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Dear Dr. K; 

Dear Dr. K; 

I’ve modified my diet to include lots of anti-oxidants and I take vitamin E, vitamin A and beta carotene supplements.  Now I’ve recently heard they don’t reduce inflammation.  What’s the truth and, oh by the way, why can’t scientists get things straight? 

Well, first of all, scientists are people and therefore fallible.  But, science itself can be thought of as a ratchet to the truth moving forward one cog at a time.  And the complete truth/understanding may not become apparent early in the process.  Such is the case with free radicals and antioxidants.   

There has been intensive global research on inflammation and aging.  Early on it was discovered that reactive oxygen species and free radicals cause inflammation and speed up aging.  It was only later on that it was realized that amount matters.  This is based on a phenomenon called hormesis, which means small amounts are beneficial and large amounts are harmful.  Or as Friedrich Nietzsche said “what doesn’t kill you makes you stronger”. 

As it turns out small levels of reactive oxygen and free radicals stimulate the production of detoxifying enzymes and repair proteins for our individual cells and most importantly our mitochondria.  Whereas large levels have the opposite effect.   

Inflammation and aging encompass a spectrum of physiologies but mitochondrial function seems to be a lynch pin factor.  By way of reminder mitochondria are our “cellular batteries” providing life and energy for all of our cells through the production of ATP.  It’s hard to conceptualize but every 24 hours our mitochondria produce an amount of ATP equivalent to our body weight.  So, any perturbation of this system can have significant ramifications.  Because our mitochondria are so active they do break down and fall into disrepair.  That is why the detoxifying enzymes and repair proteins generated by low level free radicals are critical to mitochondrial wellness.    

Having too many broken or fragmented mitochondria not only reduces the numerical workforce but also disrupts cell function by another mechanism dubbed “inflammaging”.  Inflammaging owes its existence to our mitochondria‘s ancient bacterial origins (yes, our mitochondria are due to cells co-opting bacteria internally).  As the mitochondria spill their “bacterial origins” our immune systems mistake these fragments for actual bacterial invaders and attack the cells.  This is why low levels of reactive oxygen are critical to stimulate repair of mitochondria before this occurs.   

Thus, the “Goldilocks” niche of allowing some reactive oxygen for its goodness (all your supplements can interfere with this) but not having too much reactive oxygen (which can be accomplished through healthy diet and exercise).   

Immune Memory Cells 

Immune Memory Cells 

Scientists at McMaster University in Canada and at Mount Sanai in the US have co-discovered the cells that remember an allergy.  The Canadians call it MBC2 while the Americans call it a type 2 Memory B cell.   

B cell refers to a type of lymphocyte critical to immune function.  B cells are the factory for producing immune proteins called immunoglobulins (Ig’s).  Ig’s have a finite life span, but the B cells are much longer lived.  This is important in terms of providing for long-term immunity.  It’s our memory B cells that keep producing Ig’s (AKA antibodies) for all the illnesses we have caught and for all the vaccines we have received.  IgG is especially important in its role of providing durable immunity.   

IgE is the immune protein that causes allergy.  When B cells switch from making IgG (the protective antibody) to making IgE (the allergic antibody) it’s called an isotype switch.  You might ask why in the world would our B cells change from helping to harming?  As it turns out, other than causing allergy, IgE attacks parasites.  Our distant human ancestors all had one or another parasite in their GI tracts.  So, we evolved as a species to have a protective mechanism for this problem.  Fast forward to proper sanitation, safe drinking water and universal footwear and the worms are gone.  So now the IgE is segued to causing allergy.   

Although many people find that their allergies improve over time, many do not.  Peanut allergy is particularly known to be a persistent allergy.  So, the researchers used peanut allergic individuals to find these new memory B cells that weren’t found in non-allergic people.   

It is known that RNA (ribonucleic acid) instructs the B cells to switch from IgG production to IgE.  It does this through a protein called JAK (Janus Kinase).  So, new research is targeting this JAK signaling to see if the long-term memory can be switched off. 

Islet Cell Transplant 

Islet Cell Transplant 

The FDA has recently approved the first pancreatic islet cell transplant for some type I diabetics.  By way of clarification, type I diabetes is due to loss of the pancreatic islet cells and therefore a lack of insulin.  Whereas; type II diabetes is due to insulin resistance because the islet cells are over producing insulin due to obesity.   

