UPShots Clinical Research Roundup

Research on diet, nutraceuticals, and herbal medicine continues to grow worldwide. Here are summaries of a few recent studies that have grabbed our attention at Holistic Primary Care.

Cinnamon Fosters Weight Loss in Type 2 Diabetes

A gram of cinnamon (Cinnamomum cassia), thrice daily, promoted weight loss and lowered hemoglobin A1c levels in a small cohort of people with type 2 diabetes.

Cinnamomum cassia (Image: Amphaiwan/Shutterstock)

Researchers at the University of Guadalajara, Mexico randomized 18 patients to placebo or cinnamon in capsules. They gathered biometric data including lipid profiles and measures of endothelial function, at baseline and again at 12 weeks.

The study participants ranged in age from 40-65 years. All had been diagnosed with type 2 diabetes within the last 12 months, and all were on metformin, 850 mg daily. They were randomized to treatment with the cinnamon capsules or placebo, for 12 weeks.

Compared with the placebo group, patients taking cinnamon (1 gram, roughly half a teaspoon per day), showed statistically significant reductions in mean body weight (79.9 ± 9.0 kg vs 81.4 ± 10.4 kg), and body mass index (30.1 ± 4.2 kg/m2 vs 30.6 ± 4.2 kg/m2). There also appeared to be a significant effect on HbA1c (45 ± 2.1 mmol/mol vs 53 ± 5.4 mmol/mol)—and remember that’s beyond the effect of the metformin (Delgadillo-Centeno JS, et al. J Med Foods. 2023).

The investigators used brachial-ankle pulse wave velocity and flow mediated dilation techniques to assess arterial stiffness and endothelial dilation, but found no difference between the cinnamon and placebo groups. Likewise, there were no significant differences in blood pressure, fasting glucose, or lipid profiles associated with cinnamon intake. Still, the observed effects on weight and HbA1c are impressive, and warrant further study.

(Thanks to the American Herbal Pharmacopoeia for calling attention to this study).

To Improve Fibromyalgia, Go Gluten-Free

Six months on a gluten-free diet can result in significant reduction of pain and other symptoms of fibromyalgia, even in people who do not show overt signs of celiac or gluten intolerance.

That’s the message from a clinical research team at La Sapienza University, Rome, who studied the impact of the GF diet in 20 postmenopausal women with treatment-refractory fibromyalgia and no history of celiac disease.

All had previously been treated with NSAIDs, duloxetine, or pregabalin. 5 of the women had comorbidities in addition to fibromyalgia, including thyroiditis, Sjogren syndrome, and chronic urticaria. Four had prior diagnoses with breast or thyroid cancer.

The researchers calculated Fibromyalgia Symptom Severity (SS) and Widespread Pain Index (WPI) scores at baseline, and again after the women had been on a strict GF diet for 6 months. Following this, the women returned to their prior non-restricted eating patterns for 3 months, after which their pain scores were assessed again. They then resumed the GF diet for another 6 months. 

The impact of the dietary changes was clear: after 6 months gluten-free, the cohort showed an average 24% drop in WPI scores, and a 36% drop in SS scores. Three months after reintroducing gluten-containing foods, the WPI and SS numbers bounced back to near-baseline levels. After the second 6-month round of GF dieting, the scores dropped again, and by roughly the same margins (Bruzzese V, et al. Reumatismo. 2023).

Notably, participants’ weight and BMI remained stable across the dietary changes.

“Gluten could be an inflammatory trigger, even in subjects without non-celiac gluten sensitivity, and in those subjects that are genetically predisposed and in whom there is damage to the intestinal barrier,” writes lead author Vincenzo Bruzzese. He added that observational studies and anecdotal case reports in the past have pointed to correlations between gluten and autoimmune diseases, such as rheumatoid arthritis.

Likewise, some authors have reported associations between fibromyalgia and abdominal symptoms like pain and diarrhea, attributable to irritable bowel syndrome (IBS).

Going gluten-free is probably not a panacea for fibromyalgia, but it is certainly worth trying, especially with patients whom drug therapies have failed. A GF diet is a relatively low-cost approach, with few risks, and a lot of potential benefit.

Veg-Rich Diet Cuts Crohn’s Risk by Half

A prospective study of nearly 400,000 people in 8 European countries, followed for more than 10 years, showed that those who ate the highest quantities of unprocessed or minimally processed foods fruits and vegetables had half the risk of Crohn’s disease compared with those who ate the least produce.

Antoine Meyer, MD, and colleagues of the INSERM Centre for Research in Epidemiology and Population Health in Paris, looked at the relationship between consumption of processed versus whole foods and the risks of Crohn’s disease (CD) and ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort.

