There has been growing interest in the interaction between the gut microbiome (genes of gut bacteria) and medications. Some medications are known to effect the gut in certain ways. For example, antibiotics tend to change the amount and types of bacteria in the gut which can cause side effects such as nausea and diarrhea. The drugs associated with lowering stomach acids such as PPIs (protein pump inhibitors), is associated with an increase in oral bacteria (that’s right…bacteria that’s found in the mouth) and potential pathogenic bacteria in the gut. There are interactions between the gut microbiome and medications.

Researchers studied the effects of 15 drugs on 25 strains of human gut bacteria and found a variety of drug-bacteria interactions. Some bacteria store the drug without chemically changing it while other bacteria chemically modify it to make it more or less bioactive. In other words, the gut bacteria can determine the amount of a drug (or an active drug metabolite) that is available to the body.

The opposite is also true. A particular drug can also affect a patient’s gut bacteria, both the number and function of that bacteria. For example, the build-up of a drug within a strain of bacteria can change the growth rate of those bacteria. Sometimes a drug can even change the molecules that are secreted by bacteria. This doesn’t sound like a big deal until you understand that the molecules can include hormones, neurotransmitters and molecules of inflammation that effect our physiology. There are clearly interactions between the gut microbiome and medications.

The drug variability can be due to either a person’s genetics or due to the person’s gut flora. Association studies have shown changes in the abundance of various gut bacteria in individuals with inflammatory bowel disease, irritable bowel syndrome and colorectal cancer.  This has also been found in other systemic diseases such as cardiovascular, metabolic conditions, autoimmune and psychiatric disorders.

As you can see here, there is a complex bidirectional interaction between commonly used drugs and the gut microbiome. This means that among people who have the same disease, a particular drug can vary greatly in its effectiveness and adverse effects. Perhaps this will help us in finding interventions to modulate the gut microbiome and optimize effectiveness of treatment.

Reference: Klünemann, M et al. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature 2021 Sep; 597:533

Weersma, R et al. Interaction between drugs and the gut microbiome. Gut 2020 Volume 69, Issue 8. gut.bmj.com

It was difficult finding the Top 10 health breakthroughs of 2021 while being inundated with constant breaking news of the COVID-19 infection. Let’s face it….it has been another exhausting year for all of us. The COVID-19 pandemic is still raging and continues to be the biggest topic in health news (as it should be). We are faced with more uncertainty as Omicron has surfaced with it’s 30 mutations and conflicting data on its severity. Let’s see if we can side step this historical pandemic and look for other inspirational discoveries of 2021. Here are your top 10 health breakthroughs of 2021:

10. New Approach for Migraine Treatment: Researchers has discovered a new cause of migraines known as CGRP (calcitonin gene-related peptide), a chemical that nerves use to talk to each other and gets released during migraine. The CGRP blocker drug, Rimegepant has been a lifesaver for many with migraines that have found no relief with other modalities.

9. Treatment for Sickle Cell Disease: This deadly genetic condition causes red blood cells to change into a sickle shape. This can cause obstruction of blood vessels or cause them to burst apart leading to infections and severe organ damage, cutting life expectancy to age 54. New drugs, Oxbryta and Adakveo, have been FDA approved and prevents hemoglobin inside the red blood cells from sticking to each other and forming sickles. Studies have shown significant improvement in fewer episodes of severe anemia and longer life expectancy.

8. First Blood Test for Alzheimer’s Disease: Now there is a prescription blood test called PrecivityAD. It measures proteins linked to amyloid plaque buildup in the brain which is a hallmark of Alzheimer’s disease. This test went public without FDA approval which drew some controversy. But the studies have been impressive showing that the test was 94% as accurate at finding brain plaque as PET brain scans that use radioactive tracer dye.

7. COVID vaccines to the Rescue: The new mRNA technology is one of the biggest advances in medicine that we have ever come across (and at warp-speed!) Expectations of the Phase 3 clinical trials on the mRNA-based vaccine was 50-60% which was hopeful. Instead it was more than 90% effective in reducing the risk of developing severe COVID, hospitalization and death. As you may be concerned that theses vaccines are too “new”, let me remind you that they were already here from decades of study.

6. First Oral Antiviral to Treat COVID-19. Paxlovir is under FDA Emergency Use Authorization for treatment of moderate to severe COVID-19. It is actually 2 drugs taken together. Two tablets of 150 mg Nirmatrelvir and 100mg Ritonavir taken twice per day for 5 days. It is indicated for those with mild-moderate symptoms but are at high risk for progressive disease that could lead to hospitalization or death.

5. Advances in Gene Therapy: Researchers successfully treated a genetic liver disease by injecting the CRISPR gene-editing tool into a person’s body. This gene-editing tool works by using enzymes that cut away portions of DNA that are responsible for DNA mutations and returns them to their normal function. This could pave the way of healing a wide variety pf genetic conditions.