Most type I diabetics can be treated with insulin, either by injection or continuous infusion.  But in a small minority safe control cannot be established with insulin.  It is this group of fragile diabetics where the transplant has value.   

The islet cells are obtained from a single deceased donor pancreas and infused into the portal vein of the liver.  Since they are from an unrelated donor, immunosuppressant drugs are required as in other organ transplants.  So far, the procedure has had long term (>5 years) success in only 1/3 of recipients.  But the concept is a novel one and improvements are likely to occur.   

Immune & Nervous Systems Interact 

Immune & Nervous Systems Interact 

Twenty years ago, if someone had said that the nervous system and the immune system interfaced with one another I probably would have scoffed.  I would have done so because with that era’s science I would have found it hard to conceive how brain and nerve cells could control individual immune cells and protein molecules and vice versa.  Boy, I would have been very wrong. 

With the sophisticated molecular biology developed over the past five years or so scientists have a new understanding of this interplay. 

Our immune systems protect us from infections and work to heal damaged tissue after infection or injury.  New science has come to realize that the nervous system and immune system work in concert to achieve these goals.  Our sensory nerves detect injury, infection and inflammation which results in a signal of pain and/or itch.  In fact, direct stimulation of peripheral sensory nerves can drive inflammatory changes in the skin.   

Our immune cells have receptors for numerous neurotransmitters (chemicals released by nerve endings) that allow direct communication between the nervous and immune systems.  And, as it turns out the immune cells can also produce neurotransmitters that communicate with nerve cells.  Depending on which neurotransmitter is released it can either activate or suppress the immune response.   

The immune to nerve communication can lead to a diverse array of unwanted symptoms: amplification of the itch sensation from eczema and hives, hyperresponsiveness of the airways in asthma, loss of sense of smell with nasal allergy and dysphagia (impaired nerve controlled esophageal motion) in eosinophilic esophagitis.   

Now that this interplay is understood, scientists are busy doing research to find ways to modify things in a favorable way to better treat cancer, allergy, autoimmune diseases and infections.   

Dear Dr. K; 

Dear Dr. K; 

I’ve lived in Florida my whole life and had tons of mosquito bites, but now they are swelling way more and lasting a week or longer.  What’s up with that? 

It means it’s time for you to leave Florida and lessen our traffic jams….no, just kidding.  Most likely it means you have developed an allergy, but a rare cause for strong reactions to arthropod bites is as an early sign of leukemia or myeloma.   

Mosquitos have been around for over 100 million years (specimens found in amber date to 100 million years ago).  Homo sapiens are a new addition to the planet.  Scientists estimate that there have been 110 billion humans and that half of us have died from mosquito borne diseases.   

A few additional facts about mosquitos are cogent.  Only female mosquitos bite.  They need blood to nourish their eggs and larvae.  Male mosquitos eat pollen.  When a mosquito bites us, she uses six mouth parts.  There are two serrated “knives” that cut our skin, then two “retractors” to open the rent and one retractable “sucking needle” to extract blood and one “saliva needle” to insert the saliva.   And the saliva she injects as an anti-coagulant contains proteins that can lead to the development of allergy.  In experimental models, the best way to induce an allergic reaction to a substance is by discreet but intermittent exposure.  So, if that is what has happened to you over time, your immune system has “learned” to dislike the salivary protein.  Depending on the severity of the reaction, various therapies can be used.  Oral antihistamines help.  Topical steroid (either OTC or prescription) applied quickly and under occlusion (a band aid makes the steroid penetrate better) works even better.  For more severe cases an allergy shot for mosquito can be done.   

On a different note, in terms of mosquito borne diseases, malaria has garnered the most attention.  Several standard types of vaccine strategies have been tried with modest and mixed results.  More recent trials with a monoclonal antibody are looking much more promising.   

Mosquitos do bite some individuals more than others.  Women are more attractive to mosquitos than men.  Pregnant women even more so, as during pregnancy women exhale 20% greater carbon dioxide than non-pregnant women.  Mosquitos are attracted by carbon dioxide, type O blood, scents/perfumes, certain skin bacteria and bright clothing.  Beer also seems to attract them.   

