Welcome to the April 2021 edition 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 of the most interesting recent studies.

In this issue you will find new studies on: (1) the connection between allergic reactions and IBS, (2) the brain-placebo effect, (3) blood levels of sodium and COVID mortality, and (4) frequency of post-COVID brain fog.

Could localized allergic reactions be a cause of IBS symptoms?

Irritable bowel syndrome (IBS) is a constellation of symptoms, including abdominal pain and altered bowel patterns, that affects more than 10 percent of U.S. adults. Although the exact cause of IBS is unknown, it often develops after a gastrointestinal infection. A recent study investigated the theory that IBS symptoms are caused by a localized allergic reaction in the digestive tract that is stimulated by a bacterial infection.

In the study, mice were infected with a bacterial species while also being exposed to egg protein. After the bacterial infection cleared, the mice exposed to egg protein continued to develop symptoms, such as diarrhea, increased water content in the stool, and decreased intestinal transit time. Uninfected mice, however, did not have similar symptoms after egg protein exposure.

Egg protein-specific IgE antibodies – immune cells associated with allergic response – were present in the colons of the infected mice, although not in their small intestines or blood, indicating the allergic response was limited to the colon.

To investigate whether a similar localized allergic response is present in humans who have IBS, participants’ colons were injected with a solution of common food allergens – gluten, soy, wheat, and milk – none of which the participants had a known allergy to. In each participant with IBS, a localized allergic reaction to at least one of the foods occurred. Only two of the non-IBS participants experienced a localized reaction.

Although this study does not definitively determine the cause of IBS, the research team reported the information is a breakthrough in understanding how tolerance to food allergens can be lost in individuals who have IBS, leading to a localized immune response in the colon following food ingestion. Similar mechanisms previously identified in individuals with asthma and allergic rhinitis could help to identify potential therapies for future study that could be beneficial in the treatment of IBS.

Are you interested in learning more about your gut health? You can with this easy, at-home Gut Health Test. Results provide extensive insights into what is making your gut tick, plus individualized diet, lifestyle, and supplement suggestions based on your results.

Contributed by Jennifer L. Greer, ND, MEd


  • Aguilera-Lizarraga J, Florens M, Viola M, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature 2021;590(7844):151-156. doi:10.1038/s41586-020-03118-2

Your brain on placebo

Medicine has long been fascinated with the so-called “placebo effect.” According to the National Center for Complementary and Integrative Health, the placebo effect is, “a beneficial health outcome resulting from a person’s anticipation that an intervention will help.”(1) In scientific studies, a placebo (a mock substance designed as an inactive control to compare to the active substance being studied) is an important factor in understanding how well a drug or other treatment is working relative to a substance not expected to do anything. But sometimes – in fact, more often than you might expect – the participants in the placebo arm of a clinical trial obtain the same or similar effects as the participants taking the trial’s active material. This tells us that somehow “anticipation” is doing something real – the question is what?

One of the more frequently investigated forms of the placebo effect is placebo analgesia (pain relief). Many of these studies use neuroimaging, such as fMRI (functional magnetic resonance imaging). A recent meta-analysis of 20 independent studies sought to map, and thus better understand, the effects of placebo analgesia as determined by fMRI results.(2) The authors utilized a voxel-wise comparison, a computational approach to evaluating brain images that allows for the comparison of differences across the entire brain (versus other methods that are often focal).

The analysis found strong evidence that placebo analgesia significantly reduces activity in areas of the brain associated with pain and nociception (the sense of impending pain). However, they also found that placebo analgesia affected other areas of the brain, such as those involved in self-regulation and decision making.

Their overall conclusion is that placebo analgesia involves more of the brain than the pathways dedicated to pain and is likely the sum total of a combination of neural processes working together. They suggest the importance of future studies looking into the neurochemical alterations that correlate with the observed changes in functional brain activity.

This study takes us closer to understanding how the placebo effect is produced. If this could be reliably reproduced, then it might prove to be a valuable tool in safely reducing the use of a variety of medications and therapies.

