August Newsletter
In This Issue
Exercise is Medicine
Supplement Increases Dementia Risk
Ice Bucket Challenge Follow Up
A New Model of Medical Care
Dr. Niedfeldt
Old-fashioned medicine with 21st Century convenience and technology
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I hope this newsletter finds you and your family well.

It's hard to believe it is the end of August. I was driving today and noticed some trees starting to change. I guess fall isn't far behind. The good news is we should have some wonderful weather left to enjoy here in Wisconsin.  


I really like the saying 'Exercise is Medicine'. This is the name of a global health initiative through the American College of Sports Medicine. This month I highlight a couple studies showing how true this is. The first study shows us that a sedentary lifestyle is about as detrimental as smoking. The second demonstrates that people with high levels of physical activity has much lower rates of chronic disease. Prevention is always better than treatment. Exercise is prevention.  

Calcium supplements are routinely recommended for women from the teen years through old age to aid with bone health. But is there risk to your calcium supplement? The second section looks at a possible link of calcium supplements and dementia.   


The 'Ice Bucket Challenge' swept the country two years ago and raised over $100 million for ALS research. So what happened to that money. The great news is that funding raised from the challenge has led to an important discovery.  


Click on the links the the left to check out our web site...

Exercise Is Medicine
Higher levels of fitness reduce multiple diseases and death                  workout-partners-bikes.jpg
A quick quiz. What is the most important thing for longer life? 
A. Not smoking
B. Cholesterol level
C. Blood pressure
D. Fitness level 

While all are important (although cholesterol is a bit debatable) the answer is not smoking. However, the first study, from the  European Journal of Preventive Cardiology, found that the second most important thing was fitness level. 

The second study for this section looked at the relationship between physical activity and risk of major diseases including several cancers, heart disease, and strokes. This study, from BMJ, analyzed 174 scientific articles and found that people with higher activity levels had significantly reduced risk of these major diseases.  
Summary of findings:
  • Background: Low aerobic capacity has been associated with increased mortality in short-term studies. The aim of this study was to evaluate the predictive power of aerobic capacity for mortality in middle-aged men during 45-years of follow-up.  
  • Design: The study design was a population-based prospective cohort study.
  • Methods: A representative sample from Gothenburg of men born in 1913 was followed from 50-99 years of age, with periodic medical examinations and data from the National Hospital Discharge and Cause of Death registers. At 54 years of age, 792 men performed an ergometer exercise test, with 656 (83%) performing the maximum exercise test.
  • Results: In Cox regression analysis, low predicted peak oxygen uptake (), smoking, high serum cholesterol and high mean arterial blood pressure at rest were significantly associated with mortality. In multivariable analysis, an association was found between predicted tertiles and mortality, independent of established risk factors. Hazard ratios were 0.79 (95% confidence interval (CI) 0.71-0.89; p < 0.0001) for predicted , 1.01 (1.002-1.02; p < 0.01) for mean arterial blood pressure, 1.13 (1.04-1.22; p < 0.005) for cholesterol, and 1.58 (1.34-1.85; p < 0.0001) for smoking. The variable impact (Wald's χ2) of predicted tertiles (15.3) on mortality was secondary only to smoking (31.4). The risk associated with low predicted was evident throughout four decades of follow-up.
  • Conclusion In this representative population sample of middle-aged men, low aerobic capacity was associated with increased mortality rates, independent of traditional risk factors, including smoking, blood pressure and serum cholesterol, during more than 40 years of follow-up.                      

Summary of findings:
  • Objective: To quantify the dose-response associations between total physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events.
  • Design: Systematic review and Bayesian dose-response meta-analysis.
  • Data sources: PubMed and Embase from 1980 to 27 February 2016, and references from relevant systematic reviews. Data from the Study on Global AGEing and Adult Health conducted in China, Ghana, India, Mexico, Russia, and South Africa from 2007 to 2010 and the US National Health and Nutrition Examination Surveys from 1999 to 2011 were used to map domain specific physical activity (reported in included studies) to total activity.
  • Eligibility criteria for selecting studies: Prospective cohort studies examining the associations between physical activity (any domain) and at least one of the five diseases studied.
  • Results: 174 articles were identified: 35 for breast cancer, 19 for colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic stroke (some articles included multiple outcomes). Although higher levels of total physical activity were significantly associated with lower risk for all outcomes, major gains occurred at lower levels of activity (up to 3000-4000 metabolic equivalent (MET) minutes/week). For example, individuals with a total activity level of 600 MET minutes/week (the minimum recommended level) had a 2% lower risk of diabetes compared with those reporting no physical activity. An increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%. The same amount of increase yielded much smaller returns at higher levels of activity: an increase of total activity from 9000 to 12000 MET minutes/week reduced the risk of diabetes by only 0.6%. Compared with insufficiently active individuals (total activity <600 MET minutes/week), the risk reduction for those in the highly active category (≥8000 MET minutes/week) was 14% (relative risk 0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789, 0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25% (0.754, 0.704 to 0.809) for ischemic heart disease; and 26% (0.736, 0.659 to 0.811) for ischemic stroke.
  • Conclusions: People who achieve total physical activity levels several times higher than the current recommended minimum level have a significant reduction in the risk of the five diseases studied. More studies with detailed quantification of total physical activity will help to find more precise relative risk estimates for different levels of activity.
Physical Activity and Risk of Breast Cancer, Colon Cancer, Diabetes, Ischemic Heart Disease, and Ischemic Stroke Events: Systematic Review and Dose-Response Meta-Analysis for the Global Burden of Disease Study 2013 BMJ 2016 Aug 01;354(xx)i3857, 

