Image by Dariusz Sankowski from Pixabay

August 28, 2023

Literature Review

1) What has happened in the realm of cancer incidence over the last decade? As one would expect, it is climbing especially for breast cancer and GI cancers. From the study: "In 2019, breast cancer had the highest number of incident early-onset cases.

By organ system, gastrointestinal cancers had the fastest-growing incidence rates of early-onset cancer, followed by cancers of the urinary system and the female reproductive system. Among gastrointestinal cancers in 2019, the most common types of incident early-onset cancers were in the colon and/or rectum, stomach, and pancreas. During the study period, the gastrointestinal early-onset cancers with the fastest-growing incidence rates were in the appendix, intrahepatic bile duct, and pancreas." (Koh et. al. 2023) This data set has paralleled my real life view. I know of way too many people with breast and GI cancers in the 30-50 year old age range.

2) Parasites remain a hot area of study. In the Journal Nature Communications we see a fascinating study looking at non autoimmune type 2 diabetes therapy with Nectar Americanis or hookworm. From the study: "The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomised, double-blinded clinical trial in Australia of hookworm infection in 40 male and female adults at risk of type 2 diabetes assessed the safety and potential metabolic benefits of treatment with either 20 (n = 14) or 40 (n = 13) Necator americanus larvae (L3) or Placebo (n = 13). Primary outcome was safety defined by adverse events and completion rate. Homoeostatic model assessment of insulin resistance, fasting blood glucose and body mass were key secondary outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced expected gastrointestinal symptoms, but completion rates were comparable to Placebo. Fasting glucose and insulin resistance were lowered in both hookworm-treated groups at 1 year, and body mass was reduced after L3-20 treatment at 2 years. This study suggests hookworm infection is safe in people at risk of type 2 diabetes and associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health." (Pierce et. al. 2023)

I am really in favor of this research realm and think that we should be treating patients with safe parasites that don't cause systemic disease and long term damage. Look at the work of William Parker and the podcast that we did a year and a half ago #7 Link.

3) Can apples and other plants help a babies nerves stay healthy? A new study from Monash University in Australia says that this may be happening. From the authors: "In animals, maternal diet and environment can influence the health of offspring. Whether and how maternal dietary choice impacts the nervous system across multiple generations is not well understood. Here we show that feeding Caenorhabditis elegans with ursolic acid, a natural plant product, improves axon transport and reduces adult-onset axon fragility intergenerationally. Ursolic acid provides neuroprotection by enhancing maternal provisioning of sphingosine-1-phosphate, a bioactive sphingolipid. Intestine-to-oocyte sphingosine-1-phosphate transfer is required for intergenerational neuroprotection and is dependent on the RME-2 lipoprotein yolk receptor. Sphingosine-1-phosphate acts intergenerationally by upregulating the transcription of the acid ceramidase-1 (asah-1) gene in the intestine. Spatial regulation of sphingolipid metabolism is critical, as inappropriate asah-1 expression in neurons causes developmental axon outgrowth defects. Our results show that sphingolipid homeostasis impacts the development and intergenerational health of the nervous system. The ability of specific lipid metabolites to act as messengers between generations may have broad implications for dietary choice during reproduction." (Wang et. al. 2023)

This study was done in worms which is a far cry from a human baby, however, these are the first links between a chemical like ursolic acid and health for a human. More research to follow. The chemical is naturally found in apples and herbs like basil, rosemary, thyme, oregano, and sage. My thoughts remain as always rooted in evolution. It makes sense that natural herbs and foods would have beneficial chemicals in them for species survival. My recommendation is to consume lots of herbs when pregnant.

4) When looking at post acute Covid 19 sequelae we see that the increased risk of death was not significant beyond 6 months after infection among non-hospitalized or home managed individuals. However, it was significantly elevated up to 2 years in hospitalized individuals. (Bowe B. et. al. 2023) This remains a testament to the severity of the inflammation in the hospitalized patients who had inflammatory risk factors, obesity, diabetes, cardiovascular disease and hypertension. The post acute issues were as follows: Sequelae are grouped by organ system. acute coronary disease, abnormal involuntary movements, acute kidney injury, chronic kidney disease, deep vein thrombosis, end-stage kidney disease, general anxiety disorder, gastroesophageal reflux disease, irritable bowel syndrome, ischemic cardiomyopathy, interstitial lung disease, myocardial infarction, neurocognitive decline, nonischemic cardiomyopathy, post-traumatic stress disorder, peptic ulcer disease, transient ischemic attack, venous thromboembolism.

The simple answer remains unchanged - control what you can control which is your immune health prior to infection so that one doesn't end up hospitalized with significant inflammation.

5) In a really interesting paper written by mathematicians in the Australia, we see a discussion of reasonable understanding of the current covid situation. With an original reproductive rate for the omicron variant of the virus of around 10, the spread in a naive immune population is massive, exponential. Now with broad based waxing and waning immunity nationally in all countries, we are in the endemic normalcy of a rapidly mutable virus. This reality has lowered the "effective" reproductive rate to about 1 on par with seasonal influenza. From the article: "And populations are highly varied, not homogeneous. Infections will be more frequent in groups with high contact rates, which typically means younger people. Mathematically, that means infection rates will be harder to budge in younger groups and relatively easier to bring down in older groups.

Interventions targeted towards vulnerable groups are likely to be more effective than blanket measures. Importantly, although reducing infection rates in the long term is difficult, vaccines provide direct protection for those who take them and continue to be highly effective at preventing severe disease. 

None of this is an argument that we shouldn’t try to reduce the prevalence of endemic diseases like COVID. But it does mean we can’t assume that a reduction in the number of infectious contacts will translate to an equivalent reduction in infection rates." "Decreasing the number of SARS-CoV-2 infections would be highly beneficial. It would reduce the acute health burden, the incidence of long COVID, and the level of risk for vulnerable groups. But it’s not a goal we can afford to pursue at any cost. There is a range of healthcare needs competing for limited resources, so any measures need to be cost effective. And that means being realistic about the size of the benefits they’re likely to deliver."(Plank et. al. 2023)

It remains clear to me in our clinic. Covid 19, since it's omicron iterations, is nothing more than a common cold. We have not had a single severe case, hospitalization or long Covid case that I am currently aware of despite looking vigilantly for it. This is not to say that other groups are not at risk. We remain watchful, but aware of the realities as they exist on the ground. As always, all known high risk groups should follow vaccine booster recommendations.

Dr. M

Koh JAMA

Pierce Nature Communications

Wang Nature Cell Biology

Bowe Nature Medicine

Plank The Conversation