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Category: GRDS

Medication Accumulation in Gut Bacteria May Curb Drug Effectiveness, Alter Gut Microbiome

October 05, 2021 2:06 pm

NEW YORK (Reuters Health) – Many common medications such as antidepressants, diabetes and asthma drugs can accumulate in gut bacteria, altering bacterial function and potentially reducing drug effectiveness, researchers say. “It was surprising that the majority of the new interactions we saw between bacteria and drugs were the drugs accumulating in the bacteria, because up until now biotransformation (chemical modification) was thought to be the only way that bacteria affect drug availability,” Dr. Kiran Patil of the MRC Toxicology Unit, University of Cambridge, told Reuters Health by email. “We also were surprised to see the stark effect of bioaccumulation on bacterial metabolism and on community composition.” “There will likely be very strong differences between individuals, depending on the composition of their gut microbiota,” he noted. “We saw differences even between different strains of the same species of bacteria.” As reported in Nature, Dr. Patil and colleagues grew 25 common strains of gut bacteria and investigated their interactions with 15 structurally diverse oral drugs. The team identified 70 bacteria-drug interactions, 29 of which had not been previously reported. Seventeen of the newly discovered interactions could be ascribed to bioaccumulation – i.e., bacteria storing the drug intracellularly without chemically modifying it, and in most cases without bacterial growth being affected. To gain additional insight, the team investigated the molecular basis of bioaccumulation of the antidepressant duloxetine. They found that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the affected bacteria. When tested in a microbial community of drug accumulators and non-accumulators, duloxetine markedly altered the small molecules produced by the drug-accumulating bacteria, which the non-accumulators fed on; this caused an overabundance of consuming bacteria, thereby unbalancing the composition of the community. Further, the team validated their findings in C. elegans; worms grown in bacteria that accumulated duloxetine behaved differently from those grown in bacteria that did not accumulate duloxetine. Summing up, the authors state, “Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner.” Dr. Patil added, “Next steps will be to take forward this basic molecular research and investigate how an individual’s gut bacteria tie in with differing individual responses to drugs such as antidepressants – differences in response, drug dose needed, and side effects like weight gain.” “If we can characterize how people respond depending on the composition of their microbiome, then drug treatments could be individualized,” he said. “The clinical relevance will hopefully be clear in the next 2-3 years.” Dr. Libusha Kelly of Albert Einstein College of Medicine in New York City commented on the study in an email to Reuters Health, “This work highlights the broad importance of microbe/drug interactions in drug bioavailability and the unrecognized potential for bioaccumulation of drugs to modify metabolite secretion in microbial communities.” “As the authors note,” she said, “this study in bacterial isolates is only the first step towards understanding how bioaccumulation might influence drug metabolism and microbial community composition in the context of the far more complicated communities of microbes in the human body.”
“There are likely additional, cryptic, ways in which bacteria alter bioavailability and drug metabolism in the human body,” she said. “Furthermore, we do not understand how microbiome/drug interactions influence drug efficacy and safety in individual patients, which limits the clinical utility of our field currently. However, the authors uncover an exciting direction for future research.” Source: https://go.nature.com/3CxioHd Nature, online September 8, 2021. Reuters Health Information © 2021

COVID Vaccines

March 05, 2021 3:50 pm

There are no known contraindications from a weight-loss surgical perspective to prevent a post-surgical patient from getting the COVID vaccines.

A patient who has had a Duodenal Switch, Lap Sleeve Gastrectomy, RNY Gastric Bypass, or revisions to Weight Loss Surgery should have the COVID vaccine. The vaccination should be avoided for a few weeks after surgery. For other possible contraindications, please consult your PCP.

Here is a summary of the vaccines and the details of each one approved as of the publication date.

 

 

 

Vitamin D and Covid -19

May 07, 2020 9:24 am

We are all aware of the many roles that Vitamin D plays in our bodies. This includes immune function in addition to all the regulatory roles that Vitamin D plays in several physiologic reactions. There may be a correlation of low Vitamin D and COVID-19 infection increasing death risk as looked at in research articles.