Contributed by Jacqueline Jacques, ND


  1. Placebo Effect. NCCIH. https://www.nccih.nih.gov/health/placebo-effect [Accessed March 28, 2021]
  2. Zunhammer M, Spisák T, Wager T, Bingel U. Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data. Nat Commun 2021;12(1):1391. doi:10.1038/s41467-021-21179-3
  3. Full text here

High blood sodium levels could warn of elevated COVID-19 risk in hospitalized patients 

Contributed by Sheena Smith, MS MA 

A recent study followed up on observations that blood sodium levels might be associated with COVID-19 outcomes. The study included 488 patients (43.2% female), median age 68 and positive COVID-19 test, who were admitted to one of two hospitals in London, England. Their serum sodium levels were measured on days 1 (admission), 3, 6, 11, and 18 (or until death or discharge).

On admission, 29.9 percent of participants had non-normal blood sodium levels, with 5.3 percent high and 24.6 percent low. This increased to 62.1 percent over the course of hospitalization. Total in-hospital mortality was 31.1 percent at a median of seven days, median hospital stay for survivors was eight days, and length of stay was not associated with sodium levels.

There was no significant difference in mortality between patients with low sodium that remained low during hospitalization and those who began with low sodium and were corrected to normal levels. Overall, low sodium was not associated with mortality, with the exception of individuals who also had low blood volume, the latter of which corresponded with a significantly higher 40.9-percent mortality rate compared to normal blood sodium and volume levels.

Interestingly, low sodium levels were associated with an increased likelihood of requiring respiratory support, although the authors noted the possibility of confounding factors that could not be accounted for in this study.

There was a significant association between mortality and high blood sodium during hospitalization, with 45.7-percent higher mortality when patients had both high and low sodium and 56.6-percent higher mortality if they only had high sodium levels. Specifically, high blood sodium levels earlier in the illness (at the day 3 and/or 6 measurement) were associated with more than double increased mortality risk.

Patients with the most increase in sodium between admission and day 6 had the highest mortality rate. The authors noted the novel finding that sodium levels tended to increase during hospitalization and strongly recommended monitoring and maintenance of sodium levels and blood volume during treatment.


  • Tzoulis P, Waung J, Bagkeris E, et al. Dysnatremia is a predictor for morbidity and mortality in hospitalized patients with COVID-19. J Clin Endocrinol Metab Published online February 24, 2021. doi:10.1210/clinem/dgab107 
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Post-COVID brain fog is more common than you think

Contributed by Kathi Head, ND

Although the majority of individuals recover from COVID-19 without residual symptoms, some, even those who had a mild case, continue to have symptoms for weeks or months following the initial infection. This situation is being referred to as post-COVID syndrome, long COVID, or “long-hauler” syndrome. One of the more common complaints is lingering brain fog, and in fact, COVID-19 has emerged as a very specific cause of brain fog.

A new study has examined the pervasiveness of post-COVID brain fog. One hundred consecutive patients (average age 43; 70% female) presenting at Northwestern Memorial Hospital’s Neuro-COVID clinic between May and November 2020 were evaluated. Participants were included if they had not been hospitalized for respiratory symptoms during the acute infection and if they had symptoms that persisted for at least six weeks, post-COVID.

Patients were evaluated in person or by televisit (televisits only in May, June, and July). A complete neurological exam was performed on the 52 patients seen in person, and a limited evaluation was done on the 48 seen remotely.

At least four neurological symptoms were reported by 85 percent of participants. The 10 most frequent neurological symptoms were: brain fog (81%), headache (68%), numbness/tingling (60%), distorted or complete lack of sense of taste (59%), loss of sense of smell (55%), muscle aches (55%), dizziness (47%), pain (43%), blurred vision (30%), and tinnitus (29%). Many reported fluctuating symptoms.

On neurological exam, the most frequent findings were short-term memory loss and attention deficits. Self-assessed quality of life for cognition scores were significantly lower than the general population. Patients who presented to this clinic with residual neurological symptoms had higher prevalence of preexisting autoimmune disease and anxiety/depression, suggesting these conditions might predispose to post-COVID neurological symptoms in COVID long haulers.