The Wannabe Mayor And His Spokesperson, Unmasked

Graves’ disease: Causes, symptoms and treatment
10 July 2019 | Category: Ear Nose Throat Print
Share
Tweet
Share
WhatsApp
25SHARES

Graves’ disease is an autoimmune disease causing excessive thyroid hormone release from thyroid gland – hyperthyroidism. As thyroid hormones affect many different body regions, there is a broad range of symptoms of Graves’ disease, and these significantly affect your daily life. It is frequently seen in young adult women. It may cause symptoms such as palpitation, chest pain, shortness of breath, sweating, diarrhea, concentration problems and irritability. If left untreated, it may result in death due to development of certain disorders. The main goal of treatment is to prevent the excessive thyroid hormone production and reduce the severity of symptoms. It can be controlled using anti-thyroid medications. Moreover, it can be cured using radioactive iodine treatment and surgical methods.

Table of Contents

What is Graves’ disease?
Causes of Graves’ disease
Symptoms of Graves’ disease
Diagnosis of Graves’ disease
Treatment of Graves’ disease
Herbal treatment of Graves’ disease
Nutrition in Graves’ disease
Health problems from graves disease
Recommendations for Graves’ patients
What is Graves’ disease?
Graves’ disease (toxic diffuse goiter) is a disease characterized by excessive hormone release from thyroid gland due to immune system cells attacking the body’s own cells. It causes thyroid gland enlargement, i.e. Goiter. It is seen 4- to 5-fold more in women than men. Hyperthyroidism is the most frequent cause. It can be seen at all ages; however, it is most commonly seen between the ages of 20 and 40.

Thyroid gland is a hormone-secreting endocrine gland placed on the anterior-middle part of the neck. It resembles a butterfly. It is a vital organ which ensures a balanced and regular functioning of many important organs and systems such as the heart and the brain. Over- or under-functioning of the thyroid gland leads to many problems in the body. Excessive hormone production by an over-functioning thyroid gland is called ‘hyperthyroidism’.


Causes of Graves’ disease
Our immune system protects us against possibly detrimental organisms such as bacteria and viruses. In genetically predisposed individuals, immune system cells attack and damage certain organs as if they are detrimental organisms, and the reason for this is not exactly known. Diseases occurring via this mechanism are called autoimmune diseases.



Graves’ disease is also an autoimmune disease seen due to immune cells attacking the thyroid gland. In this disease, your immune system produces some antibodies called thyroid stimulating immunoglobulins (TSIs). These antibodies lead to excessive thyroid hormone production that is more than the body’s need. This results in hyperthyroidism.


Risk factors for Graves’ disease
Genetic: It is more frequent in individuals with familial history of Graves’ disease.
Sex: It is more common in women than men.
Age: It is frequently seen at younger and middle ages.
Presence of another autoimmune disease: It is more common in individuals with autoimmune diseases such as type 1 diabetes or rheumatoid arthritis.
Emotional and physical stress: Stressful events or illnesses may trigger the development of Graves’ disease in genetically predisposed individuals.
Tobacco: Smoking increases the risk by affecting the immune system. Furthermore, in Graves’ patients who are smokers, the possibility of disease-induced eye involvement is higher.
Medications: It may occur due to the use of medications such as amiodarone and alemtuzumab.

Symptoms of Graves’ disease
Ophthalmopathy (eye involvement)
Chest pain, palpitation
Weight loss despite increased appetite
Anxiety, restlessness, irritability
Sleeplessness, concentration problems
Intolerance to heat, excessive sweating
Shortness of breath, labored breathing
Diarrhea
Menstrual irregularity
Muscle weakness
Hair loss
Shaky hands
Sexual function disorder

In case of Graves’ disease-induced eye involvement, the eyeball appears like it is placed outwards. Eye dryness, pain, photosensitivity and double vision may be seen. Eye movements become difficulty. Blindness may be seen due to the involvement of optic nerve

Diagnosis of Graves’ disease
The diagnosis is made by medical history, physical examination, laboratory analyses and imaging methods.

Medical history: presence of any co-existing condition, medication use, smoking status, and familial history of the disease is questioned.
Physical examination: The size of the thyroid gland, the presence of pain and temperature increase is checked by palpation. Additionally, presence of nodule (lump) may be checked. The heart and the abdomen are checked by auscultation using stethoscope. The hands are examined for the presence of shaking. Eyes are also examined in detail.
Laboratory tests: Hormone levels indicating thyroid dysfunction including thyroid stimulating hormone (TSH), free T4 and T3 are checked. Moreover, levels of thyroid autoantibodies which may increase in Graves’ disease are also checked.
Imaging methods: The structure of the thyroid gland is assessed using thyroid ultrasound, mainly for the presence of nodule. US-guided sampling may be performed when necessary.
Radioactive iodine uptake test: It is the radioactive form of the iodine taken with food. It is taken orally in liquid or capsule form. As iodine is used by thyroid gland in the body, it is transferred to thyroid gland via blood. After the iodine is taken, body images are taken using special cameras at certain intervals. Thereby, the amount of iodine uptake by the thyroid gland or the presence of non-thyroid iodine accumulation is checked. The use of certain medications which may affect the test result is interrupted before the procedure. Some foods including seafood should not be consumed. It is used for diagnosis and treatment.

Treatment of Graves’ disease
Graves’ disease can be controlled by a successful treatment using proper methods. The goal is to reduce the excessive thyroid hormone levels and protect the body from the effects. Therapeutic options may vary based on the co-existing conditions and being pregnant. Medical treatment, radioactive iodine treatment and surgical treatment can be used.

Medical treatment of Graves’ disease
Beta-blocker medications: They are used for the symptoms including palpitation, high blood pressure, shaky hands and irritability caused by excessive thyroid hormones. The beta-blocker medications in use include propranolol and atenolol. They provide symptom relief until the hormone levels return to normal.

Anti-thyroid medications: They show their effect by reducing the thyroid hormone production. Methimazole and propylthiouracil are used for this purpose. They do not provide cure and their effects are not permanent. Due to the presence of previously synthesized hormones, their effects start late. Propylthiouracil is the one with the fastest onset of action and with the least amount crossing placenta. As methimazole is detrimental to the fetus especially in the first trimester, propylthiouracil is used in pregnant and breastfeeding women. The most common side effects include skin rashes and itching. They may cause infection by decreasing the levels of immune cells of the body, and bleeding by decreasing the level of platelets. Therefore, regular blood analysis is required. They may rarely cause liver failure and jaundice.

Radioactive iodine treatment
The thyroid gland gets damaged by radioactive iodine via oral route, thereby, excessive hormone release can be reduced. The amount of the iodine used is more than the amount used for diagnosis. It can be used in inoperable patients who are not adequately responding to treatment. It must definitely not be used in pregnant and breastfeeding women.

Thyroid gland shrinkage is usually seen a few weeks to a few months after the treatment, and the complaints gradually decrease. The most important side effect is the under-functioning of the thyroid gland due to excessive damage.

Treatment of ophthalmopathy
The first step is to treat Graves’ disease. In addition, cortisone treatment may be initiated. Eye drops can be used and eyes can be closed using dressing to prevent dryness. Sunglasses can be used to reduce photosensitivity. Sleeping with head elevated helps reduce both dryness and swelling. Surgical procedures can be used when necessary.


Surgical treatment for Graves’ disease
Pregnant women, women who are planning to get pregnant early after treatment, younger individuals, patients with moderate-to-severe ophthalmopathy (especially who are smokers), and patients who cannot tolerate antithyroid medications are treated surgically. In addition, surgical treatment is considered if the thyroid gland enlargement is severe to the extent of damaging the surrounding structures. T

hyroid hormone levels are returned to normal using medical treatment before the operation. Based on the hormone levels and the patient’s complaints, total or near-total thyroidectomy may be performed.

Hormone levels are checked at frequent intervals after treatment, and in case of deficiency, external thyroid hormone supplement might be initiated. Bleeding may occur early after the operation. The most important possible side effect is hoarseness.

How long does the treatment of Graves’ disease take?
The risk of recurrence of Graves’ disease is high with treatments shorter than 6 months using antithyroid medications. In this respect, the average treatment duration is 13 months (1- to 2-year). The rate of disease recurrence 1 to 2 years after the medication is discontinued is around 40-80%. The medication is used temporarily (4 to 8 weeks) to prepare the patient for operation. Thyroid hormone levels should be checked at frequent intervals after the medications are discontinued.

Thyroid hormone levels return to normal within 2 months with radioactive iodine treatment. They stay within normal levels for 6 months in 50% of the patients. Over- or under-functioning of thyroid gland may be seen in other patients. The risk of an under-functioning thyroid increases every year.

Beta blocker medications are used until symptom relief.


Herbal treatment of Graves’ disease
As herbal treatment methods may lead to side effects especially in individuals using medications and who have co-existing conditions, you should consult with your doctor before using herbal treatment methods.

