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

People that had SARS-CoV-2 infections may think that they have “natural immunity” and are protected from getting re-infected from this COVID-19 virus. But there are 2 new studies showing evidence that vaccination generates a more vigorous B and T cell (immune memory cells) response than does natural infection. It shows that vaccination is particularly stronger in people with previous SARS-CoV-2 infections.

Researchers evaluated people who were vaccinated with the mRNA vaccine after natural infection and people who were vaccinated but had no prior infection. Memory B cells against SARS CoV-2 were 5-10-fold higher when vaccination followed natural infection than after natural infection or vaccination alone. The most surprising result was that in people who were vaccinated after natural infections, neutralizing antibodies against the beta variant were higher. They were 25 times higher than after vaccines alone and 100 times higher than after natural infection alone. This was amazing since natural infections were almost never with the beta variant and that vaccines don’t target the beta variant spike protein.

Other studies as well have shown similar results. A study in the CDC (Centers for Disease Control and Prevention) Morbidity and Mortality Weekly report shows 2.3 times the number of reinfections with natural immunity compared to breakthrough infections in those who are vaccinated. It is unclear how effective natural infection is against other variants, particularly the Delta variant. This new variant, as well as the lambda variant, may weaken the protection provided by having been previously infected by SARS-CoV-2.

People who have had COVID-19 are advised to be vaccinated. It will very likely offer better protection against symptomatic reinfections, even with the Delta and future variants.

References: Diamond, F. Kavanagh, K. Get vaccinated even if you’ve gotten COVID-19, study suggests. Infection Control Today 2021, Aug 8.

Stamatatos, L et al. mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection. Science 2021 Mar 25; 372: 1413.

Deepti Gurdasani is a British-Indian epidemiologist who is a public researcher at the Queen Mary University of London. This is a part of a thread in which she discusses Long COVID and the implications in the community.

Several studies have put the overall incidence of long COVID between 10-50% of those infected. Scientific consensus is that Long COVID is not just a respiratory disease but a “real” multi-system syndrome that occurs in those infected- predominantly impacting the young. The Office of National Statistics (ONS) data and REACT-1 data compares symptoms post infection among those infected with control groups of those confirmed not to have infection. These are some of the most robust data on Long COVID based on PCR tests through random nationally representative surveys of thousands of people (ONS data 313, 216, and REACT-1 data 508,707 samples).

Here are some highlights:

Most people present with a combination of symptoms and of the 1 million people affected, 2/3rds said it impacted their day-to-day activity. About 400,000 have had persistent symptoms for over 1 year. Sadly this included 9000 children who have been affected for more than a year. Those with the highest risk factors were women, increasing age, smoking, and low income.  There is strong evidence that even those with mild symptoms can have long-term structural brain changes including thinning of grey matter in brain areas related to smell, taste, memory and emotion. The risk of organ dysfunction was 38.9% in those aged 19-49 years. This clearly impacts a large proportion of young people.

So to summarize, long COVID is common- even in young children with mild infection. It usually includes multiple symptoms, that in many, affects day-to-day lives. Remember that children under the age of 12 cannot get vaccinated. Let’s do our part and get fully vaccinated for ourselves, our families (and children) and our community.

Follow the full thread at @dgurdasani1. Other links are Post Acute COVID-19 Syndrome and Survivor Corps

Electronic health records were studied at multiple institutions in the U.K. Researchers estimated the incidence of neurological or psychiatric sequela in 236,000 people with COVID-19 infection. During the 6 month follow-up, 13% were diagnosed for the first time with either a neurological or psychiatric condition with no prior history of these conditions. Another 21% of patients who had prior conditions developed new conditions.

These rates were compared with rates in 342,000 people with influenza and other respiratory tract infections. The incidence of neurological and psychiatric diagnoses were significantly higher in COVID- 19 patients. The most common diagnoses were anxiety (17.4%), psychotic disorder (2.8%), ischemic stroke (2.1%), dementia (0.7%) and intracranial hemorrhage (0.6%).

The most concerning were those whose acute COVID-19 infection caused encephalopathy (defined as delirium or other altered mental states). In those with encephalopathy, the chances of developing mood disorder were 22%, anxiety disorder 22%, ischemic stroke 9%, psychosis 7% and dementia 5%.

This large study demonstrates that various psychiatric and neurological conditions develop with a relatively high incidence in 6 months following acute COVID-19 infection in people with or without previous disorders. We need to look for interventions to address these sequela for post COVID patients. It is not just about surviving this infection, but hoping that you don’t fall into the long-hauler conditions that are so debilitating. One site connecting people with these symptoms that provides support and resources is survivor corps.

It is unknown whether the post COVID mood and anxiety disorders are due to the psychological stress of the illness, or that they are triggered by neuro-inflammation caused by the infection. Regardless of whether it’s the “chicken or the egg”, these symptoms are real and thus far unpredictable as to how long they may last.

