high listening support availability (having someone to listen supportively most of or all the time) had significantly higher global cognitive performance than would be expected for their brain volume and as compared to participants with similar brain volume and low listening support availability (having someone to listen available none, a little, or some of the time). Although this study does not conclusively show that having access to supportive listeners is protective of cognitive health, it does suggest it might be something to seek out. 

Contributed by Sheena Smith, MS MA 

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Eating Late Increases Hunger and Modifies Metabolism

The timing of meals – eating late versus eating early – is associated with weight gain and obesity, although the connections between late eating and obesity are not well understood. In a recent randomized, controlled, crossover trial, healthy participants (ages 20-60 with BMI in the overweight or obese range and without diabetes) completed a controlled, inpatient protocol that included an early eating phase and a late eating phase. The order of early or late eating was randomized, and participants completed a wash-out period between the two eating phases. Laboratory analyses, including blood labs and subcutaneous adipose tissue biopsy, and hunger/appetite were measured during both study phases.

Late eating resulted in increased hunger, as well as an imbalance of the appetite-regulating hormones ghrelin and leptin, a hormonal pattern associated with increased hunger. Participants also had lower energy expenditure and decreased core body temperature associated with late eating. The adipose tissue biopsies revealed decreased fat breakdown and increased fat accumulation with late eating. Overall, the results suggest late eating leads to unfavorable changes in hunger and metabolism that might result in increased obesity.

Contributed by Jennifer L. Greer, ND, MEd

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Sleep and Cardiovascular Health

Sleep is often considered to be one of the three pillars of health because of its far-reaching effects on overall health and wellbeing. Negative sleep behaviors and sleep disorders, such as insomnia and sleep apnea, are linked to poorer cardiometabolic health and increased risk for cardiovascular disease. Poor sleep quality also has an adverse effect on other lifestyle behaviors, including poor diet quality and lower physical activity levels, which are also contributing factors to cardiovascular disease risk. 

This study examined the sleep characteristics of sleep duration, efficiency, and regularity, as well as sleep apnea, insomnia, and daytime sleepiness. These were analyzed alongside cardiovascular health metrics, including blood pressure, BMI, blood lipids, physical activity level, and dietary patterns to evaluate the interconnectedness between sleep patterns and cardiovascular health. In addition, incidence of cardiovascular events, including myocardial infarction, angina, and stroke were measured for the duration of the study. The results show that higher daytime sleepiness, high variability in sleep duration and timing, and sleep apnea are associated with a higher risk for cardiovascular disease and poorer cardiovascular health. Longer sleep duration and higher sleep efficiency are associated with lower cardiovascular disease risk. 

Contributed by Carly Duffy, MPH, RD

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Contributor’s note: Thorne offers supplements that support healthy sleep patterns and potentially have trickle-down effects on cardiovascular health as seen in this study. Explore Thorne’s entire sleep support suite here. Not sure where to start? Consider taking Thorne’s Sleep Test – an easy, at-home test that measures melatonin and cortisol levels at four periods during the day.