Medicinal herbs good for Graves’ disease
In animal studies, certain herbs including Melissa plant (lemon balm), St. John’s wort, throw-wort, club moss have been demonstrated to be effective in hyperthyroidism by reducing the levels of thyroid hormones via various mechanisms. However, human studies on these herbs are lacking, thus, the evidence is insufficient.

Moreover, as they affect the thyroid hormone levels, they may cause changes in other hormones related with the thyroid gland. Therefore, they should only be used within a doctor’s knowledge or if recommended by a doctor.

Nutrition in Graves’ disease
Graves’ disease cannot be treated by only dietary changes nor the disease development can be prevented. However, dietary changes may help with the conditions induced by Graves’ disease including weight loss and bone thinning. It should be remembered that effect of each food is not same for every person.

Vitamin D: Individuals with Graves’ disease should consume foods containing vitamin D, and if necessary, use vitamin D supplements. Foods including eggs, mushroom, salmon may help prevent bone thinning which may be caused by Graves’ disease.
Calcium: Dairy products including milk, cheese and yogurt should be consumed for calcium supplementation. They contribute bone strengthening.
Magnesium: It is possible to increase calcium absorption by magnesium by consuming foods rich in magnesium such as avocado, dark chocolate, almond and legumes.
Selenium: A study performed in regions with mild selenium deficiency has detected that selenium treatment at a dose of 100 microgram given twice a day for six months improves eye manifestations and the quality of life. Therefore, especially patients with eye involvement may prefer foods rich in selenium such as seafood, egg, cereal and dairy products.
High-energy foods: As muscle weakness and thinning may be seen due to this disease, foods rich in protein and energy such as chicken, turkey, beans and hazelnut should be consumed.
Caffeine restriction: Consumption of foods and beverages containing caffeine such as coffee, tea, coke and chocolate should be restricted. Because caffeine may exacerbate the symptoms of anxiety, irritability, palpitation and weight loss caused by Graves’ disease.
Iodine: Iodine is a necessary substance for thyroid hormone synthesis. Adequate dietary iodine intake is necessary. Iodine deficiency may result in thyroid gland enlargement and iodine excess may result in hyperthyroidism. Therefore, you should consult with your doctor about the amount of iodine to be consumed.
Health problems from graves disease
Graves’ disease and hyperthyroidism
Hyperthyroidism develops due to excessive thyroid hormone release in Graves’ disease. One of the most common reasons of hyperthyroidism is Graves’ disease. One goal of the treatment of Graves’ disease is to return the hyperthyroid state to euthyroid state.

Graves’ ophthalmopathy
It is the involvement of the eyes in Graves’ disease. It is mostly seen in Graves’ patient who are also smokers. Patients with Graves’ ophthalmopathy must definitely quit smoking.

Symptoms including burning eyes, watering of eyes, photosensitivity, blurred vision, eyelid retraction, swelling and redness, eye inflammation, abnormal eyeball protrusion, being unable to completely close eyelids during sleep, headache and double vision may be seen. Eye movements become difficulty. Blindness may be seen due to the involvement of optic nerve.

Graves’ dermopathy (pretibial myxedema)
It is seen in approx. 5-15% of the patients. It is characterized with non-pitting swellings on both sides of the extremities and red-orange flaky skin. It may cause itching and pain. Sometimes, it is also possible that there is no sign or symptom. It is mainly seen on tibial area, but also on the dorsum of the foot, back, neck and ankles.

Thyroid storm
It is a rare, however, a life-threatening condition if left untreated. It’s frequently seen in Graves’ disease. It is an emergency seen due to previously-stored thyroid hormones being release into blood. Symptoms include fever, nausea, vomiting, diarrhea, palpitation, heart failure, and mental fog.

Beta-blocker medications and anti-thyroid medications are used for symptom alleviation. Cortisone treatment might be necessary in severe cases.

Heart diseases
If left untreated, Graves’ disease may result in cardiac rhythm problems, cardiac muscle functioning and structure problems, and heart failure.

Bone thinning
Excessive thyroid hormone blocks calcium entry into the bones and impairs bone structure. If left untreated, Graves’ disease results in bone fragility and weakness.

Graves’ disease and pregnancy
Graves’ disease is detected in less than 1% of all pregnant women. If a woman with Graves’ disease gets pregnant, it may affect both the pregnancy and the mother’s health. Pregnancy may trigger Graves’ disease in some women. During pregnancy, Graves’ disease increases the risk of abortion, premature delivery, toxemia of pregnancy, heart failure in mother; and the risk of thyroid disease and low birth-weight in baby.

If you are genetically predisposed or if you have Graves’ disease, you should consult with your doctor when planning pregnancy. You should be sure that hyperthyroidism is under control. For medical treatment during pregnancy, propylthiouracil should be used instead of methimazole. Graves’ disease usually tends to improve spontaneously in the 2nd or 3rd trimester. Medications might even be stopped in many patients.

Radioactive iodine treatment cannot be used in pregnant or breast-feeding women. Pregnancy must be planned at least 6 months after radioactive iodine treatment.

Recommendations for Graves’ patients
Follow your doctor’s treatment recommendations.
Do not miss your follow-up visits as your thyroid hormone levels may change very frequently. As the medications may have significant side effects, return for regular blood tests.
As stress may trigger Graves’ disease, try methods to overcome stress. You can get support from your family and friends.
As smoking may exacerbate ocular signs, you must absolutely quit smoking.
In case of eye involvement, wear sunglasses to protect your eyes from the sun.
You can use synthetic tear drops to prevent eye dryness.
Sleep with head elevated to decrease the edema around the eyes.
Hormone levels may increase greatly and thyroid storm may occur. In case of sudden-onset mental fog, fever, palpitation and shortness of breath related with this entity, seek emergency medical help. For more: >>> Graves’ disease
Resources and References:

Oncology dietitians rarely ask cancer patients about food insecurity, study finds

14

1

Share

Email

Home
Oncology & Cancer
Home
Health
FEBRUARY 11, 2022

Oncology dietitians rarely ask cancer patients about food insecurity, study finds
by Sharita Forrest, University of Illinois at Urbana-Champaign

Credit: CC0 Public Domain
Although studies suggest that many cancer patients experience food insecurity, few oncology dietitians routinely ask them if they are having problems affording or obtaining food, new research has found.

Despite awareness that many cancer patients are food insecure, most of the 41 registered dietitian nutritionists interviewed by researchers at the University of Illinois Urbana-Champaign said they did not use a validated tool to screen patients for it.

The dietitians' estimates of the prevalence of the problem varied widely, from less than 20% to more than 50% of their patients. The participants worked in various types of clinical settings, including outpatient cancer treatment centers and inpatient units at hospitals in urban, suburban and rural locales across the U.S.

Just two of the dietitians in the study reported using a validated screener, while four additional dietitians reported using other tools, such as screening questions developed by the local food bank or questions recommended by a professional organization for oncology nutritionists.

"This study highlights the need for developing education and training opportunities for oncology registered dietitians that will enhance their knowledge of food insecurity as well as their ability to screen for and address it with their patients," said Anna Arthur, the senior and corresponding author of the study who was then a professor of food science and human nutrition at the U. of I.

She is currently a professor of dietetics and nutrition at the University of Kansas Medical Center.

"Oncology patients face a number of barriers and burdens that increase their risks of food insecurity and malnutrition," said Amirah A. Burton-Obanla, a graduate student in nutritional sciences at Illinois and the first author of the study, published in the Journal of the Academy of Nutrition and Dietetics.

"They may be sick from the disease and treatment side effects. Many patients experience debilitating fatigue that prevents them from working and hinders their ability to follow dietary recommendations, prepare food and eat."

Some of the dietitians reported that food insecurity was more prevalent among certain populations, such as elderly patients and those diagnosed with cancers of the head and neck or gastrointestinal tract.

The burdensome costs of cancer treatment and nutritional products can be obstacles for patients as well.

"Patients with lower incomes may be unable to afford the recommended nutritional supplements that could help them get optimal nutrition during treatment," Burton-Obanla said.

One of patients' greatest barriers to obtaining needed food was a lack of transportation, study participants said. Patients living in rural areas and those who lacked family members or friends who could provide rides or assistance with shopping or preparing meals were likely to be at greater risk of food insecurity.

The few dietitians who did ask their patients if they were food insecure said they used various strategies to assist patients with obtaining food or transportation, such as connecting them with Meals on Wheels and other meal services, food pantries, government benefits and grants that provide gas cards and bus tokens.

Despite these efforts, most of the dietitians felt they had little control over their patients' food security.

"The quality of cancer survivors' diet is essential to their overall health, quality of life and survival," said Brenda Koester, the associate director of the Family Resiliency Center at the university and one of the co-authors of the study. "The inability to obtain adequate or nutritious food may lead to malnutrition and impact patients' tolerance and response to oncology treatment, increasing their risks of cancer recurrence and mortality."

With the number of cancer survivors expected to increase to more than 20 million by 2026, there is an urgent need to address food insecurity in this population, the authors wrote.

"Currently, there are no guidelines or recommendations on assessing oncology patients' food security status, but the findings suggest there's a need to do so using a validated screening tool," Koester said. "Implementing routine screenings as standard care in oncology settings would enable dietitians, potentially in collaboration with social workers and other health care providers, to identify food-insecure cancer survivors and develop early intervention strategies."

