October Newsletter
In This Issue
Prevent Insulin Resistance
Fishing for Heart Disease
COVID Vaccine?
A Better Model of Medical Care
Old-fashioned medicine with 21st Century convenience and technology
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Welcome to the October newsletter. The goal of this newsletter is to provide information and analysis of timely topics from recent articles published in the medical literature. I hope you find this information useful and helpful in your health journey.   
Last month we discussed the optimum diet to reduce our risk of chronic disease and mortality, improve our insulin sensitivity, and gets us the nutrients we need without weight gain; the pesco-Mediterranean diet (possibly incorporating some intermittent fasting). In this month's first article we are going to focus on insulin resistance. The development of insulin resistance is the first step toward diabetes and chronic disease so improving our insulin sensitivity may be the most important thing we can do for our health. This study focuses on children, but I think the lessons from this research are applicable to us all. 

We have all heard of omega-3 fatty acids. We probably know they are good for us. Why are they important? Research is showing that omega-3's are beneficial for many issues but this article focuses on heart disease and heart attacks. Can they reduce our risk? Where can we get omega-3's in our diet? How much do we need to make a difference? What if I don't like fish? Read on for all the answers.  

COVID-19 (Sars-CoV-2) is dominating our news, especially here in Wisconsin where we are experiencing our highest number of cases and hospitalizations. We hear news about a potential COVID vaccine, but we are not anywhere close to having one available. It's flu shot season and besides protecting us from influenza there may be another reason to get a flu shot. Check out the third article for more information. 
Information regarding COVID-19 is constantly changing. Wisconsin is currently a "hot spot" for the virus. If you are feeling sick or concerned about symptoms, please call me first. We can discuss your symptoms and decide the best course of action for you, including testing. I have saliva based COVID-19 PCR tests available in my office with 24+ hour turnaround. Serum antibody tests can be performed as well with 24-hour turnaround. Please continue to wash your hands frequently, avoid touching your face, and avoid going out if you are sick.   
Prevent Insulin Resistance
Physical activity and dietary intervention prevent increased insulin resistance
The development of insulin resistance is the first step toward diabetes and chronic disease. Research has shown that our children are now born insulin resistant and this continues to increase throughout childhood. There is a rapid increase in insulin resistance that occurs during the progression to puberty. This study was designed to see if increased physical activity and dietary intervention would have any effect on the development of insulin resistance in normal weight children. The children were divided into two groups and followed for two years. They used nutritional analysis, blood work to follow blood glucose and insulin levels along with DEXA scans to determine body composition (the most accurate means of assessment). The results showed that combined physical activity and nutritional intervention attenuated the increase in insulin resistance typically seen. There was no change in body composition so the loss of body fat was not the cause. Changes in physical activity (and less sedentary time) result in prevention of the progression of insulin resistance. Prevention of type 2 diabetes can start in childhood.  

  • Aims/hypothesis: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children.
  • Methods: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6-9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects.
  • Results: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient β for intervention effect −0.33 [95% CI -0.62, -0.04], p = 0.026) and HOMA-IR (β for intervention effect −0.084 [95% CI -0.156, -0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR.
  • Conclusions/interpretation: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition.
Most of the focus of prevention of type 2 diabetes focuses on overweight people, including children. Obesity has increased by 70% in adults aged 18-29 years, and type 2 diabetes has increased in parallel by 70% in adults aged 30-39 years over the last decade, making young adults the fasting growing adult group for both obesity and type 2 diabetes. The early development of insulin resistance means increased risk for comorbidities such as cardiovascular disease, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), osteoarthritis, obstructive sleep-apnea (OSA), and some forms of cancer This study is very interesting because it focuses on presumed healthy normal weight children. There is normally increased development of insulin resistance at the time of puberty. This study took prepubertal children and intervened to see if the development of insulin resistance could be attenuated. They found that increased physical activity, reduced sedentary activity, and nutritional intervention had a significant effect on the development of insulin resistance. This was achieved with no change in body composition which is good since the children were normal body composition at the onset of the study. 