4. New Oral Anti-fungal for Vaginal infections: This is for the 1.4 million women that see their doctor each year in the U.S for vagina yeast infections. This is the first new anti-fungal in more than two decades representing a new class called triterpenoids. This new drug, Brexafemme works by blocking an enzyme that creates a protective coating around Candida Fungi. Without this coating, the fungi quickly die off. The 2-tablet treatment starts working within a few days and stays in the system for up to 2 weeks to help prevent recurrence.

3. First Vaccine for Malaria (and other parasitic infections): Malaria kills about half a million people a year worldwide. A new vaccine, Misquirix, is about 50% effective against severe Malaria. Even though 50% does not sound very effective (compared to the 95% effectiveness of COVID-19 vaccines), it may save those at high risk for severe infection such as the elderly, pregnant women and children who live in countries with high numbers of Malaria cases. You can take preventative medicine before, during and after a trip to  high-risk areas, but many parasites have developed resistance to common drugs used to treat the disease.

2. Treating a Torn ACL without Surgery: The ACL, or anterior cruciate ligament is one of the  most common injuries for athletes and non-athletes. Treatment involves surgery and reconstruction using a piece of bone and tendon from another part of the body or using a donor to rebuild the ligament. Now the Bridge-enhanced ACL Restoration Implant takes the place of that material. It is FDA approved and made of bovine collagen. It is secured in place between the two torn ligaments. The patient absorbs the device and grows new, healthy tissue in its place in a few months.

1. The First At-home Test for COVID-19: The Ellume at-home COVOD-19 test was the first test of it’s kind to get FDA authorization. This allows consumers to check their COVID-19 status without going to the doctor or to a PCR testing site. It is an easy test that swabs both nostrils and gives the result in 15 minutes. It identifies positive cases 95% of the time and negative cases 97% of the time. Since that first test, a new test called BinaxNOW by Abbott has also become a common and accurate COVID-19 antigen home test.

Happy New Year! Wishing you the best of 2022!  May it be a year full of good health, joy and some certainty.

References: Schindler, S, Goadsby, P. Love, T. The New Health Heroes: Life-altering new treatments for heart, mind and more. Medical Breakthroughs 2021. AARP, Oct/Nov 2021.

Temte, J. Coronovirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19. Practice Update. 12/23/2021.

Maldarelli, C., Sohn, R. The Top 10 health and medicine breakthroughs of 2021. Popular Science, Dec 1 2021.

Mastroianni, B. From Vaccines and Gene Editing to Malaria Treatment: The Important Medical Innovations of 2021. HealthLine. Dec 27, 2021.

Can eating a specific food or following a particular diet help prevent or delay dementia caused by Alzheimer’s disease? Many studies suggest that the choices we make in what we eat affects the aging brain’s ability to think and remember. These findings have led to research on general eating patterns and whether they might make a difference.  Studies indicate that inflammatory foods can raise the risk of dementia.

A study looked at the diets of over 1000 people, mean age 71, for an average of 3 years. Dieticians categorized an inflammatory index score based on 3 levels of inflammation: low, intermediate and high inflammatory foods. It is no surprise that the high inflammatory diet category had three times the incidence of dementia than the low category group. Those in the low category diet ate more vegetables, fish and fiber. While those in the high inflammatory food group ate more red meat,  processed meat, alcohol and sugar. Other research has shown that artificial sweeteners, such as aspartame, are associated with risk for stroke and dementia as well. So how does certain foods change our physiology and raise the risk of certain health conditions?

As humans age, the immune system gradually deteriorates, creating a pro-inflammatory state.  This process actually starts even when we are younger but is noted more clearly as we age. This pro-inflammatory state increases the risk of chronic disease, has been associated with cognitive decline and implicated in the pathogenesis of dementia. This process is called immunosenescence. The inflammatory cytokines that promote inflammation reduce brain-derived neurotropic growth factor (BDNF) and create more oxidative stress, increasing the risks for cognitive impairment or dementia. Diet can modulate systemic inflammation.

Changes in the brain can occur years before the first symptoms of cognitive decline. These early brain changes suggest a possible window of opportunity to prevent or delay dementia symptoms. Risk factors for Alzheimer’s that we can’t change are age and genetics. Research has shown that people can control lifestyle choices such as diet, exercise and cognitive training which affects biological mechanisms, such as oxidative stress and inflammation, that underlie Alzheimer’s.

Some other things to consider: perhaps diet works indirectly by affecting other risk factors for Alzheimer’s disease such as obesity, diabetes and heart disease. Secondly, more and more research is focusing on the relationship between our microbiome (microbes or small organisms that live in the digestive tract) and age related conditions that lead to Alzheimer’s.