Covid -19 in a subset of patience causes significant lung injury. These patients require mechanical ventilation.

Previously reported publications have suggested a possible correlation between ace inhibitors and increased risk of pulmonary complications of Covid -19. Some researchers suspect that the Covid-19 may be able to enter lung cells by the ACE receptors.

Shown is the initial entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells, primarily type II pneumocytes, after binding to its functional receptor, angiotensin-converting enzyme 2 (ACE2). After endocytosis of the viral complex, surface ACE2 is further down-regulated, resulting in unopposed angiotensin II accumulation. Local activation of the renin–angiotensin–aldosterone system may mediate lung injury responses to viral insults. ACE denotes angiotensin-converting enzyme, and ARB angiotensin-receptor blocker. (N Engl J Med 2020; 382:1653-1659)

Vitamin D may positively implact the receptor ACE2. This study, report clear correlation between the high death rate with low vitamin D levels in Covid infected patients. There are limitation to this study that the attached abstract outlines.

Our take home message would be to please make sure you have updated labs and that you are all taking the recommended Vitamin D based on your surgical anatomy and laboratory values, not just an average non-bariatric person recommended dose.

https://www.dssurgery.com/wp-content/uploads/2020/05/manuscript.pdf

Protein Intake

October 14, 2019 7:08 am

Protein intake requirements change over time following weight loss surgery. This is based on the requirements imposed on our body by a number of variables. These include, activity level, muscle mass, over all health condition to name a few.

A very young muscular athletic male with a BMI or 30 will require much higher protein intake (and absorption) that an inactive older Female with the same BMI. The same young athletic male will require much higher protein intake is he is recovering from a surgery than his baseline.

As we have stated in the past, the protein intake, should be adequate and not excessive. High level of protein intake that are not accounted  for based on muscle mass and activity level, will eventually result in weight gain. The best measure of protein intake in a stable weight patient over 3-4 years post op  is their albumin and protein level. Following your yearly laboratory values at a minimum is an important part of weight loss surgery follow up care.

You also need to adjust protein intake when necessary. Protein needs increase depending on physical needs, infection, healing, pregnancy, surgery, age, injury, etc. Plastic surgery requires higher protein needs for appropriate healing.

Information on protein sources and quality here.

The basic formula for protein intake is 1gm/kg of ideal body weight. The calculator below will provide a guide for the protein into based on your stable weight in lbs.

Sleeve And Weight Regain

July 22, 2019 9:50 am

Sleeve gastrectomy has become the most frequently performed operation in the US. Sleeve as a part of the Duodenal Switch or as a stand alone operation has been offered in our practice for nearly 20 years. As a precondition to this, patients’ choosing to have the sleeve, especially with high BMI (>45) and those with metabolic conditions (diabetes, high cholesterol or triglycerides, PCOS, and others) we have always recommended Duodenal Switch as the procedure of choice instead of the Sleeve Gastrectomy due to improved and lasting co-morbid resolution  and weight loss maintenance with Duodenal Switch. It has been know for years that a sizable number of patients having the sleeve will experience weight regain requiring conversion to the duodenal switch or the RNY Gastric Bypass. Majority of the patients having gained weight after sleeve, or experiencing the return of co-morbidities after a transient resolution during the their weight loss phase, should only be revised to the Duodenal switch operation in my opinion. The alternative procedures of SIPS and SADI or similar single anastomosis operation with confusing nomenclature should be avoided, since as of the publication of this blog they are still considered investigational by the American Society for Metabolic and Bariatric Surgery (ASMBS) with no long term data.  The only plausible reason for revision of the Sleeve to the gastric bypass (RNY) would be those patients who are experiencing reflux. Felsernreich et.al. demonstrated that 10 years after sleeve gastrectomy  33% were requiring revisions of their sleeve due to weight regain or reflux. 66% needed revision for weight loss and only 34% for reflux. Those patients who have revision to gastric bypass (in their practice all being revised with two exception) had resolution of their reflux however had no sustained weight loss after the revisions. This supports our position that we have had for years that the those patient who had the sleeve and are experiencing weight regain, recurrence of comorbidities inadequate weight loss ahould all be revised to the duodenal switch operation.