U. of I. scholars who co-wrote the study are Barbara H. Fiese, the co-director of the STRONG Kids 2 program and a professor emerita of human development and family studies; research specialist Stephanie Sloane; and Craig Gundersen, then the Soybean Industry Endowed Professor of Agricultural Strategy.

9

Share

Email

Home
Neuroscience
FEBRUARY 11, 2022

Researchers find new clues in the brain linking pain and food
by Kelsie Smith Hayduk, University of Rochester Medical Center

Credit: Pixabay/CC0 Public Domain
It has long been known that there is an association between food and pain, as people with chronic pain often struggle with their weight. Researchers at the Del Monte Institute for Neuroscience may have found an explanation in a new study that suggests that circuitry in the brain responsible for motivation and pleasure is impacted when someone experiences pain. "These findings may reveal new physiological mechanisms linking chronic pain to a change in someone's eating behavior," said Paul Geha, M.D., lead author on the study published in PLOS ONE. "And this change can lead to the development of obesity."

Finding pleasure in food comes from how our brain responds to what we are eating. In this study researchers were looking at the brain's response to sugar and fat. Using a gelatin dessert and pudding, researchers altered the sugar, fat, and texture of the foods. They found that none of the patients experienced eating behavior changes with sugar, but they did with fat. Those with acute lower back pain who later recovered were most likely to lose pleasure in eating the pudding and show disrupted satiety signals—the communication from the digestive system to the brain—while those with acute lower back pain whose pain persisted at one year did not initially have the same change in their eating behavior. But chronic lower back pain patients did report that eventually foods high in fat and carbohydrates, like ice cream and cookies, became problematic for them over time and brain scans showed disrupted satiety signals.

"It is important to note, this change in food liking did not change their caloric intake," said Geha, who first authored a previous study published in PAIN that recent research is building on. "These findings suggest obesity in patients with chronic pain may not be caused by lack of movement but maybe they change how they eat."

Brain scans of the study participants revealed that the nucleus accumbens—a small area of the brain mostly known for its role in decision-making—may offer clues to who is at risk to experience a long-term change in eating behavior. Researchers found the structure of this area of the brain was normal in of patients who initially experienced changes in their eating behavior but whose pain did not become chronic. However, patients whose eating behavior was normal, but whose pain became chronic had smaller nucleus accumbens. Interestingly, the nucleus accumbens predicted pleasure ratings only in chronic back pain patients and in patients who became chronic after an acute bout of back pain suggesting that this region becomes critical in motivated behavior of chronic pain patients. Previous research by Geha, found a smaller nucleus accumbens can indicate if someone is at a greater risk of developing chronic pain.

Additional authors include Yezhe Lin, Ph.D., and Gelsina Stanley of the University of Rochester, Ivan de Araujo, Ph.D., of Icahn School of Medicine at Mount Sinai, and Dana Small, Ph.D., of Yale University.

Researchers restore brain immune system function after prenatal exposure to environmental toxin
by University of Rochester Medical Center

Credit: Pixabay/CC0 Public Domain
New research shows that exposure to the industrial byproduct TCDD in utero could cause the brain's immune system to go array later in life, damaging important brain circuits, and potentially giving rise to neurodevelopmental disorders, such as autism and ADHD. TCDD is primarily released into the environment by vehicle exhaust and burning wood and low levels of the toxin are found in air, soil, and food. The most common way people are exposed is through meat, dairy, and fish.

In the same study, recently published in the journal Brain, Behavior, and Immunity, researchers also found that pharmacological manipulation could restore the function of microglia, important cells in the brain's immune system. "This suggests that defects in microglia function resulting from prenatal exposures can be reversed later in life, indicating a possible additional therapeutic avenue for neurodevelopmental disorders," said Rebecca Lowery, Ph.D., assistant research professor in the Del Monte Institute for Neuroscience at the University of Rochester, and co-first author of the study.

The research, which was conducted in mice, showed that when the brains of males were exposed to TCDD in utero, it caused inflammation which cause microglia to go array when responding to injury. While the microglia themselves appeared healthy, the cells became over activated while responding to injury in a way that could damage important brain circuits. But investigators found that by using the drug Pexidartinib (PLX3397) they could 'shut-off' the hyper-responsive microglia and those were replaced by new microglia that functioned normally.

This work offers new clues to when exposure to TCDD is most dangerous. Past research has found that adults exposed to TCDD did not have inflammation in the brain and there was no impact on microglia function. "Microglia are outside of the brain during pregnancy," said Ania Majewska, Ph.D., lead author on this study. "But after birth they are protected, possibly by the blood brain barrier, this barrier may be what prevents the harmful effects of TCDD from entering the brain." Researchers now want to understand if other environmental exposures impact microglia similarly, and whether these changes lead to long-term alterations in brain circuitry and function.

Exercise post-vaccine bumps up antibodies, new study finds
by Iowa State University

A student walks across ISU's central campus in Ames, IA, Oct. 2015. Credit: Christopher Gannon/Iowa State University
Researchers at Iowa State University found 90 minutes of mild- to moderate-intensity exercise directly after a flu or COVID-19 vaccine may provide an extra immune boost.

In the newly published study, participants who cycled on a stationary bike or took a brisk walk for an hour-and-a-half after getting a jab produced more antibodies in the following four weeks compared to participants who sat or continued with their daily routine post-immunization. The researchers found similar results when they ran an experiment with mice and treadmills.

Antibodies are essentially the body's "search and destroy" line of defense against viruses, bacteria, fungi and parasites. Vaccines help the immune system learn how to identify something foreign and respond by bolstering the body's defenses, including an increase in antibodies.

"Our preliminary results are the first to demonstrate a specific amount of time can enhance the body's antibody response to the Pfizer-BioNtech COVID-19 vaccine and two vaccines for influenza," said Kinesiology Professor Marian Kohut, lead author of the paper published in the journal Brain, Behavior, and Immunity.

The researchers said the study's findings could directly benefit people with a range of fitness levels. Nearly half of the participants in the experiment had a BMI in the overweight or obese category. During 90 minutes of exercise, they focused on maintaining a pace that kept their heart rate around 120–140 beats per minute rather than distance.

In the study, the researchers also tested whether participants could get the same bump in antibodies with just 45-minutes of exercising. They found the shorter workout did not increase the participants' antibody levels. Kohut said the research team may test whether 60 minutes is enough to generate a response in a follow-up study.

Why the boost?

As to why prolonged, mild- to moderate-intensity exercise could improve the body's immune response, Kohut said there may be multiple reasons. Working out increases blood and lymph flow, which helps circulate immune cells. As these cells move around the body, they're more likely to detect something that's foreign.

Data from the mouse experiment also suggested a type of protein (i.e., interferon alpha) produced during exercise helps generate virus-specific antibodies and T-cells.

"But a lot more research is needed to answer the why and how. There are so many changes that take place when we exercise—metabolic, biochemical, neuroendocrine, circulatory. So, there's probably a combination of factors that contribute to the antibody response we found in our study," said Kohut.

The researchers are continuing to track the antibody response in the participants six months post-immunization and have launched another study that focuses on exercise's effects on people who receive booster shots.

Postdoctoral Researcher Tyanez Jones, Graduate Assistant Jessica Alley and Justus Hallam, a graduate student at the time of the study, co-authored the recently published paper with Marian Kohut. Kohut said the research team also received a lot of help from undergraduate students, including students from the ISU Science Bound Scholars Program.

Pfizer booster more than 50% protective against omicron
by Nature Publishing Group

Credit: Unsplash/CC0 Public Domain
A booster dose of the Pfizer–BioNTech vaccine (BNT162b2) against SARS-CoV-2 after an initial two doses of either the CoronaVac inactivated virus vaccine or Pfizer–BioNTech mRNA vaccine is shown to provide protection against the omicron variant, in a pair of papers published in Nature Medicine.

David Hui, Malik Peiris and colleagues investigate differences in antibody responses to infection with wild-type or the omicron variant of SARS-CoV-2 in people who had either recovered from COVID-19 (30 participants; mean age, 48.9 years) or received vaccinations. This included uninfected people one month after their second of two doses of either the Pfizer–BioNTech mRNA vaccine (31 participants; mean age, 51.7 years) or the CoronaVac vaccine (30 participants; mean age, 52.1 years), those who received two doses of CoronaVac and an additional booster dose of CoronaVac (30 participants; mean age, 50.5 years) or three doses of Pfizer–BioNTech (25 participants; mean age, 50.6 years).

The authors found that two doses of either the Pfizer–BioNTech or CoronaVac vaccine provided little neutralizing antibody immunity against omicron infection, even at one month after vaccination. Supplementing two doses of either vaccine with a Pfizer–BioNTech booster vaccination, however, provided acceptable immunity—defined as antibody levels sufficient to elicit greater than 50% protection against SARS-CoV-2—at one month after booster-dose administration. Three doses of the Pfizer–BioNTech vaccine resulted in mean neutralizing antibody titers against omicron a third higher than those elicited by two doses of CoronaVac plus a Pfizer–BioNTech booster. However, three doses of CoronaVac did not elicit sufficient neutralizing antibody responses against omicron.