This database provided detailed information on 413,590 adults from 8 European countries, gathered over a 13-year period. During that time there were 179 new cases of CD, and 431 new cases of UC.

Statistically, the people who ate the highest proportions of unprocessed or minimally processed foods had a 43% lower risk of developing CD. This correlation was especially pronounced for consumption of fruits and vegetables (Meyer A, et al. Clinical Gastroenterol Hepatol. 2022). That said, the researchers did not find a similar risk reduction for ulcerative colitis.

Still, clinicians “should be advising our patients to consume minimally processed or unprocessed foods to cut the risk of Crohn’s disease, especially our high-risk patients, like those with a close relative suffering from the condition,” said Dr. Meyer.

High Flavonol Intake Mitigates Risk of Frailty

New data from more than 1,700 participants in the Framingham Heart Study show that increased intake of flavonol and quercetin—two key plant-derived flavonoids—reduces frailty in people over age 55.

Researchers from the Division of Human Nutrition and Health, Wageningen University, the Netherlands, and the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, quantified flavonoid intake based on food frequency questionnaire (FFQ) data gathered from a subset of the Framingham cohort from 1998 to 2001. They plotted this against indicators of frailty during that period, and again the years from 2011 to 2014.

After 12.4 years from baseline, 224 of the subjects (13.2%) individuals developed measurable signs of frailty.

The mean total flavonoid intake was 309 mg/d (SD ± 266). For each 10 mg/day increase in flavonol, there was a 20% percent lower odds of frailty onset. Quercetin appeared to be a particularly important flavonoid in this context. For every 10 mg/day increase in quercetin intake, the researchers observed a 35% lower odds of frailty onset (Oei S, et al. Amer J Clin Nutrit. 2023.). This suggests that certain subclasses of flavonoids may have distinct effects on aging bones and muscle.

Although no association was observed between total flavonoid intake and frailty onset in adults, a higher intake of flavonols was associated with lower odds of frailty onset, with a particularly strong association for quercetin,” the authors note. “This hypothesis-generating study highlights the importance of assessing specific subclasses of flavonoids and the potential of dietary flavonols and quercetin as a strategy to prevent the development of frailty.”

Broccoli Sulforaphane Improves Mood, Boosts Brain Function

Daily supplementation with 30 mg of glucoraphanin—a broccoli-derived compound that is converted to sulforaphane during digestion—led to measurable improvements in cognitive processing speed and reductions in negative mood states in a cohort of 144 Japanese adults between the ages of 60 and 80 years.

Broccoli (Image: Voyager_human/Shutterstock)

Prior studies have shown that increased intake of cruciferous vegetables (and produce in general) correlated with less frequent negative moods, and that high sulforaphane (SFN) intake could improve memory and mental processing speed. Researchers at Tohoku University, Sendai, Japan, hypothesized that supplementation with a precursor like glucoraphanin could potentially raise SFN levels enough to impact mood and cognitive performance.

To test that, they recruited a cohort of generally healthy older people with no signs of cognitive impairment, depression, or any other neurological condition. They randomized them to daily supplementation with a placebo or capsules containing 30 mg of glucoraphanin, for 12 weeks.

Glucoraphanin is a glucosinolate compound produced by broccoli, mustard, several types of cabbage, and other crucifers. In the human gut, it is converted into SFN by an enzyme called thioglucosidase (myrosinase) produced by certain commensal microbes.

The Tohoku University team used an array of standardized scales to assess executive function, processing speed, visual, and verbal episodic memory performance, verbal short-term memory performance, and working memory at baseline, and again after 12-weeks. They quantified mood using a short version of the Profile of Mood State Second Edition (POMS2).

At Week 12, the SFN supplementation group showed marked improvements in processing speed on several measures, particularly on the Symbol Search (SS) test, compared with the placebo group.

Similarly, the SFN-treated group showed reduced negative emotion scores on the POMS2 and improved Total Mood Disturbance (TMD) scores.

Predictably, the SFN group showed higher levels of sulforaphane -N-acetyl-L-Cysteine (NAC) levels, a urine test indicating the level of SFN absorption and, by inference, compliance with the supplement regimen.

“These results indicate that nutrition interventions using SFN can have positive effects on cognitive functioning and mood in healthy older adults,” the authors report (Nouchi R, et al.Front Aging Neurosci, 2022).

Animal studies had hinted that increased SFN intake could potentially lead to changes in biomarkers of neuroplasticity like brain derived neurotrophic factor (BDNF), inflammatory markers like TNF-α, or markers of oxidative stress like heme oxygenase-1 (HO-1). Though they measured these markers, the Tohoku University team did not see any major differences between the SFN and placebo groups.


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