Dear Dr. K;

Dear Dr. K;

I recently underwent food allergy testing at the behest of my gastroenterologist to see if food allergies are causing or contributing to my irritable bowel syndrome.  It turns out I’m allergic to five foods.  My question is how do I determine if all five are causing my symptoms or just one or two?

That is a great question.  The guidelines I’m going to share with you were worked out in clinical research units.  In these settings patients are kept in a controlled environment (typically a hotel appended to the university hospital) and avoid the implicated (food allergy test positive) foods for two weeks.  It seems to take this long to fully “clean the system”.  Then, one food at a time is re-introduced.  In the research setting this is done double blinded and placebo controlled by putting the food to be tested inside gel-caps.  On a given day the patient may receive a placebo or an actual food.  Now, obviously this is a very tedious and protracted protocol.  But it has led to some basic rules to be used at home.

So, first of all, you need to avoid all five foods at the same time for two weeks.  If food allergy is causing your IBS, you will feel better at the end of two weeks. 

Then start adding a single food. You should have this food in “a usual portion size” and have it at least three days in a row.  If you have “tummy troubles” the very first day it could be due to the food or serendipity.  So, you need to repeat the experiment to verify. 

Now here is the hard part.  If you have symptoms you need to go back to the elimination diet until you feel well again before you try the next food.  Unfortunately, this could take up to two weeks again.  But you need a symptom reduced baseline to have clarity. 

Once you’ve tested all the foods there is another step you might need to take.  But this is necessary only if all the individual tests were negative.  This step involves testing food combos.  By way of example let’s say you tested positive to cheese, tomato and wheat.  Tested individually: no issue.  But tested together might reveal synergism.  So, pizza would be a mechanism to test all three.  Good luck, be patient. 

Omalizumab for Food Allergies

Omalizumab for Food Allergies

The FDA recently approved omalizumab (Xolair) to treat patients with food allergy including children as young as one year.  The approval came from several research trials including one recently published in the New England Journal of Medicine (NEJM) that was conducted at John’s Hopkins.  This particular study looked at allergy to peanut, cashew, egg, milk, walnut, hazelnut and wheat.  In the case of peanut allergy 67% of the test patients were able to consume 600 mg of peanut (equivalent to four peanuts) without adverse symptoms. 

The current recommendation is to only consider this therapy in people with severe (anaphylactic) food allergy.  In addition, the intent is not to enable ongoing ingestion of the food but to protect against anaphylaxis due to accidental exposure.  

An accompanying editorial in the NEJM was a bit of a devil’s advocate pointing out that the treatment is not curative but only works as long as the medication is continued.  It further argued that avoidance is still the lynch pin of therapy in severe food allergy.

The editorial did point out the potential safety net for children who otherwise run the risk of anaphylaxis from accidental exposure. 

That’s Bananas!

That’s Bananas!

By:  Sasha Klemawesch, MD

If I asked you to tell me one fact about bananas, you’d probably cite how rich they are in Potassium.  And you wouldn’t be wrong.

But, in addition to having approximately 10% of your daily value for potassium, they also contain about 10% of your daily needs for Magnesium, Vitamin C and Fiber.  While potassium is great for lowering blood pressure, maintaining muscle (including heart muscle) strength, and avoiding certain types of kidney stones, foods with high potassium content may also be slightly radioactive!

This is because included in their potassium stores is a tiny bit of Potassium-40, which is a radioactive isotope. But don’t worry, there is not a human being out there – or monkey for that matter – who could possibly consume the volume of bananas necessary to incur any harm from them (it’d take like 20 million to reach a dangerous dose).

There is enough of the isotope however that you wouldn’t be allowed to bring bananas into a nuclear power plant due to their potential to trigger the (highly sensitive) alarms.  So, while you may not need to worry about getting radiation poisoning from bananas, if you have a latex allergy; you should probably avoid them. It seems unusual for a man-made material and a natural fruit to be related, but latex actually shares several allergens in common not only with bananas, but also avocados and kiwis.

Other groups who should avoid bananas are male mice. If you are one, #1 congratulations on becoming literate enough to read this! and #2, you have probably already realized that you feel stressed out when you smell banana pudding. This is because pregnant female mice’s urine contains n-pentyl-acetate; the same compound that imparts bananas their distinct odor. It’s also the hormone pregnant mice secrete in

order to repel males, thereby preventing them from eating their babies.