In a second paper, Akiko Iwasaki and colleagues examine the effectiveness of a three-part vaccine regime, consisting of two doses of CoronaVac followed at least four weeks later by booster vaccination with Pfizer–BioNTech, against the delta and omicron variants of SARS-CoV-2 in 101 participants (70% female; mean age, 40.4 years) in the Dominican Republic.

Participants who received this combination of vaccines had elevated levels of virus-specific antibodies and strong antibody neutralization responses against both the original, ancestral form of SARS-CoV-2 and the delta variant compared to levels prior to the mRNA booster. Although neutralization of omicron was undetectable in those who had received just two doses of CoronaVac, additional booster vaccination with Pfizer–BioNTech resulted in a 1.4-fold increase in antibody neutralization activity against omicron, relative to those who received two doses of Pfizer-BioNTech or Moderna vaccines.

Despite this increase, however, levels of neutralizing antibodies against omicron were still reduced overall by 7.1-fold and 3.6-fold, relative to levels of antibodies against the ancestral virus or delta variant of the virus, respectively. Notably, previous infection with SARS-CoV-2 did not significantly elevate the levels of antibodies against omicron in participants who had received the mixed-vaccine regime.

The authors conclude that these findings further highlight the ability of the omicron variant to evade vaccine- or infection-induced immunity, emphasizing the global importance of booster vaccinations in efforts to combat emerging variants of SARS-CoV-2.

2

Share

Email

Home
Vaccination
DECEMBER 14, 2021

Two doses of BNT162b2 (BioNTech) or Coronavac (Sinovac) vaccines are inadequate against Omicron virus variants
by The University of Hong Kong

Cells are NOT protected from killing by Omicron virus despite addition of serum from individuals vaccinated by Coronavac. Credit: The University of Hong Kong
Researchers at the Department of Microbiology of the University of Hong Kong (HKU) have found that most individuals after given two doses of the vaccine (either BioNtech or Coronavac) do not produce sufficient levels of serum antibodies against the new Omicron virus variant. The public is advised to get a third dose of the vaccine as soon as possible while awaiting for the next generation of more matched vaccine. The results of the study have been accepted for publication in the medical journal Clinical Infectious Diseases. It is available online as a preprint.

Background

The SARS-CoV-2 Omicron variant, first identified in November 2021, is spreading worldwide. This variant is particularly worrisome due to the large number of mutations in the virus that could affect infectivity or vaccine efficacy. To assess the effectiveness of existing COVID-19 vaccines in Hong Kong against this novel variant, researchers at the Department of Microbiology tested the ability of serum samples from fully vaccinated recipients to neutralize this variant. Serum neutralizing antibody titers are currently the only easily reproducible surrogate marker of protection against COVID-19.

Research findings

To test the ability of vaccine recipients' serum antibodies to neutralize the Omicron variant, the team used sera from two groups of vaccine recipients who have received two doses of BNT162b2 (BioNtech) or Coronavac. Each group consists of 25 people.

The study aims to more fully evaluate the health risk of the Omicron variant to the Hong Kong population and the need for a universal third dose.

Cells are protected from killing by Ancestral SARS-CoV-2 after addition of serum from individuals vaccinated by Coronavac. Credit: The University of Hong Kong
Two Omicron variants present in Hong Kong were tested, one from South Africa and the other from Nigeria (with the additional R346K mutation). The ability of serum antibodies to neutralize the Alpha, Beta, and Delta strains was also tested as a control.

Only five out of 25 Biontech vaccine recipients had neutralizing ability against the Omicron variant virus, and the vaccine efficiency was significantly reduced to 20—24%. Compared to the original SARS-CoV-2 strain, the titer of neutralizing antibodies against the Omicron variant has decreased by 36—40 fold.

None of the serum of the 25 Coronavac vaccine recipients contain sufficient antibody to neutralize the Omicron variant at the limit of 1 in 10 dilution.

Implications of the study

1. The Omicron variant virus was able to reduce the effectiveness of two doses of COVID-19 vaccine, particularly against Coronavac. Therefore, COVID-19 vaccine recipients or even those recovered COVID-19 patients may be at a higher risk of breakthrough or reinfection. Our findings suggest that the design of the next generation of COVID-19 vaccine should consider sufficient coverage against this novel viral variant.

2. A third dose of COVID-19 vaccine is needed to enhance the antibody response against the Omicron variant.

3. Whether a third dose of the present Coronavac vaccine will enhance the neutralizing antibody response against the Omicron variant remains to be determined.

Study: COVID-19 variant Omicron significantly reduces virus neutralization ability of BioNTech vaccine
by The University of Hong Kong

Cells infected were infected with each virus alone or virus mixed with blood serum from vaccinated persons. The cells stain blue but when the cells are killed by virus you see a hole (white) in the cell sheet. In the figure you see that the original 2020 SARS-CoV-2 is completely killed by the blood of vaccinated people but the Omicron virus killing is much reduced. Credit: The University of Hong Kong
A recent study jointly conducted by the LKS Faculty of Medicine, The University of Hong Kong (HKUMed) and the Faculty of Medicine, The Chinese University of Hong Kong (CU Medicine) has revealed that Omicron, the latest COVID-19 variant, can significantly reduce the virus neutralization ability of Pfizer BioNTech (BNT162b2) vaccine by 32 folds or more. A similar test of another vaccine used in Hong Kong, CoronaVac, is being conducted and the results will soon be available.

However, vaccines are still likely to be effective in protecting against death and severe disease. The research team thus renewed calls on high-risk groups, such as the elderly and those with immunocompromised conditions or other chronic diseases to get booster doses as soon as possible.

Background

COVID-19 continues to pose major threats to global public health. The emergence of the Omicron virus variant is of great concern because it has more than 35 mutations in its spike protein, which suggests that the newly emerged variant has capacity to escape immunity from past infection or from vaccines. But direct data on escape from vaccine immunity is still awaited.

Testing the blood of people vaccinated with COVID-19 vaccines for ability to kill virus in the test tube (called the virus neutralization test) is one way to establish how well these vaccines protect against symptomatic infection.

Previous studies carried out by Professor David Hui Shu-cheong, Stanley Ho Professor of Respiratory Medicine and Chairman of Department Medicine and Therapeutics, CU Medicine have followed up people vaccinated with the two vaccines used in Hong Kong, Pfizer BioNTech (BNT162b2) and CoronaVac. Results of these studies have been published recently in the journal Respirology.

Research methods and findings

Professor Malik Peiris, Tam Wah-Ching Professor in Medical Science and Professor of Virology at the School of Public Health, HKUMed and Managing Director, Centre for Infection and Immunity (C2i), Hong Kong Science and Technology Park and his team isolated the Omicron variant and carried out the virus neutralization tests to measure virus killing antibody in the serum to the Omicron variant compared with the original SARS-CoV-2 virus.

In the recent initial experiments on Omicron variant, the blood of 10 people vaccinated with two doses of the Pfizer BioNTech (BNT162b2) vaccine was tested against the original SARS-CoV-2 virus from 2020 and the Omicron variant that the School of Public Health, HKUMed isolated from the first Hong Kong case.

The blood tested was collected one month after the second dose of the vaccine, the time when the highest level of virus-killing antibodies in the blood was expected.

"We can see that most individuals had high levels of virus killing (neutralization) activity against the original SARS-CoV-2 but this ability was markedly reduced by 32 folds or more against the Omicron variant," said Professor Peiris. He added that these findings suggest that vaccine-protection against breakthrough infection with Omicron will be much reduced.

The data from CoronaVac vaccinated individuals will also soon be available but because previous studies suggested that virus-killing antibody levels in CoronaVac vaccines were lower than with the BioNTech vaccines, it is very likely that the loss of activity against CoronaVac will also be very large.

Professor Hui has pointed out that antibodies are one (though important) arm of the immune response. The second arm of the immune response is cell mediated immunity and this is less likely to be affected by the Omicron variant. "We may expect that vaccines may still have protective effect against severe disease and death. It is therefore important that all those who are eligible for vaccination get fully vaccinated," he said.

The joint research team will be testing the blood of those who have received a booster-dose of vaccines in the coming week and it is expected that the booster dose will provide increased levels of protection. "It will be important for those who are at higher risk, including older age and those with immunocompromised conditions or other chronic diseases such as diabetes and high blood pressure to take booster doses of vaccine as soon as possible," added Professor Peiris.

1

Share

Email

Home
Vaccination
DECEMBER 9, 2021

Vaccine booster increases protection against COVID, including omicron
by Cyra Patel, Jean Li-Kim-Moy, Robert Booy, The Conversation

Credit: The Conversation
If it's been six months since you got the second COVID vaccine dose, it's time to book in for your booster shot. This will provide additional protection against COVID, including the new Omicron variant.

While the evidence is still emerging, preliminary data suggests a Pfizer booster might give the same protection against Omicron as double-dose vaccination did for the original strain.