These two studies add to the knowledge that exercise is truly medicine. In fact, it is better than medicine. It prevents disease before medications or treatments are needed! As we age, there are generally 4 health-related concerns that we all have; cancer, heart disease, stroke, and dementia. The first study showed that each increase in VO2max (a measure of aerobic fitness) had a 21% lower risk of death over 45 years of follow up. This is independent of blood pressure and cholesterol levels. 

After an extensive review of the medical literature, the second study showed that people with physical activity levels that here higher had a 14% reduction in breast cancer, 21% reduced risk of colon cancer, 28% reduced risk of diabetes, 25% reduced risk of heart disease and 26% reduced risk of stroke. To achieve these levels of risk reduction, higher than minimum physical activity was required. These findings were for people who performed very high amounts of vigorous levels of physical activity. However, these studies again show that with exercise, it appears more is better and some exercise is definitely better than none. 
Supplement Increases Dementia Risk
Calcium supplements linked to increased risk of dementia in women

Calcium supplements, vitamin D and weight-bearing exercise are standard recommendations for aging women to prevent and treat osteopenia and osteoporosis (weakening of the bones). However, a new study in the journal Neurology, shows that calcium supplements may actually increase risk of dementia. 
Summary of findings      
  • Objective: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up.  
  • Methods: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70-92 years. At baseline in 2000-2001, and at follow-up in 2005-2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria.
  • Results: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01-4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54-12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36-33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28-6.96, p = 0.011), but not in groups without these conditions.
  • Conclusions: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed.                      
Th is study shows that there potentially is an increased risk of dementia from taking calcium supplements. This study followed 700 women between the ages of 70-92 for 5 years. 
Ninety -eight of the women were taking calcium supplements. During the study 54 women had strokes and 59 women developed dementia. The dementia risk was seven times higher for the women who had a stroke and took calcium  supplements
 and three times higher in women who took calcium but didn't have a stroke. Although this was an observational study and can't prove causality, it is rather compelling. Higher levels of calcium in the blood may lead to earlier death of neurons which may account for the findings. At this point, it is important to consider the risks and benefits of calcium supplementation. I have always felt that vitamin D was the most important supplement for bone health and people should get their calcium intake from foods which would not cause the findings seen and still improve the strength of bones. Weight-
bearing exercise is also a key for bone health. 
Ice Bucket Challenge Follow Up
Money raised by challenge led to significant ALS gene discovery
Some of you may have taken part in the hugely popular "Ice Bucket Challenge"  to benefit the ALS Association a couple years ago. This challenge, which involved pouring a bucket of ice water over your head and then challenging others to do the same or give a donation to for ALS swept the country. Now we find that the money donated from the challenge funded a study that has discovered an important new amyotrophic lateral sclerosis (ALS) gene. The study, which involved more than 80 researchers in 11 countries, was published online July 25 in Nature Genetics. The ALS Association used Ice Bucket Challenge donations to fund Project MinE, an international effort to sequence the genomes of at least 15,000 individuals with ALS.

The NEK1 gene was discovered through a search for ALS risk genes in 1,022 families with a history of ALS. Further gene testing, of more than 13,000 patients with ALS who did not have a family history of the disease, also revealed over-representation of variants in the NEK1 gene.

"Global collaboration among scientists, which was really made possible by ALS Ice Bucket Challenge donations, led to this important discovery," study co-leader John Landers, Ph.D., from the University of Massachusetts Medical School in Worcester, said in an ALS Association new release. "It is a prime example of the success that can come from the combined efforts of so many people, all dedicated to finding the causes of ALS. This kind of collaborative study is, more and more, where the field is headed."
Summary of findings:   
  • To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
I remember watching people do the ice bucket challenge and wondering what would come of the money that was raised. It is truly heartening to see that this fun stunt raised a significant amount of money that was then used to make a hopefully ground breaking discovery. This should help all the participants feel good about their participation.

My favorite video was Patrick Stewart's ice bucket challenge.  
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. 


Regular readers of my newsletter know how much I value physical activity for disease prevention. These studies show that not only does it help you live longer, it significantly reduces risk of the major chronic disease as well as cancer. Get moving!



Calcium supplements are routinely recommended for bone health. We certainly need to address risks and benefits, but I would encourage dietary calcium intake over supplements, vitamin D supplement and weight bearing exercise.  


It's good to know that proceeds from the 'Ice Bucket Challenge' have been put to good use. Hopefully, this will help lead to a cure for this terrible disease.  


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.