Welcome to the April 2023 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 nutrition, an MS biology, and an LAc, summarizes the essence of several interesting recent studies.

In this issue: (1) Mental Health Moment: microbiome and depression, (2) grape polyphenols and Akkermansia, (3) blueberries and athletic performance, and (4) the Mediterranean diet and inflammation.

Mental Health Moment: Gut Bacterium Linked to Depression in Women

Depression affects women almost twice as frequently as men. This is believed to be due in part to the decreasing estradiol levels women experience during menopause and estradiol’s effects on mood – estradiol being the primary form of estrogen in nonpregnant women prior to menopause. This study explored the effects of the gut microbiome of younger women (average age 27) on depression status.

The group of women with depression (n=91) had significantly lower baseline serum estradiol levels than the women without depression (n=98). To determine whether the gut microbiome affects estradiol levels, researchers supplied synthetic estradiol to the gut microbiota of both groups of participants. The results showed that 77 percent of the estradiol was degraded in the depressed group compared to 19 percent in the non-depressed group over a 120-minute period. These results suggest the gut microbiota of the women with depression degraded estradiol more rapidly.

The researchers then measured the impact of changing gut bacteria on estradiol levels and their impacts on mood and depression status. To do this, fecal samples providing gut microbiota from both the depressed and non-depressed groups were transplanted into two groups of mice. Significantly lower estradiol levels were found in the mice that received a fecal transplant from the depressed women. To assess the impacts on depression-like behaviors, the mice went through several behavioral experiments. The mice that received a fecal transplant from the depressed women and had lower estradiol levels displayed depression-like behaviors.

The researchers then isolated gut microbes from the depressed women and identified Klebsiella aerogenes as a primary estradiol-degrading microbe. This was confirmed by testing the estradiol degradation rates in mice that had K. aerogenes transplanted in their gut. Looking again at the fecal samples from the female participants, the women in the depression group had a higher abundances of K. aerogenes in their gut compared to women in the non-depressed group, indicating an association between the gut microbiome, serum estradiol, and depression status.

Contributed by Carly Duffy, MPH, RD

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Grape Polyphenols Increase Akkermansia muciniphila for Improved Gut Health

Emerging evidence points to the gut health benefits of the bacterial species Akkermansia muciniphila – for balancing low-grade inflammation and stimulating the thickness of intestinal mucin (the primary component of the mucus layer) to improve gut barrier function. Therefore, finding nutrients that nurture the growth of Akkermansia could benefit GI health. 

This study examined the effect of grape polyphenols on Akkermansia growth and subsequent gut health in mice, building on previous research in animals and humans that shows increased Akkermansia growth after grape polyphenol supplementation.

In this study, mice were fed either a low-fat or high-fat diet with or without grape polyphenols (GP) for 12 weeks. Increased Akkermansia was seen in both GP groups, but not in the groups not given polyphenols. After 12 weeks, the relative abundance of cecum Akkermansia was 29 and 39 percent in the low-fat GP group and high-fat GP group, respectively. By comparison, the low-fat and high-fat non-GP groups had 6- and 7-percent Akkermansia abundance, respectively. Along with increased Akkermansia, the mice on a high-fat diet with grape polyphenols in their feed had decreased lipopolysaccharide (LPS) binding protein compared to the mice fed a high-fat diet without GP; elevated LPS is a sign of inflammation. There was an overall decrease in fecal bacterial count in the GP groups, despite the increase in Akkermansia. The researchers speculated that grape polyphenols selectively inhibited certain competing bacteria, allowing Akkermansia to flourish.

An unexpected finding was thinning of the mucus layer in the colon in the GP groups, but without accompanying signs of inflammation. The implication of this finding is unclear.

Looking to support Akkermansia levels? Consider Thorne’s Grape Seed Extract – which contains a grape seed polyphenol/phospholipid complex. Other polyphenols, including those in Prebiotic +, also have been shown to benefit Akkermansia levels. Would you like to know which bugs are living in your gut – the good, the bad, and the indifferent? Then check out Thorne’s at-home Gut Health Test.

Contributed by Kathi Head, ND

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Eating Wild Blueberries Might Improve Athletic Performance in Active Men

Wild blueberries are rich in antioxidants called anthocyanins, which previous research has shown to improve fat oxidation and reduce oxidative stress in sedentary individuals. Less is known about wild blueberry consumption in athletes, a population with increased oxidative stress and higher energy needs due to heavy training regimens. Because fat oxidation is a source of energy, enhancing fat metabolism in athletes could potentially lead to improved athletic performance.

In a study of 11 healthy, young athletic males, the participants initially followed an anthocyanin-free diet for two weeks. Following this wash-out period, blood and urine samples were obtained, and the participants completed a controlled exercise protocol to maximize fat oxidation. For the next two weeks, the participants consumed wild blueberries twice daily while following the initial wash-out diet. Blood and urine samples after the same exercise protocol were obtained a final time.

Consumption of wild blueberries led to significant increases in fat oxidation throughout the exercise protocol with decreased carbohydrate oxidation and reduced blood lactate. The authors note one additional benefit of the study compared to previous studies is that the athletes completed the exercise protocol in a fasted state – fasted exercise is known to improve fat oxidation. The results of this study suggest that consuming wild blueberries as part of the daily diet can improve athletic performance by enhancing fat oxidation.

Contributed by Jennifer L. Greer, ND, MEd

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Mediterranean Diet Decreases Inflammation

Chronic inflammation is associated with many chronic health conditions, including cardiovascular disease, metabolic syndrome, type 2 diabetes, arthritis, and certain cancers. The fact that the Mediterranean diet (MedDiet) is considered an anti-inflammatory diet is not newsworthy; Thorne has written much about it on Take 5 Daily, we include it in many of our Thorne Wellness Guides, and generally we are big boosters of the diet. Many of the studies of the health effects of the MedDiet looked at diet questionnaires that tend to rely on retrospective memory to evaluate dietary habits. What’s interesting about this study is that it was a prospective study in which half the participants were assigned a MedDiet while the other half remained on their not-as-healthy “habitual diet.”

Australian adults (average age 71) were assigned to the MedDiet (n=80) or their habitual diet (n=72) for six months. The study’s primary objective was to determine whether a switch to the MedDiet decreased the dietary inflammatory index (DII) – an assessment of specific dietary factors and how they impact inflammation either positively or negatively – and how this correlates with cardiometabolic changes. Significant decreases in DII scores were seen at both the 2- and 4-month evaluations in the MedDiet group, but not in the habitual diet group. In terms of cardiometabolic risk factors, adherence to the MedDiet, compared to the habitual diet, resulted in significant decreases in triglycerides, systolic blood pressure, and F2-isoprostanes (a reflection of oxidative stress and potential free radical damage) at both the 3- and 6-month evaluations. Endothelial function measured by flow-mediated dilation was significantly better in the MedDiet group at six months.

Contributed by Kathi Head, ND

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