Why get a booster?

When you get your first dose of COVID vaccine, your body produces an immune response against a part of the virus called the spike protein. If you're exposed to the SARS-CoV-2 virus, your immune system can recognize and fight the virus quickly.

The immune response to a single dose of COVID vaccine is generally short-lived. So a second dose is needed to have a stronger and longer-lasting response.

Over time, the amount of antibodies in your body decreases—this is referred to as waning immunity.

If the immune response wanes below the level needed for protection against COVID—the "protective threshold"—your immune system may not be able to prevent infection when exposed to the virus.

Vaccine doses given some time after the initial course help boost the level of antibodies above the protective threshold.

How much does immunity wane after 2 doses?

Antibodies decrease over a period of six months or more after the second dose of COVID vaccine.

Vaccine effectiveness against COVID infection decreases, on average, by 18.5 percentage points, six months after completing vaccination.

On a positive note, protection against serious COVID illness, including hospitalization or death, does not seem to be reduced to the same extent, only by about 8 percentage points.

This is likely because other components of the immune response (T cells and immune memory cells) stay in the body for longer than antibodies and prevent serious illness.

Waning protection is more of a concern among elderly and immunocompromised people because they tend to have weaker immune responses to vaccines compared with young, healthy people.

How effective are booster doses?

Antibody levels after a booster dose are higher than those after the initial vaccination course.

Although protection against COVID infection from two doses was slightly lower against Delta than the original strain, a booster dose restores protection to the same level.

In Israel, people who received a booster dose (five or more months after completing vaccination) had infection rates ten times lower than in people who had only received the initial two-dose course.

From a safety perspective, the types and frequency of side effects after the booster dose have been similar to first and second doses.

Credit: The Conversation
Which vaccine should I get as my booster dose?

The two mRNA COVID vaccines available in Australia—Pfizer and Moderna—are so far approved for use as a booster dose.

A recent clinical trial showed several COVID vaccines, including all three currently available in Australia (Pfizer, Moderna and AstraZeneca), and the Novavax and Janssen vaccines, produce strong immune responses after a course of either Pfizer or AstraZeneca vaccines.

Based on what we know so far about immune responses to COVID vaccines, any of these vaccines given as a booster should be effective in reducing your risk of infection, regardless of which vaccine you initially received.

The highest immune responses were seen with mRNA vaccines, but it's too early to tell whether these provide better protection against COVID infections when used as a booster, or how quickly immune responses will wane compared with the other vaccines.

When is the best time to get my booster dose?

Booster doses are timed to boost your antibody levels before they get below the protective threshold. The difficulty with COVID is we don't yet know what the protective immune threshold is.

So the timing also involves other factors such as how much disease is in the community and vaccine availability. Some countries, such as the United Kingdom, have recommended getting a booster dose as soon as three months after the initial course.

The UK has much higher daily cases of COVID, and face the potential for increased Omicron cases in winter, when hospitals are often at capacity due to other common respiratory viruses including influenza. In that context, early boosters are like an insurance policy to prevent an overwhelming winter peak.

However, a shorter interval may mean the boost to the immune response is not as high or long lasting. A longer interval between the first and second dose of COVID vaccine is more effective.

Given the COVID virus is circulating at much lower rates in Australia than other countries and vaccine coverage is generally high, a booster dose six months after the initial course seems reasonable.

With this vaccination schedule, most adults in Australia will be eligible for their booster before winter 2022.

Will the booster protect me against Omicron?

We're still learning how the new Omicron variant, with so many mutations, may change our existing immunity (from past infection or vaccination) to be less effective.

Early laboratory studies show two doses of the Pfizer vaccine provide some immunity against Omicron, but not as much as against previous strains. This means we're likely to see more infections in fully vaccinated people.

However a booster dose appears to improve the immune response to a level similar to that observed against previous strains in fully vaccinated people, and is expected to provide good protection against serious illness.

As more data on the effectiveness of boosters emerges, and if Omicron cases increase rapidly, the recommended timing of booster doses may also change.

While we wait for more data to confirm the vaccines provide good protection against hospitalization and death, we can take some comfort knowing early data indicate this variant may even be less severe than previous ones.

In the future, booster doses may be adapted for emerging variants, much like influenza vaccines are modified each year depending on what new strains are circulating.

The benefits of new vaccine technologies like mRNA is the time required to manufacture new variant vaccines is only about 100 days. So if a vaccine-resistant variant does arise, we might not need to wait too long for an updated vaccine.

4

Share

Email

Home
Vaccination
OCTOBER 8, 2021

What's the difference between a COVID-19 booster shot and a third dose?
by Ileana Varela, Florida International University

Dr. Eneida Roldan administers a COVID-19 vaccine at FIU vaccination site. January 27, 2021. Credit: Florida International University
COVID-19 vaccine choices are getting more complicated. So don't feel bad if you are confused about the different COVID-19 vaccines and who's eligible for what. In addition to the three original vaccines approved by the Food and Drug Administration—Pfizer, Moderna, and Johnson & Johnson—booster shots and third doses are now available. But they are not for everyone. And they are not the same thing.

Dr. Eneida Roldan, FIU Health CEO and clinical director of FIU's vaccine initiative, explained the difference between the new shots.

"A booster shot is for people whose immune response may have weakened over time," Roldan said. "A third dose is for people who may not have had a strong enough immune response from the first two doses." Consult your health care provider about which might be right for you.

Here are some guidelines on eligibility from the Centers for Disease Control and Prevention (CDC).

Booster shot: Pfizer only

The Federal Drug Administration (FDA) has only approved booster shots for the Pfizer vaccine.

Who is eligible for a booster?

Only people initially vaccinated with Pfizer can get the booster. And they must have completed their initial vaccination series at least 6 months ago.
65 years and older
18+ years living in a long-term setting
18+ years with underlying medical conditions including cancer, chronic liver, and kidney disease, weakened immune system. The CDC has a complete list of eligible conditions.
18+ years who live or work in high-risk settings including health care, schools, correctional facilities, homeless shelters.
Third dose- Pfizer and Moderna

Third doses have been approved only for the Pfizer and Moderna vaccines. "You need to get the same vaccine for all three doses. And you need to wait at least 28 days after your second dose," Roldan said.

Who is eligible for a third dose?

People with moderately to severely compromised immune systems. This includes people undergoing cancer treatment, organ or stem cell transplant recipients who take medicine to suppress the immune system, and people with immunodeficiency diseases.

Why get these additional shots?

The CDC says, "an additional dose may prevent serious and possibly life-threatening COVID-19 in people who may not have responded to their initial vaccine series."

There is no approved booster shot or third dose for the Johnson & Johnson vaccine. However, on Oct. 5, the company asked the FDA to authorize boosters for people who received its one-shot vaccine.

Who is eligible for the initial COVID-19 vaccines?

The CDC currently recommends COVID-19 vaccination for all people 12 years and older. Only the Pfizer vaccine is currently approved for children younger than 16, but the pharmaceutical company is hoping to expand to younger children. Pfizer just applied for approval for use in children ages 5 to 11.

Diabetes, metabolic syndrome in mice treated with novel class of compounds
by Julia Evangelou Strait, Washington University School of Medicine

Researchers at Washington University School of Medicine in St. Louis have shown, in mice, that a new class of compounds they developed can improve several aspects of metabolic syndrome. Such conditions often lead to cardiovascular disease, the leading cause of death worldwide. Pictured are two of the compounds (yellow) in the new class—SN-401 (left) and SN-406 (right). Credit: Susheel K. Gunasekar (Sah Lab), Pratik R. Chheda (Kerns Lab)
A study in mice—led by researchers at Washington University School of Medicine in St. Louis—shows that a new class of compounds the scientists developed can improve multiple aspects of metabolic syndrome. An increasingly common group of conditions that often occur together, metabolic syndrome includes type 2 diabetes, high cholesterol, fat buildup in the liver, and excess body fat, especially around the waist. This syndrome often leads to cardiovascular disease, the leading cause of death worldwide.

The study is published in the journal Nature Communications.

Testing one of the compounds referred to as SN-401, the researchers found it treats diabetes by improving the ability of the pancreas to secrete insulin and boosting the ability of other tissues to utilize that insulin to more effectively remove sugar from the bloodstream. In an effort to optimize the treatment, the researchers fine-tuned the compound—creating a class of related compounds—based on their studies of a key protein called SWELL1 (also LRRC8a). The gradual decline of this protein may have a central role in the development of diabetes and other aspects of metabolic syndrome.

"Our goal is to develop better therapies for cardiovascular disease, including diabetes and metabolic syndrome, which are major risk factors for worsening heart and vascular problems," said senior author Rajan Sah, MD, Ph.D., an associate professor of medicine. "We have many treatments for diabetes, but even with those therapies, cardiovascular disease remains a leading cause of death among patients with type 2 diabetes. There is a need for new treatments that work differently from the current standard-of-care therapies."