What can we take away from this study as adults? Increased physical activity, less sedentary time, and nutritional interventions can improve insulin resistance in kids, so it seems very likely that this works in adults as well. Even if we are not losing weight we can improve our insulin resistance which will then lower our risk of development of type 2 diabetes, metabolic syndrome (increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels), liver disease, kidney disease, sleep apnea, arthritis, and some forms of cancer. Sounds like a winner to me! You may want to review last month's newsletter for a great nutrition plan to achieve this. 
Fishing for Heart Disease
Omega-3 supplementation linked to a reduction in heart attacks and coronary heart disease 
fish oil

Supplementation with omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with a reduced risk for myocardial infarction (MI) and coronary heart disease (CHD) events according to a meta-analysis published in Mayo Clinic Proceedings. The study looked at 40 studies with 135,267 participants to determine the effects of EPA/DHA supplementation on cardiovascular disease. Supplementation was associated with a reduced risk of heart attack (fatal and non-fatal), coronary heart disease, and coronary heart disease mortality. 

  • Objectives: To quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention and the effect of dosage.
  • Methods: This study is designed as a random effects meta-analysis and meta-regression of randomized control trials with EPA/DHA supplementation. This is an update and expanded analysis of a previously published meta-analysis which covers all randomized control trials with EPA/DHA interventions and cardiovascular outcomes published before August 2019. The outcomes included are myocardial infarction (MI), coronary heart disease (CHD) events, CVD events (a composite of MI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduled cardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.
  • Results: A total of 40 studies with a combined 135,267 participants were included. Supplementation was associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certainty number needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certainty NNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT = 128; and CHD mortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT = 431, but not CVD events (RR, 0.95; 95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI.
  • Conclusion: Cardiovascular disease remains the leading cause of death worldwide. Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.

Omega-3 fatty acids are found in foods such as fish and flaxseed and in dietary supplements, such as fish oil. It is difficult for our bodies to make omega-3 fatty acids so consuming EPA and DHA directly from foods and/or dietary supplements is the only practical way to increase levels of these fatty acids in the body.

Studies have shown omega-3 fatty acids may help to:
  • Lower blood pressure.
  • Reduce triglycerides.
  • Slow the development of plaque in the arteries.
  • Reduce the chance of abnormal heart rhythm.
  • Reduce the likelihood of heart attack and stroke.
  • Lessen the chance of sudden cardiac death in people with heart disease.
This study adds to the growing medical literature showing the benefits of omega-3's in our diet. 

What is the best way to get omega 3's in our diet and how much should we get? The Dietary Guidelines for Americans state that:
  • Strong evidence from mostly prospective cohort studies but also randomized controlled trials have shown that eating patterns that include seafood are associated with reduced risk of CVD, and moderate evidence indicates that these eating patterns are associated with reduced risk of obesity.
  • For the general population, consumption of about 8 ounces per week of a variety of seafood, which provide an average consumption of 250 mg per day of EPA and DHA, is associated with reduced cardiac deaths among individuals with and without preexisting CVD."
  • The recommendation to consume 8 or more ounces per week (less for young children) of seafood is for the total package of nutrients that seafood provides, including its EPA and DHA content. Some seafood choices with higher amounts of EPA and DHA should be included.
  • Seafood varieties commonly consumed in the United States that are higher in EPA and DHA and lower in methyl mercury include salmon, anchovies, herring, shad, sardines, Pacific oysters, trout, and Atlantic and Pacific mackerel (not king mackerel, which is high in methyl mercury).
  • For more information about building a healthy diet, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture's MyPlate.
Including the seafood listed above fits well with the pesco-Mediterranean diet we discussed last month. 