Sunscreen

June 27, 2019 3:03 am

Recently there has been some research and concern regarding sunscreen and the chemicals within them. This has led to findings that can be concerning but that need further research.

Post weight loss surgical patients, and in general patients who suffer with obesity, before or after weight loss surgery, have low vitamin D level. This may be caused by a number of factors. One such factor may be the reluctance to get skin exposed to sunlight in order for the bodies natural Vitamin D pathways functioning.

The recommendations are for daily exposure to sun. This not only is critical to the vitamin D metabolic pathways, but also help with bone health, immune function, mood, counteracting depression.

In a recently published online article, concerns were raised that some of the ingredients of some of few sunscreens are absorbed in the blood stream. This is a small study, and as the results indicates, it is not recommending to stop using the sun screens. Be aware of your sun exposure, timing exposure, and the ingredients in your sunscreen.

You can find past blog posts on Vitamin D, Bone health, etc here

Thyroid Medication Absorption And Weight Loss Surgery

June 10, 2019 8:59 am

Question : “Do I have to take higher dose of thyroid medication after the duodenal switch? ”

Answer : “Maybe”

With all weight loss surgical procedures, there may be changes to absorption of medications. It is easily understood why duodenal switch may results in decreased absorption of fat-soluble medication. What is not as clear is the reduction in absorption of other medication with procedures that do not explicitly change the absorption at the level of the small bowel directly.

The research data is all over on this topic. There is published literature that shows improvement in the thyroid function after gastric bypass and the sleeve gastrectomy.  However, the exact mechanism is not completely understood.

There is research that reports “…decreased postoperative levothyroxine requirements.” Other have shows no correlation between the length of the bowel distal to duodenum to absorption of thyroid medication.

With all this confusing data, the best course would be to always “treat the patient and not the lab results.”

If a patients who has been on medications with stable number and symptoms,  suddenly presents with complaints of hypothyroidism after weight loss surgery, it’s possible the medications should be up adjusted even if the thyroid lab values may not be as defining.

   

Osteoporosis Medications, Action and Side Effects

May 25, 2019 3:40 pm

Recently I had a short live presentation on the subject of osteoporosis, osteoporosis medications, and the treatment options of this deteriorating bone condition. A patient who has had a bone scan may be diagnosed with Osteopenia and/or Osteoporosis. This information is usually conveyed by the forms of a Low T score. Both of these indicated demineralization of the bones, and the end result is  worsening of the bone structure. This leads to weaker bones and higher chance of fracture due to stress or trauma.

Treatment options should be approached is a global and systemic fashion. It is critical that the nutritional status is at its best possible and optimized for important healthy bone vitamins and minerals. Low protein needs to be corrected. Special attention should be given to nutrients, minerals and vitamins. These include ProteinCalcium, Magnesium, Vitamin D, and Vitamin K1/K2to name a few.

Healthy bones require ongoing and routine force in the form of exercise to remain health. Just as exercise improves muscle strength, it also improves bone health. Exercise is also critical in improving bone structure and density. Ideally, exercise should be weight bearing and resistance.  Examples include: hiking, walking, jogging, climbing stairs, playing tennis, and dancing. Resistance type exercise is weight lifting and resistance bands.  These exercise work by creating a pull or force on the bone either by gravity, movement or weight.  Always check with your physician before beginning an exercise routine, start slowly and building up to longer periods of time.  The ideal goal would be at least 30 minutes a day, every day, if you are able.

We frequently see patients immediately started on osteoporosis medications without checking or improving some of the nutritional markers noted above or without looking at exercise history. In some case, the medication recommended are contraindicated due to nutritional status.

The medications can be grouped in to those  that help with new bone formation (Anabolic agents) or those that help by suppressing the bone breakdown phase (Antiresorptive agents).

Groups of Medication

 

National Osteoporosis Foundation has an exhaustive list (below) of medications for treatment of Osteoporosis.

The table below outlines the side effects and mechanism of the actions of the common medications used for treatment of  osteoporosis which was published by the University Health News Publication on August of 2014.