The protein Sah and his colleagues studied is called SWELL1 because of its role in sensing the size or volume of cells. Their new research reveals that the protein also helps to control insulin secretion from the pancreas and improve insulin sensitivity, including in skeletal muscle and adipose tissue, the body's fat stores.

Surprisingly, the researchers showed that SWELL1 does both of these seemingly independent tasks because the protein has a previously unknown double life. It acts as a signaling molecule, turning on cellular tasks that govern how well cells use insulin and also facilitates the pancreas' secretion of insulin into the bloodstream.

"This protein, SWELL1, has a sort of dual personality," Sah said. "The compound binds to SWELL1 in a manner that stabilizes the protein complex so as to enhance expression and signaling across multiple tissues, including adipose, skeletal muscle, liver, the inner lining of blood vessels, and pancreatic islet cells. This restores both insulin sensitivity across tissue types and insulin secretion in the pancreas."

Sah and his colleagues showed that the SN-401 compound improved multiple aspects of metabolic syndrome in two groups of mice that each developed diabetes from different causes, one because of a genetic predisposition and the other due to a high-fat diet. In addition to improving insulin sensitivity and secretion, treatment with the compound also improved blood sugar levels and reduced fat buildup in the liver. Most of these studies were conducted with an injected form of the compound, but the researchers showed evidence that it also could be effective if taken by mouth.

The researchers further showed that the compound does not have a big impact on blood sugar in healthy mice, which is important for its potential as a future possible therapy. Current medications for diabetes can result in blood sugar levels that are too low. The evidence suggests that this compound does not lower blood sugar in situations when it doesn't need to.

Share

Email

Home
Diseases, Conditions, Syndromes
Home
Vaccination
FEBRUARY 11, 2022

Study: COVID booster effectiveness wanes but remains strong
by Mike Stobbe

Credit: Unsplash/CC0 Public Domain
An early look at the performance of COVID-19 booster shots during the recent omicron wave in the U.S. hinted at a decline in effectiveness, though the shots still offered strong protection against severe illness.

The report, published by the Centers for Disease Control and Prevention on Friday, is considered an early and limited look at the durability of booster protection during the omicron surge that exploded in December and January but has been fading in recent weeks.

"COVID-19 vaccine boosters remain safe and continue to be highly effective against severe disease over time," said Kristen Nordlund, a CDC spokesperson.

The researchers looked at patient visits to hospitals and urgent care centers in 10 states. They estimated how well Pfizer or Moderna booster shots prevented COVID-related visits to emergency departments and urgent care centers, and how well the vaccines prevented hospitalizations.

About 10% of people in the study were boosted. Vaccine effectiveness was higher in people who had received boosters than in people who had received only the original series of shots.

But researchers also found that during the time that the omicron variant has been predominant, vaccine effectiveness against outpatient visits was 87% in people who had gotten a booster two months earlier, but to 66% at four months after. Vaccine effectiveness against hospitalization fell from 91% at two months to 78% by the fourth month.

Those results, however, were based on only a small number of patients—fewer than 200—who had been boosted four months earlier at the time of the omicron wave. And it's unclear if those people had gotten boosters early for medical reasons that may have made them more vulnerable to severe illness.

Effectiveness after a booster was higher last year, when the delta variant was causing most U.S. cases, the study noted.

Health experts expect protection from the vaccines to wane. The U.S. booster campaign was based on evidence that emerged last year that vaccine protection was fading six months after people got their initial vaccinations.

And from the beginning, vaccines have offered less protection against the omicron mutant than earlier versions of the virus. The study couldn't address how protection will hold up against the next variant to come along.

Still, the new study's finding was notable, said Dr. William Schaffner, a Vanderbilt University vaccines expert.

"I'm a little surprised, according to the data, that it's starting to wane already," he said, adding that he would have anticipated higher estimates of vaccine effectiveness at the four-month post-booster mark.

But Schaffner also said he'd like to see more research about the durability of booster protection, adding "let's take this with a grain of salt."

Dr. Michael Saag, an infectious diseases physician at the University of Alabama at Birmingham, said 78% effectiveness against hospitalization "is still pretty effective."

"Anecdotally, I'm seeing very few people die who got boosted," he said, even among those with weakened immune systems. "The vaccines are still working."

1

Share

Email

Home
Vaccination
JANUARY 10, 2022

Expert clears up confusion about COVID-19 boosters
by Jason Howland

Credit: Pixabay/CC0 Public Domain
The Centers for Disease Control and Prevention (CDC) has updated its recommendations for the Pfizer COVID-19 vaccine to expand the use of a single booster dose to 12- to 15-year-olds.

"Everyone at age 12 and up is approved for a booster after they've completed their initial series," says Dr. Melanie Swift, co-chair of Mayo Clinic's COVID-19 Vaccine Allocation and Distribution Work Group.

What constitutes an initial series depends on the COVID-19 vaccine you were given. If it was Johnson & Johnson, it's one shot. If it was an mRNA vaccine, which is Moderna or Pfizer, an initial series is two shots. And if you are immunocompromised and were vaccinated with Moderna or Pfizer, it's three shots.

"To keep it clear, just remember that it's your initial series, however many doses that is, and one booster for now," says Dr. Swift. "At least that is in the United States right now. And that's, with everything COVID, always subject to change."

"The timing of the booster depends upon the brand of your initial series. If you got Johnson & Johnson, it's two months. If you got Pfizer initially, it's five months. If you got Moderna initially, it's six months. Now that might change in the future. But that's the current guidance based upon the available data," she says.

This comes at a time when the omicron variant is spreading rapidly across the nation. The U.S. recently hit a new pandemic high of over 300,000 average new daily cases of COVID-19. And COVID-19 hospitalizations are on the rise, as well.

"We know that one of the things about omicron is that it makes your vaccines less effective. The vaccination protection with two doses of an mRNA vaccine against omicron is down in the 40-something percent range—so not great. But with a booster, that protection goes up over 75%," says Dr. Swift. "We know that in addition to the fact that your immunity just wanes over time, omicron, in particular, is more susceptible to your immune response after the third or booster dose. So we are really encouraging people to get that booster dose."

Preclinical study shows ketogenic diet could enhance pancreatic cancer therapy
by Ludwig Institute for Cancer Research

Credit: Pixabay/CC0 Public Domain
A Ludwig Cancer Research preclinical study has demonstrated that a common weight-loss diet could enhance the efficacy of chemotherapy for pancreatic cancer. Published in the journal Med, the study shows that a ketogenic diet—or high fat, modest protein and very low carbohydrate intake—synergizes with chemotherapy to triple survival time compared to chemotherapy alone in rigorous mouse models of pancreatic ductal adenocarcinoma (PDAC).

The researchers, led by Ludwig Princeton Branch Director Joshua Rabinowitz, also describe findings from an intricate examination of how ketogenic diets affect the metabolism of PDAC tumors, and identify mechanisms that might account for the therapeutic effect. Their findings are now being evaluated in a clinical trial (NCT04631445) testing the benefits of a ketogenic diet in PDAC patients receiving chemotherapy.

"There's been real progress against pancreatic cancer over the past two decades," said Rabinowitz, who is also a Professor in the Department of Chemistry and the Lewis-Sigler Institute for Integrative Genomics at Princeton University. "The problem is that, while a number of patients now see their tumors stabilize or shrink, the benefits of chemotherapy are very short lived. It often extends patients' lives six months to a year, but way too rarely do we see the three-plus years of extension in survival that people would, at a minimum, hope for."

Substantial preclinical evidence suggests that fasting, or diets that resemble fasting in their metabolic effects, could enhance therapy for a variety of cancers. The ketogenic diet mimics fasting by reducing circulating glucose and depressing levels of insulin, a hormone that drives tissues and tumors to consume the sugar. Insulin is an important promoter of cancer growth—especially in pancreatic tumors—while glucose is a critically important fuel for cancer cell proliferation. Rabinowitz's own studies previously revealed that PDAC tumors, despite their aggressive growth, are starved of glucose, which suggested they could be especially vulnerable to additional glucose deprivation.

In the current study, Rabinowitz and his colleagues conducted multiple experiments over many years—with early and ongoing support from Stand Up to Cancer—using mice that were engineered to develop PDAC or implanted with tumors that resembled those seen in patients. The mice were fed either a normal, carbohydrate rich diet or a ketogenic diet and treated with a standard-of-care combination of chemotherapies—nab-paclitaxel (Abraxane), gemcitabine and cisplatin.

They found that the ketogenic diet alone did not affect tumor growth. But it did triple median survival time when combined with chemotherapy. Notably, while the therapeutic benefit did not depend on the immune system, only mice with intact immune systems were among the long-term survivors.

Rabinowitz and his team also conducted studies to explore the effects of the combination therapy on tumor metabolism. "We know that glucose is a major cancer fuel, and insulin is a cancer promoting hormone, and that the ketogenic diet in one stroke decreases both," said Rabinowitz. "We found in this study that the diet decreases levels of glucose more profoundly in the tumor than in healthy tissues and that it dramatically suppresses levels of insulin."

By depriving the body of sugar, the ketogenic diet forces the body to break down fats to generate molecules known as ketone bodies that can be burned by cells to generate energy. Chief among these is 3-hydroxybutyrate.