One diet that continues to to show promise and gets very little criticism is the Mediterranean Diet. This meal plan emphasizes fruits, vegetables, whole grains, legumes, fish and other seafood and healthy fats such as olive oils, nuts and seeds. It has very low amounts of red meat, eggs and sugars. A variation of this would also incorporate the DASH Diet (Dietary Approaches to Stop Hypertension) which can also help lower blood pressure, reduce cardiovascular disease and dementia. Check out the  Mind diet to help you get started.

References:

1. Pase MP, Himali JJ, Beiser AS, et al. Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Stroke. 2017;48(5):1139-1146. https://www.ahajournals.org/doi/10.1161/STROKEAHA.116.016027
2. https://www.practiceupdate.com/content/artificially-sweetened-beverages-strokeand-dementia/52314/62
3. https://n.neurology.org/content/early/2021/11/10/WNL.0000000000012973

Weight gain in middle age is challenging and very common.

I see many women over the age of 40 that are frustrated with their weight. They are eating healthy and exercising, but the extra weight just won’t come off! Some women even decide to “clean up” their diet and hit the gym even harder but still…no change. Weight gain has been said to be nothing more than your body’s chemical reaction to foods. It’s not that you’re eating too many calories or not exercising enough. It comes down to 2 things: hormones and inflammation.

As women go through their middle years, their body composition changes in proportion to fat.

The proportion of fat to body weight tends to increase (more than men), and fat storage begins favoring the upper body over the hips and thighs. In other words, your waistline starts to grow in inches as visceral fat (the fat that wraps around your abdominal organs) pushing out against the abdominal wall.

What we have learned since the mid-1990’s, is that the fat cell is an endocrine organ, secreting hormones and other molecules that have far-reaching effects on other tissues. There are a host of chemicals that link visceral fat to a wide variety of diseases.

While subcutaneous fat produces a higher proportion of beneficial chemicals, visceral fat produces chemicals that are far more harmful. Visceral fat makes more of the proteins called cytokines, which triggers low lying inflammation and is a risk factor for heart disease and other chronic conditions. It also produces a precursor to angiotensin, a protein that causes high blood pressure.

We know that there is a hormonal mechanism that perpetuates middle age weight gain (obesity) through eating high glycemic foods. Foods that have a high glycemic index pack alot of sugar into a small package. High glycemic foods cause a fast rise in blood sugar resulting in insulin release. Highly processed refined carbohydrates are absorbed quickly, increasing insulin levels that can result in rebound hypoglycemia and insulin resistance. These mechanisms increase insulin sensitivity in adipose tissue but create insulin resistance in muscle and brain. Over time, fat accumulates viscerally while less is taken up in the muscle. Your body continues to make more and more insulin which leads to metabolic dysfunction, inflammation, weight gain, fatty liver and plaque development.

Other research by Mengeste and colleagues describes the characteristics of muscle between obese and lean people.

The obese muscle changes its composition to a muscle fiber (type 2) that is less able to utilize sugar for energy. This is because the number and function of mitochondria decline. These muscle fibers fatigue more easily than the dominant type 1 found in lean people. This is where exercise is so important but initially will not result in quick weight loss because the muscles are less able to absorb and burn energy.

What Does This Mean and What Can We Do?

All calories are not the same. Carbohydrates that are refined and have less fiber get absorbed very quickly and trigger hormones that allow the accumulation of fat. This changes muscle fibers and its function, making weight loss and exercise more challenging. So eating less and exercising more just doesn’t work…especially in middle age. High quality food is key.

So what can we do after age 40 (or even after age 35!)

1. Eat more multicolored fiber-rich whole foods
2. Eat more fiber and protein with a carbohydrate to slow absorption
3. Drink a glass of water with 1 tsp of psyllium husks (or any soluble fiber) before meals to help reduce the glycemic index of a meal. Here is a patient handout on glycemic index/load.
4. Do not use artificial sweeteners. They can actually exacerbate obesity
5. Try to sustain good nutritional and exercise habits over time to increase type 1 muscle fibers. These muscle fibers have more mitochondria to help burn sugar and fat while increasing muscle endurance.

References

1. 1. Ludwig DS, Aronne LJ, Astrup A, et al. The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. Am J Clin Nutr. 2021 Sep 13. doi: 10.1093/ajcn/nqab270. Online ahead of print. https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab270/6369073
   2. Mengeste AM, Rustan AC, Lund J. Skeletal muscle energy metabolism in obesity. Obesity. 2021;29(10):1582-1595 https://onlinelibrary.wiley.com/doi/10.1002/oby.23227
   3.  Jovanovski E, Khayyat R, Zurbau A, et al. Should Viscous Fiber Supplements Be Considered in Diabetes Control? Results From a Systematic Review and Meta-analysis of Randomized Controlled Trials. Diabetes Care. 2019;42(5):755-766. https://care.diabetesjournals.org/content/42/5/755.long