Mechanism Of Action And Side Effects

 

With all this information, the few points to remember is that the most important factors in healthy bone structure are the nutritional status Protein, Calcium, Magnesium, Vitamin D, and Vitamin K1 levels.

This is an animation of normal bone Metabolism. It shows how bone structures is taken down and rebuilt continuously. This allows for a healthy bone maintainence as we age. The key is the balance of breakdown (osteoclast) and the build up (osteoblast) activity is regulated. Osteoporosis develops when there is more breakdown that build up.

With permission of Dr. Susan Ott of University of Washington.

Additional information available on her site.

Past blogs on Bone Health.

Gastroesophageal Reflux: Bile Vs. Acid

May 14, 2019 12:52 pm

Gastroesophageal (GE) reflux is the condition when the stomach content are able to “reflux” back thru an incompetent lower esophageal sphincter (LES)  into the esophagus.

Gastroesophageal reflux Disease (GERD) is the clinical condition which is the result of long standing reflux and results in microscopic and visible changes to the inner lining of the esophagus, esophageal mucosa.

GERD is a non descriptive as to the cause of the condition. It only states that the content of the stomach have been irritating the lining of the esophagus on chronic bases. This can be caused by an anatomical abnormality fo the GE junction (Hiatal Hernia), or may be related to disfunction the LES. Other possible causes of the GERD may be infection (H.Pylori) environmental (stress) and dietary (nicotine, alcohol, caffeine, spicy food) in origin.

So far we have not clarified the chemical nature of the the refluxed content.

In Acid Reflux, the relative acid overproduction of acidic secretion and the exposure of the esophageal mucosa is what needs to be addressed. This is accomplished by acid suppression medications, Anti Histamine (H2 blockers) Proton pump inhibitors (PPI) for example.  The physiology, and the mechanism involving this condition is well understood. As a surgeon, we do however see patients who should have had surgical intervention. The initial mode of therapy for a patient with documented acid reflux, and or symptomatic hiatal hernia is placing them on medication. These patients are then recommended to have related upper endoscopy. Patients who do not improve or where deterioration of the esophageal mucosa, presence of precancerous cells, then the patients are referred for surgical intervention.

Bile Reflux, contrary to acid reflux may have very little if anything with the LES. The symptoms experienced by the patient may be as ofter related to the excessive bile in the stomach seen frequently

Bile Reflux Gastritis
Foveolar Hyperplasia- Bile Reflux Gastritis

after cholecystectomy, or in those patients with dysfunctional gallbladder (low EF on HIDA scan).

The treatment of Bile reflux, is Duodenal Switch with without the associated sleeve gastrectomy component in addition to repair of hiatal hernia if present Ann Surg. 2007 Feb; 245(2): 247–253.

PolyCystic Ovarian Syndrome PCOS

September 04, 2018 9:58 am

PolyCystic Ovarian Syndrome PCOS is a complex condition. The exact cause of PCOS is unknown however, it involves hormones imbalance and multiple ovarian cysts, irregular menses, and infertility. In some cases, PCOS can be compounded by diabetes, hypertension and other metabolic conditions. PCOS has been shown to effect approximately 10% of women of childbearing age with symptoms of menstrual abnormalities, poly cystic ovaries, and excess androgen (male sex hormone). PCOS should be diagnosed by ensuring there are no other underlying endocrine issues. There are several associated disease processes that seem to be related to PCOS. These related disease processes are Type 2 Diabetes, higher depression and anxiety, increased cardiovascular risks, stroke, hyperlipidemia, sleep apnea, overall inflammation, and endometrial cancer.

Anatomically, numerous cysts are found on the ovaries. These are usually diagnosed by ultrasound, blood levels of hormones, and symptoms described above.

Poly Cystic Ovarian Syndrome
Poly Cystic Ovarian Syndrome

Bariatric Surgery and PolyCystic Ovarian Syndrome PCOS

Bariatric Surgery can improve PCOS in those individuals with Type 2 Diabetes Mellitus. Further information on weight loss surgery and its effect on PCOS here.