"One thing we noticed is that 3-hydroxybutyrate acts like a supercharged fuel that dumps electrons into cells, and tumor cells are wired for other reasons to be extra-good at taking up this fuel," said Rabinowitz. "Fortuitously, too much of this super-charged fuel may be toxic to cancer."

This excess of electrons causes the generation of reactive oxygen species (ROS), extremely unstable molecules that are also generated by chemotherapy. ROS kill cancer cells by damaging DNA, membranes and other components of cells. This, the researchers hypothesize, may enhance the antitumor effects of the chemotherapy.

"I think that the most exciting thing here is that we can take chemotherapy regimens that we know to be active, that offer patients the best chance in the clinic right now and, at least in mice, make them work substantially better by pairing them with a ketogenic diet," said Rabinowitz. "We hope that we'll see the same types of benefits in patients."

Could ketogenic diet be helpful with brain cancer?
by American Academy of Neurology

Credit: Unsplash/CC0 Public Domain
A modified ketogenic diet may be worth exploring for people with brain tumors, according to a new study published in the July 7, 2021, online issue of Neurology. The diet is high in fat and low in carbohydrates.

The small study found that the diet was safe and feasible for people with brain tumors called astrocytomas. All of the people had completed radiation treatment and chemotherapy. The diet led to changes in the metabolism in the body and the brain. The study was not designed to determine whether the diet could slow down tumor growth or improve survival.

"There are not a lot of effective treatments for these types of brain tumors, and survival rates are low, so any new advances are very welcome," said study author Roy E. Strowd, MD, MS, MEd, of Wake Forest School of Medicine in Winston-Salem, N.C., and a Fellow of the American Academy of Neurology.

"These cancer cells rely on glucose, or sugar, to divide and grow. Since the ketogenic diet is low in sugar, the body changes what it uses for energy—instead of carbohydrates, it uses what are called ketones. Normal brain cells can survive on ketones, but the theory is that cancer cells cannot use ketones for energy."

The study involved 25 people with astrocytomas. They followed a type of ketogenic diet, the modified Atkins diet with intermittent fasting, for eight weeks. The diet includes foods such as bacon, eggs, heavy cream, butter, leafy green vegetables and fish. Participants met with a dietician at the start of the study and then every two weeks. Five days a week they followed the modified Atkins diet, which combined carbohydrate restriction with high amounts of fats. Two days a week they fasted, eating up to 20% of their recommended daily calorie amount.

The main goal of the study was to see if people were able to follow the diet with no serious side effects. A total of 21 people completed the study, and 48% followed the diet completely, according to their food records. But urine tests showed that 80% of the people reached the level where their body was primarily using fats and protein for fuel, rather than carbohydrates.

The diet was well-tolerated. Two people had serious side effects during the study—one was not related to the diet and one was possibly related.

By the end of the study, changes in the metabolism in the body and the brain were seen. Hemoglobin A1c levels, insulin levels, and fat body mass all decreased. Lean body mass increased. Specialized brain scans that detect changes in brain metabolites showed an increase in concentrations of ketones and metabolic changes in the tumor.

"Of course more studies are needed to determine whether this diet can prevent the growth of brain tumors and help people live longer, but these results show that the diet can be safe for people with brain tumors and successfully produce changes in the metabolism of the body and the brain," Strowd said.

A limitation of the study is that study team members provided a high amount of contact with participants, which may not be feasible in a larger study or in routine clinical care.

New research reveals that a low-calorie ketogenic diet can help testosterone levels in overweight men
by European Society of Endocrinology

Credit: Pixabay/CC0 Public Domain
A very low-calorie ketogenic diet can help testosterone and sex hormone (SHBG) levels in overweight men, according to a study being presented at the 23rd European Congress of Endocrinology (e-ECE 2021), on Monday 24 May 2021. The study found that after following a recommended low-calorie ketogenic diet for four weeks, body weight, fat mass and body mass index (BMI) significantly decreased and a substantial increase of total testosterone and SHBG levels were also found. Testosterone is responsible for sexual and reproductive functions. However, it plays a significant role in calorie utilisation and metabolism as well.

This study was the first of its kind to examine the effect of a very low-calorie ketogenic diet on testosterone and SHBG levels and therefore highlighted the tight relation between insulin action, energy balance, and testicular function. As men who are overweight or obese can also suffer from low levels of testosterone and SHBG levels, the data suggests that further research into a low-calorie ketogenic diet and its effect on male testosterone and SHBG levels may be a promising area for additional research.

The worldwide prevalence of obesity nearly doubled between 1980 and 2008. According to country estimates for 2008, over 50% of men in the WHO European Region were overweight, and roughly 20% were obese. Obesity can lead to diabetes and heart disease, as well as psychological problems.

To tackle this, various lifestyle changes, activities and treatments are widely recommended, and a ketogenic diet is becoming increasingly recognised as one of them. The diet consists of little protein and very little carbohydrates, and when done as very-low calorie a daily intake of less than 800 calories is advised. A very low-calorie ketogenic diet has previously been found to reduce body weight, glycaemia and insulinemia, but its effects on total testosterone and SHBG levels were less clear, until now.

Dr. Angelo Cignarelli and a team of colleagues from the University of Bari in Italy investigated whether this controlled diet would have the same, positive effect that it does on overall bodyweight on total testosterone and SHBG levels. The 17 male subjects in the study underwent a low-calorie ketogenic diet for four weeks, and various tests were carried out before and after one (1) and four (4) weeks.

"We aimed to evaluate the response of total testosterone and sex hormone levels to a very low-calorie ketogenic diet in a cohort of overweight or obese non-diabetic male subjects and what we found was that there is a noticeable relation between a specific, controlled diet and insulin action, energy balance, and testicular function," says Dr. Cignarelli.

This is the first study that has evaluated the early response of androgen levels to the institution of a very low-calorie ketogenic diet, and highlights the relation between insulin action, energy balance, and testicular function. Results from this study now prove that a very low-calorie ketogenic diet can positively effect on total testosterone and SHBG levels. Further analysis will provide information about the effect of this nutritional intervention on additional clinical outcomes related to testosterone such as sexual function, muscle strength and quality of life.

Inflammatory diet linked to testosterone deficiency in men
by Wolters Kluwer Health

Ball-and-stick model of the testosterone molecule, C19H28O2, as found in the crystal structure of testosterone monohydrate. Credit: Ben Mills/Wikipedia
Consuming a diet high in pro-inflammatory foods—including foods that contain refined carbohydrates and sugar as well as polyunsaturated fats—may be associated with increased odds of developing testosterone deficiency among men, suggests a study in The Journal of Urology, Official Journal of the American Urological Association (AUA).

The risk of testosterone deficiency is greatest in men who are obese and consume a refined diet that scores high on the dietary inflammatory index (DII), according to the new research by Qiu Shi, MD, Zhang Chichen, MD, and colleagues of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. "While these findings do not prove causation, they do support previous research suggesting a pro-inflammatory diet can contribute to testosterone deficiency, among other potentially debilitating health issues," Drs. Qiu and Zhang comment.

Does diet influence testosterone levels? New study discovers link

Testosterone is a male sex hormone that plays important roles in reproduction and sexual function. However, 20 to 50 percent of US men have testosterone deficiency—defined as a testosterone level less than 300 ng/dL (nanograms per deciliter). Symptoms of testosterone deficiency may include low libido, decreased energy, poor concentration and depression. Testosterone deficiency is also associated with chronic diseases, including cardiovascular disease and obesity.

Human and animal studies have linked testosterone deficiency with increased levels of inflammation in the body. Men with low testosterone have higher levels of pro-inflammatory cytokines: small proteins released by cells during injury, infection or in response to inflammatory factors in the environment. The DII has emerged as a tool for assessing the inflammatory potential of a person's diet, particularly in relation to other markers of health.

The researchers studied the association between the DII and testosterone deficiency in 4,151 men from the National Health and Nutrition Examination Survey, all of whom completed a 24-hour dietary interview and underwent sex hormone testing. Each participant's DII was calculated based on the dietary history interview.

Calculated DII scores ranged from -5.05 (most anti-inflammatory) to +5.48 (most pro-inflammatory). Average total testosterone level was 410.42 ng/dL in men with the most pro-inflammatory diet versus 422.71 ng/dL in those with the most anti-inflammatory diet. Overall, about 26 percent of the men had testosterone deficiency.

For men with the most pro-inflammatory diet, the odds of testosterone deficiency were about 30 percent higher compared to men with the most anti-inflammatory diet. The associations remained significant after adjustment for other characteristics, including body mass index and smoking.

In a fully adjusted analysis, the risk of testosterone deficiency was greatest in men who were obese and had a higher DII. For this group, the odds of testosterone deficiency were nearly 60 percent higher compared to men with obesity who had a lower DII.

Drs. Qiu, Zhang, and coauthors note some important limitations of their study, including the fact that the DII was calculated based on a limited number of anti-inflammatory and pro-inflammatory food parameters.