Reference: Taquet M et al. Six month neurological and psychiatric outcomes in 236379 survivors of COVID-19; A retrospective cohort study using electronic health records. Lancet Psychiatry 2021 April 8:416.

The question that remains on people’s minds is how effective and long lasting the immunity is from either having had the COVID-19 infection or the vaccine. Now we are starting to get some answers. According to a population-wide study in Australia using data from the SARS-CoV-2 national infection reporting system, the re-infection rate has been low.

Researchers compared the odds of SARS-CoV-2 re-infections of COVID-19 survivors of the first wave (February- April 30, 2020) versus the odds of first infections in the remainder general population (by tracking PCR confirmed infections of both groups) during the second wave (September 1st-November 30, 2020). Out of the almost 15,000 COVID-19 survivors of the first wave and 253,000 infections in the 8.9 million individuals of the remaining general population, only 40 tentative re-infections were recorded.

This shows a relatively low re-infection rate of SARS-CoV-2 in Australia. Assuming that convalescents were exposed to COVID-19 at the same rate as people in the general population during the second wave, reduction in risk for re-infection was >90% which lasted for at least 7 months. Protection against SARS-CoV-2 after natural infection is comparable with the highest estimates on vaccine efficacies. Based on this data, there appears to be considerable protective immunity for at least 7 months after COVID-19 infection and no urgent need for booster vaccinations in COVID-19 convalescents. More well-designed research is needed for improving evidence-based public health decisions and vaccination strategies.

Reference: Pilz S et al. SARS-CoV-2 re-infection risk in Australia. Eur J Clin Invest 2021 April; 51:e13520.

I’ve published many studies linking the gut microbiome to certain health conditions. One of the conditions that has shown significant interest is mood disorders, especially major depressive disorder (MDD). Studies that have linked the gut microbiome to major depressive disorder have been small and have been met with skepticism. A recent study from China may give us more insight into the mechanism by which bacteria in the gut might influence brain chemistry. Researchers collected 311 fecal samples from people with MDD (unmedicated) and from healthy controls. Microbiome researchers were looking for a more precise picture of the organisms present versus a genus level within a batch of microorganisms.

Results found 18 specific bacterial species that were more abundant in those with MDD. They also found 3 specific bacteriophages (viruses that infect bacteria), and 50 fecal metabolites that were significantly associated with MDD verses healthy controls.  The gut bacterial metabolites that correlated with MDD were molecules that are involved in amino acid metabolism. The most important pathways were related to gamma-aminobutyric acid (GABA), phenylalanine, and tryptophan metabolism. These molecules enter the blood from the gut, affect neurochemistry, and have been implicated in MDD.

Researchers point out that GABA, a neurotransmitter in the brain, is made by gut microbes. Fecal levels of GABA and some of its metabolites were decreased in the MDD patients. GABA related microbial genes were also altered in MDD patients suggesting that microbes modulate GABA levels. It is possible that this may dysregulate the function of GABA in the brain, and could lead to depressive symptoms.

Scientists also hypothesize that an increase in certain phyla called Bacteroides could increase inflammation which has been linked to MDD. Also decreased Blautia bacteria which has been shown to have anti-inflammatory effects could contribute to MDD. Other studies have found that when fecal transplanting the entire microbiota of a person with MDD into a germ-free rat, it causes “depressive-like” behaviors in the rat.

Epidemiological researchers have found that many people with irritable bowel syndrome are also depressed. Also those on the autism spectrum tend to have digestive problems, and people with Parkinson’s disease are prone to constipation. Researchers have also noticed people taking antibiotics are more prone to depression compared to those taking antiviral or antifungal medications that leave gut bacteria unharmed.

So what is the mechanism behind the actually pathway from the gut to the brain? Some substances secreted by the gut microbes may infiltrate blood vessels for a direct ride to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Indirect links might also exist. Gut bacteria is so important to proper immune function and studies show that having the wrong mix of microbes can promote inflammation. Microbial products can influence enteroendocrine cells which reside in the lining of the gut and release hormones and other peptides. Some of these cells regulate digestion and control insulin production. They also release the neurotransmitter serotonin which escapes the gut and travels throughout the body. This is where our gut flora might influence weight gain, sleep and how we respond to stress.

It’s crazy to think how much influence our gut has to our mood. Depressed symptoms can influence our diet behavior which can influence our gut characteristics and composition. On the other hand, our bacteria can produce some special metabolites and have a specific pathway that can influence our brain function. More research needs to be done to determine whether any of these pathways are actually causally related to depression. Nutritional psychiatry is a new emerging field that is so exciting. We may be able to target the microbiome through diet (and specific probiotics) which could alleviate some of the symptoms of depression.

This is one more piece of evidence that shows a strong association of microbiome function and mental wellbeing.

Reference: Yang J et al. Landscapes of bacteria and metabolic signatures and their interactions major depressive disorders. Sci Adv 2020 Dec 2; 6:eaba8555.

The Psychbiome