Lastly, if you still enjoy listening to CD’s, and you have run out of toothpaste to fix your favorite one’s scratches, try rubbing a banana peel over the defect. The oils in it will do the same thing the toothpaste does and repair the skip!

Plastics

Plastics

There is a memorable scene from the movie The Graduate where Ben (Dustin Hoffman) is taken outside at his college graduation party by a friend of his fathers’.  The friend says (regarding Ben’s future) “I have just one word for you: plastics”. 

Fifty years ago, plastics seemed to be a boom in terms of both convenience and commerce.  Now, plastics are doom in terms of environmental harm and human health.  Once plastics are released into the environment (soil and water) they gradually degrade, leading to the formation of micro plastics (smaller than 5mm) and nano plastics (smaller than 1000 nanometers).  These in turn can enter the human body through ingestion, inhalation and skin absorption.  Ninety five percent of Americans have micro/nano plastics in their bodies.  The health consequences are myriad:  interstitial lung disease, increased rates of premature birth, asthma, certain types of cancer, and liver and kidney disease. Now a new concern has recently been reported by scientists at the University of Campania in Italy regarding cardio vascular events.  Their research found 60% of their patients having surgery to remove arterial plaque had micro/nano plastics (MNP) in the plaque itself.  More distressing was that the 60% with MNP had much higher risk for heart attack, stroke or death in the ensuing 34 months than the 40% who did not have MNP. 

What to do?  Unfortunately making a personal choice to use less plastic will not protect individuals since it is primarily the degradation of discarded plastic that is the prime mover.  It will take a global initiative to make a difference. 

Aw, Nuts! By: Sasha Klemawesch, MD

Aw, Nuts! By: Sasha Klemawesch, MD

Conventional wisdom for decades has been to avoid nuts and seeds if you have diverticulosis; however official Gastroenterology literature now says otherwise. Actually, it has for some time, but old habits die hard, and anecdotal rumors still heavily cloud the discussion both in the medical community and among lay people. While it’s not surprising that patients’ impressions may be skewed by rampant Reddit forums on the subject, doctors should be aware of the change in recs, seeing that literally hundreds of studies (more than 300 in the past decade) exist evaluating a variety of dietary effects on diverticular disease. Many of those specifically focused on seed and nuts, and none of them showed any increased harm or risk. The one diet that was affiliated with diverticulitis bouts? No surprise here: “Standard American Fare.” (fried foods, red/processed meats, heavily refined grains, sweets and high fat dairy products). I personally think a big reason why those are correlated with worse outcomes in diverticulosis is that they are all so constipating; and avoiding straining and incorporating fiber and hydration into your diet has long been known to be beneficial (both for diverticulosis as well as in people w/o it).

Now speaking of trying to turn the cruise liner that is diverticulitis management…. Antibiotics. The American Gastroenterology Association has had data out for years showing that we only started treating diverticulitis with antibiotics because “that’s what they always did.” When docs first started doling out Cipro/Flagyl to everyone, it wasn’t based on any scientific trials or evidence, it came more from a logical, hypothetical theory and resultant trial and error approach, and then got passed down from generation to generation. But we now have actual research data showing that uncomplicated diverticulitis in an otherwise healthy patient is more of an InFLAMMatory process, not an InFECTious one, and therefore treatment should include anti-inflammatories, not antimicrobials. Myself being a huge proponent of antibiotic stewardship, I love this change in practice, but it has been pulling teeth to get patients to accept it, and even to change the minds of my fellow colleagues; many of whom say “yeah, I heard about that literature, but I still cover them.” (meaning they prescribe them antibiotics) …  Cut to 4 days later when I see the patient back for their even worse diarrhea due to the antibiotic side effect. Now certain patients and certain cases (i.e. those w abscesses or perforations), still do need antibiotics, but your run-of-the-mill mild case, those do not.

I know many of you will have a hard time *stomaching* this news, so here is a high-quality source for you to check out and verify that I’m not blowing smoke up your behind (sorry couldn’t resist two GI tract puns) just copy this into your search bar:  10.1053/j.gastro.2020.09.059