"Our results suggest men who eat a pro-inflammatory diet, particularly those who are obese, are more likely to have testosterone deficiency," Drs. Qiu and Zhang comment. "Since men with obesity likely already experience chronic inflammation, physicians should be aware of contributing factors, like diet, that could likely worsen this inflammation and contribute to the risk of other health conditions, such as diabetes and heart disease."

Drs. Qiu and Zhang and colleagues call for further studies to verify the causal relationship between DII and testosterone deficiency. They also suggest that consuming a more anti-inflammatory diet "could be a feasible method to reduce the accumulated inflammatory burden, [potentially] leading to an increased testosterone level."

4

Share

Email

Home
Health
JANUARY 10, 2020

Low-fat diet linked to lower testosterone levels in men
by Wolters Kluwer Health

Credit: CC0 Public Domain
For the many men diagnosed with testosterone deficiency, losing weight can help increase testosterone levels. But certain diets—specifically a low-fat diet—may be associated with a small but significant reduction in testosterone, suggests a study in The Journal of Urology, Official Journal of the American Urological Association (AUA).

"We found that men who adhered to a fat restrictive diet had lower serum testosterone than men on a nonrestrictive diet," according to the report by Jake Fantus, MD, of the Section of Urology, Department of Surgery, University of Chicago Medicine and colleagues from the Department of Urology, Northwestern University Feinberg School of Medicine, and the Department of Surgery, NorthShore University Health System. "However," the researchers add, "the clinical significance of small differences in serum T across diets is unclear."

Best Diet for Low Testosterone? No Single Right Answer Yet

Dr. Fantus and colleagues analyzed data on more than 3,100 men from a nationwide health study (the National Health and Nutrition Examination Survey, or NHANES). All participants had available data on diet and serum testosterone level.

Based on two-day diet history, 14.6 percent of men met criteria for a low-fat diet, as defined by the American Heart Association (AHA). Another 24.4 percent of men followed a Mediterranean diet high in fruits, vegetables, and whole grains but low in animal protein and dairy products. Only a few men met criteria for the AHA low-carbohydrate diet, so this group was excluded from the analysis.

The average serum testosterone level was 435.5 ng/dL (nanograms per deciliter). Serum testosterone was lower in men on the two restrictive diets: average 411 ng/dL for those on a low-fat diet and 413 ng/dL for those on the Mediterranean diet.

The associations were adjusted for other factors that can affect testosterone, including age, body mass index, physical activity, and medical conditions. After adjustment, the low-fat diet was significantly associated with reduced serum testosterone, although the Mediterranean diet was not.

Overall, 26.8 percent of men had testosterone levels less than 300 ng/dL. Despite the difference in average testosterone levels, the proportion of men with low testosterone was similar across all diet groups.

Low testosterone is highly prevalent in the United States, as approximately 500,000 men are diagnosed with testosterone deficiency each year. Testosterone deficiency can lead to problems, including decreased energy and libido, along with physiological alterations, including increased body fat and reduced bone mineral density.

In addition to medications, treatment for low testosterone often includes lifestyle modifications, such as exercise and weight loss. But the effects of diet on testosterone levels have been unclear. Because testosterone is a steroid hormone derived from cholesterol, changes in fat intake could alter testosterone levels. This new analysis of how diet affects serum testosterone provides evidence that a low-fat diet is associated with lower testosterone levels, compared to an unrestricted diet.

So what diet is best for men with testosterone deficiency? The answer remains unknown, according to the authors. In overweight or obese men, the health benefits of a low-fat diet likely far exceed the small reduction in serum testosterone. In contrast, for men who are not overweight, avoiding a low-fat diet "may be a reasonable component" of a multifaceted approach to increasing serum testosterone.

Dr. Fantus and coauthors note that further studies will be needed to corroborate their findings, and to clarify the mechanism by which restrictive diets reduce testosterone. But due to the difficulties of large-scale dietary studies, definitive trials are unlikely to be performed. "Therefore, our data represent a valuable approach towards answering this important question," the authors conclude.

Fewer fats over the festive season may be the perfect formula for men's fertility
by University of South Australia

Credit: Shutterstock
A diet low in fat and high in egg whites could be the key to boosting male fertility according to a new pilot study.

The research, by Dr. Karma Pearce from the University of South Australia in collaboration with fertility specialist Prof Kelton Tremellen, Repromed, and Flinders University, presents a direct link between diet and testosterone—showing that what men eat could affect their fundamental male sex hormone.

The study is the first to identify that a diet high in any type of fat—including healthy mono-saturated fats such as olive oil—negatively impacts testosterone production over as little as five hours, yet one supplemented with egg whites, and to a lesser extent whey protein, can positively affect serum testosterone.

Globally, infertility affects 15 percent of couples, with the World Health Organization estimating that up to 25 percent of couples in developing countries are affected. While the causes are many and varied, 20-30 percent of the problems are attributed to male factors alone.

Lead researcher, Dr. Karma Pearce, says the preliminary findings present controversial insights over the shorter five-hour term about the link between testosterone and "healthy" monounsaturated fat, which is popularly considered to be a component of a healthy diet, including the Mediterranean dietary pattern.

"There's an assumption that 'good' fats and 'bad' fats perform as they're described—but what's surprising, is that it wasn't the type of fat that mattered at all, as an equal amount of the good and bad fats significantly supressed testosterone production," Dr. Pearce says.

While the researchers acknowledge they have tested individual nutrients and the effects may be different in the context of whole food dietary patterns, their earlier work has shown that "Western diets' typified by fast food dietary pattern produced a 25 percent decrease in serum testosterone within an hour of eating, with levels remaining suppressed below fasting baseline for up to four hours.

"In this study we also found that consuming albumen—the protein in egg whites—increased testosterone levels, and did so by four-fold relative to fasting, while albumin, combined with the bad saturated fat somewhat ameliorated the effect of the bad fats on testosterone levels, providing another diet-based influencer of testosterone levels."

The study tested eight diet protocols (meals comprising polyunsaturated fat; monounsaturated fat; refined carbohydrate (orange juice); whey; egg white; and mixed meals of polyunsaturated fat and refined carbohydrate; polyunsaturated fat and egg white; refined carbohydrate (orange juice) and egg white) with four blood tests/hormone analyses taken before eating and at every hour afterwards for five hours.

Dr. Pearce says the study is one step in a series of work needed to support and enhance fertility.

While the study only analyses the impact of various dietary macronutrients on testosterone production, not sperm quality, the researchers believe the study results suggest at least the potential for diet to negatively impact on sperm production and fertility. The findings are extremely promising for couples trying to start a family.

"It's important to note that it's still early days and more research needs to be done, particularly at looking at the effect of these nutrients in the context of whole food dietary patterns over the longer-term," Dr. Pearce says. "Over the Christmas period, for infertile men, and men with lower than normal testosterone levels, lowering the overall fat content and possibly increasing whey or adding egg whites may lead to improvements in testosterone levels over the shorter term."

The next step in their research is to evaluate the longer-term effect of these nutrients on testosterone levels in the context of whole food dietary patterns.

"The Effect of Macronutrients on Reproductive Hormones in Overweight and Obese Men: A Pilot Study" is published in the journal Nutrients.

Fast food leads to slow testosterone
by Flinders University

Credit: CC0 Public Domain
Obese men hoping to sire children—beware. Obesity is known to be associated with impaired testicular function, potentially resulting in androgen deficiency and sub-fertility. Now it is clear that fast food meals consumed by obese or overweight men have an immediate negative impact on testicular performance and testosterone production.

While many facts are involved in the underlying cause of obesity-related male hypogonadism, Flinders University and UniSA researchers have found that a high fat intake from fast food meals has a decisive negative effect on a man's serum testosterone levels.

Their investigation into the impact of dietary fat on testicular endocrine function showed some alarming results. They found that the ingestion of a high-fat Fast Food mixed meal, which is a common practice for obese men, produced a 25% fall in serum testosterone within an hour of eating, with levels remaining suppressed below fasting baseline for up to 4 hours.

These results—which only investigated the impact on overweight and obese men, and therefore may not apply to lean men—suggest that the passage of fat through the intestinal tract elicits a response that indirectly elicits a post-prandial fall in testosterone.

"The observed falls in serum testosterone (25% decline from baseline, 2–3 nmol in absolute terms) are likely to be clinically significant for the obese or older man with low baseline levels of testosterone," says Flinders University's Professor Kelton Tremellen, Gynaecologist and Strategic Professor of Reproductive Medicine, who undertook the research with Dr. Karma Pearce from UniSA.

"These men are likely to be placed into a continuous hypogonadal state during waking hours if they frequently consume meals and snacks high in fat. This will clearly have an adverse impact on both their mental and physical wellbeing, plus possibly their fertility potential.

"Our results suggest that these men should minimize their fat intake and avoid inter‐meal snacking in order to optimize testicular function."

The paper—"Mechanistic insights into the aetiology of post-prandial decline in testosterone in reproductive-aged men," by Kelton Tremellen, Amy Hill and Karma Pearce, has been published in Andrologia journal, September 2019