For many of us, eating enough seafood may be difficult. For people with known coronary heart disease, my recommendation would be to have more than 250 mg/day. This meta-analysis found that each 1gram/day is associated with a reduction of 5.8% in the risk of cardiovascular disease events and 9% reduction in heart attack risk. More is better and most of us can't eat enough fish to get to these levels so it makes sense to supplement omega 3's. The easiest way to do this is fish oil. For general prevention, I would recommend 1 gram daily which should get you to the 250 mg of DHA/EPA daily level. If you have known heart disease (coronary artery calcifications) or have had a stent placed then I would recommend a higher dose. I usually shoot for 3 grams of DHA/EPA daily. If you look at your bottle, it will tell you how much of each is in a capsule. Most fish oils will require 4 or more capsules daily. It is very important to get high-quality fish oil and never take fish oil that smells rancid or is expired. To avoid "fish burps" store your fish oil in the refrigerator or freezer and take with food. 
COVID Vaccine?
Flu vaccine may provide some protection against COVID-19
Flu shot
This study from the Netherlands and Germany found that health care workers who had gotten a flu vaccination the previous year had a lower risk of getting COVID-19. In the lab, they also studied the response of cells treated with the flu vaccine when exposed to COVID-19 and found that the treated cells had a trained immune response which showed an improvement in the cytokine response which leads to severe complications in people with COVID-19. The idea is that some vaccines can not only train the part of the immune system to recognize a specific germ but also temporarily boost the effectiveness of our innate immune system which is our first line of defense against unfamiliar pathogens. This is sometimes referred to as "trained immunity". 
  • Every year, influenza causes 290.000 to 650.000 deaths worldwide and vaccination is encouraged to prevent infection in high-risk individuals. Interestingly, cross-protective effects of vaccination against heterologous infections have been reported, and long-term boosting of innate immunity (also termed trained immunity) has been proposed as the underlying mechanism. Several epidemiological studies also suggested cross-protection between influenza vaccination and COVID-19 during the current pandemic. However, the mechanism behind such an effect is unknown. Using an established in-vitro model of trained immunity, we demonstrate that the quadrivalent inactivated influenza vaccine used in the Netherlands in the 2019-2020 influenza season can induce a trained immunity response, including an improvement of cytokine responses after stimulation of human immune cells with SARS-CoV-2. In addition, we found that SARS-CoV-2 infection was less common among Dutch hospital employees who had received influenza vaccination during the 2019/2020 winter season (RR = 0,61 (95% CI, 0.4585 - 0.8195, P = 0.001). In conclusion, a quadrivalent inactivated influenza vaccine can induce trained immunity responses against SARS-CoV-2, which may result in relative protection against COVID-19. These data, coupled with similar recent independent reports, argue for a beneficial effect of influenza vaccination against influenza as well as COVID-19, and suggests its effective deployment in the 2020-2021 influenza season to protect against both infections.
Should we get flu shots this year? I suspect that this will be a "mild" year for influenza infections based on the social distancing, mask-wearing, and hand washing we are all doing. The incidence of influenza in the Southern hemisphere has been very low this year as compared to a normal year. But there may be another reason to get a flu shot. It's called trained immunity. This study and others have suggested that the flu shot boosts our trained immunity, the ability of our immune system to fight off unfamiliar pathogens. These studies show that the influenza vaccine can likely induce trained immunity responses against COVID-19, resulting in relative protection. It won't prevent all cases of COVID or influenza, but will provide some protection and may result in a milder case. With the surge of cases here in Wisconsin, it is a safe and easy way to potentially protect yourself by "training" your natural immune system. 

Thank you for taking the time to read through this newsletter. I hope you have found this information useful as we work together to optimize your health. Feel free to pass this on to anyone you think would benefit from this information. 

You can find previous newsletters archived on my website here


As always, if you have questions about anything in this newsletter or have topics you would like me to address, please feel free to contact me by email, phone, or just stop by! 

To Your Good Health,
Mark Niedfeldt, M.D.