 The foundation of this practice is lifestyle medicine. Lifestyle medicine uses lifestyle factors to promote healthy aging. The 4 drivers of healthspan and longevity are:
Below, I will discuss each of these fundamentals: Activity is the single most important factor of healthspan. We have seen that even 10 minutes a day of exercise could add years to a person's life (Church, 2007). And perhaps less newsworthy, but certainly interesting, was a study published in 2014 that showed runners were far less likely to die of heart disease regardless of BMI or smoking status (Artero, 2014). In an article published in the Journal of the American Medical Association, the Cleveland Clinic analyzed 23 years of patient data and 122,007 patients. They evaluated the association of all-cause mortality (death for any reason) and cardiorespiratory fitness. They also evaluated age, gender, race/ ethnicity, and co-morbidities such as diabetes, hypertension, smoking and coronary artery disease (CAD). The findings were remarkable. Their findings on typical risk factors were consistent with what we often see. Having diabetes, CAD, smoking, or hypertension conferred approximately a 1.2-1.4X mortality risk or an approximately 20-40% increase risk of death from any cause, but here is the remarkable aspect, being out of shape or having low fitness conferred a 5.0X mortality risk that is a 400% increase risk of death from any cause over any time period. In other words being out of shape was 3 to 4 times worse than smoking, having diabetes or having CAD. (Mandsager, 2018) (For more information see my post on VO2 max) Sleep Sleep has become the new currency. Studies have shown that adequate sleep lowers the risk of some cancers (Thompson, 2011; Irwin,1994; Hakim, 2014), the risk of diabetes (Knutson,2007; Sheen,1996) and helps maintain heart health. One study showed that 6 or less hours of sleep led to a 200-300% increased risk of coronary artery calcification (King, 2008). Proceedings of the National Academy of Sciences (PNAS) published an article that found limiting sleep to less than 6 hours for 1 week changed the activity of 711 genes or about 3% of the total genome (Möller-Levet, 2019). It found that the sleep reduction down-regulated genes that were associated with healthy immune functioning and up-regulated genes associated with chronic inflammation and tumor production. (For more information see my post on sleep.) Nutrition: Nutrition is a loaded term. It has a different meaning to different groups of people. From a healthspan perspective, there are many ways to eat well. I believe the most important thing we can do is to keep sugars low. According to the 2010 Dietary Guidelines advisory committee our top sources of calories for North Amercians come from:
When our top sources of calories are grain based desserts, processed foods and sodas, we are setting ourselves up for long term health consequences. High sugar foods and processed foods containing sugars are known risk factors for diabetes, obesity, metabolic syndrome, cancers, autoimmune diseases and chronic inflammation (Ma, 2022). Once we have minimized sugars we can begin to look at timing and quantity of food, fiber and protein intake based on genetics, labs, activity and goals. (For more information please see this post.) Emotional health and mental wellbeing: Maintaining emotional health takes many forms. There is no one size fits all. For some meditation may be an important factor for others, community gives them a sense of wellbeing. Meditation practices as short as 3-4 minutes have been shown to increase parasympathetic tone, decreasing our sympathetic tone with improvements seen in blood pressure, immune function and digestion (Creswell, 2017). Many studies demonstrate that meditation can change the balance of our autonomic nervous system (the part of our nervous system we don’t control) from that of fight or flight (sympathetic) to that of rest, healing and digestion (parasympathetic) (Koopman, 2011; Amihai, 2015). When our sympathetic nervous system is over activated for days, weeks or months we experience more stress and our bodies experience more inflammation (Bellinger, 2018). Community has also been implicated in longevity. Many years ago there was a town in Pennsylvania where people seemed to have unusual longevity. Harvard researchers looked for many years as to why these people had such unusual longevity. They evaluated the foods, water, genetics among other things and could not find anything that differed significantly from neighboring towns, except, that this town had an unusually strong family and community relationships. Sadly, over the years, as the town modernized and the cohesiveness dissolved, the longevity seen in this town regressed to that of neighboring towns (Egolf, 1992). (For more information on mental wellbeing please see this post.) Lifestyle medicine is meant to be practiced as a form of preventative not reactive medicine. While it is helpful to start lifestyle measures at any point, it is optimal to start early with relative consistency, understanding perfection is not possible. I hope you found this helpful. Amy Savagian, MD References: Amihai, I., Kozhevnikov, M. (2015). The Influence of Buddhist Meditation Traditions on the Autonomic System and Attention. Biomed Res Int. 731579. Published online 2015 Jun 4. doi: 10.1155/2015/731579 Artero EG, Jackson AS, Sui X, Lee DC, O'Connor DP, Lavie CJ, Church TS, Blair SN. (2014). Longitudinal Algorithms to Estimate Cardiorespiratory Fitness: Associations with Nonfatal Cardiovascular Disease and Disease-Specific Mortality. Journal of the American College of Cardiology, Jun, 63 (21):2289-96. doi: 10.1016/j.jacc.2014.03.008. Epub 2014 Apr 2. Bellinger, D.L.1, Lorton, D. (2018). Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)? Int J Mol Sci. 2018 Apr; 19(4): 1188. Published online 2018 Apr 13. doi: 10.3390/ijms19041188 Church TS, Earnest CP, Skinner JS et al. (2007). Effects of Different Doses of Physical Activity on Cardiorespiratory Fitness Among Sedentary, Overweight or Obese Postmenopausal Women With Elevated Blood Pressure: A Randomized Controlled Trial. Journal of the American Medical Association JAMA, 297(19), 2081-2091. https://jamanetwork.com/journals/jama/fullarticle/1108370 Creswell, David J. (2017). Mindfulness Interventions. Annual Review of Psychology. Vol. 68:491-516 (Volume publication date January 2017). First published online as a Review in Advance on September 28, 2016. https://doi.org/10.1146/annurev-psych-042716-051139 Egolf B, Lasker J, Wolf S, Potvin L. The Roseto effect: a 50-year comparison of mortality rates. Am J Public Health. 1992 Aug;82(8):1089-92. doi: 10.2105/ajph.82.8.1089. PMID: 1636828; PMCID: PMC1695733. Hakim et al., (2014). Tumors grow more in sleep deprived mice: Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res. Mar 1;74(5):1329-37. doi: 10.1158/0008-5472.CAN-13-3014 Irwin et al., (1994). “Sleep deprivation reduces natural killer cells: Partial sleep deprivation reduces natural killer cell activity in humans. Psychosomatic Medicine. 56(6):493–498. King et al. (2008). Short sleep duration and incident coronary artery calcification. JAMA 300(24):2859-66. doi: 10.1001/jama.2008.867. Knutson et al. (2007). The metabolic consequences of sleep deprivation. Sleep Medicine Reviews. Volume 11, Issue 3, Pages 163-178. https://doi.org/10.1016/j.smrv.2007.01.002 Koopman, F.A., Stoof, S. P., Straub, R. H. , van Maanen, M. A. , Vervoordeldonk, M. J. , Tak, P. P. (2011) Restoring the Balance of the Autonomic Nervous System as an Innovative Approach to the Treatment of Rheumatoid Arthritis. Mol Med; 17(9-10): 937–948. Published online 2011 May 20. doi: 10.2119/molmed.2011.00065 Ma X, Nan F, Liang H, Shu P, Fan X, Song X, Hou Y, Zhang D. Excessive intake of sugar: An accomplice of inflammation. Front Immunol. 2022 Aug 31;13:988481. doi: 10.3389/fimmu.2022.988481. PMID: 36119103; PMCID: PMC9471313. Mandsager K, Harb S, Cremer P, Phelan D, Nissen SE, Jaber W. (2018) Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Network Open. 1(6):e183605. doi:10.1001/jamanetworkopen.2018.3605 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2707428 Möller-Levet CS et al. 2019 Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome. Proc Natl Acad Sci U S A. Mar 19;110(12):E1132-41. doi: 10.1073/pnas.1217154110. Sheen et al. (1996). Relationships between sleep quality and glucose regulation in normal humans. American Journal of Physiology. Volume 271, No 2, 01 AUG 1996. https://doi.org/10.1152/ajpendo.1996.271.2.E261-E270. Thompson et al., (2011). Colorectal cancer and sleep: Short duration of sleep increases risk of colorectal adenoma. Cancer. Feb 15;117(4):841-7. doi: 10.1002/cncr.25507. https://pubmed.ncbi.nlm.nih.gov/20936662/ Cognitive health is one of our most valuable assets, and a large part of improving healthspan is staving off cognitive decline. The majority of my patients have normal cognitive function and would like to prevent cognitive decline. Why is cognitive health an important focus? Approximately one-third of individuals 65 years and older had dementia or mild cognitive impairment (MCI) [Jama]. According to Alzu.org, a website put together by doctors at Weill-Cornell, up to 40% of MCI and dementia cases are preventable. Interestingly even in those whose dementia may not be entirely preventable, it may be possible to delay the onset symptoms. The area of risk reduction or preventing cognitive decline is very new and it is changing quickly. At our practice we start by taking a good clinical history and looking at the ABC’s (Anthropometrics, blood biomarkers and cognitive functioning. This allows us to do a risk assessment and early intervention. Examples of anthropometrics include BMI, muscle and body fat evaluations. Blood biomarkers include markers of metabolism such as hemoglobin A1c and cholesterol, markers of inflammation such as hs-crp and genetics such as APOe4. The cognitive testing that we perform is using a platform called CNS Vital Signs. This tests areas of cognition such as processing speed, motor speed, memory and executive function. Below is a sample report of this testing.  What can we do to optimize cognitive health? We first need to generally understand the mechanisms that are believed to contribute to cognitive decline. These include: abnormal glucose metabolism, inflammation, oxidative stress, poor trophic factor signaling, and dysfunctional calcium flux (Isaacson et al 2018). In the section below I will discuss each of these and then lifestyle factors that may modulate the mechanisms contributing to cognitive decline.
Abnormal glucose metabolism: Poor glucose metabolism, as seen in diabetes and overfed states such as obesity are known to contribute to insulin resistance at the level of the neuron. Type 2 diabetes is generally a state of hyperinsulinemia (high insulin). This state promotes neuronal inflammation and amyloid deposition. Interestingly, a high-fat, low-carbohydrate ketogenic diet, which is known to limit insulin production, in mice that genetically over-express amyloid beta resulted in a 25% reduction of amyloid burden compared to mice on a standard diet (Van der Auwera et al., 2005). Inflammation: Inflammation is also thought to worsen cognitive function. Studies have shown elevated inflammatory markers in patients with Alzheimer's Disease (AD). To modulate this inflammation, we can consider decreasing dietary sugars, adding in medications or supplements to decrease inflammation and assuring adequate sleep (as sleep deprivation increases biomarkers of inflammation) (Irwin et al., 2006). Social engagement may also play a role in decreasing the risk of AD by improving immune function (Bower et al., 2003, Friedman et al., 2007). Oxidative stress: Patients with AD show many signs of oxidative stress including protein and DNA oxidation as well as lipid peroxidation. The increased oxidation comes from reactive oxygen species (ROS). ROS is important for normal cellular activity, but when there is an imbalance between the production and clearance of ROS the cell undergoes oxidative stress. People with APOe4 have increased markers of oxidative stress (Jofre-Monseny et al., 2008). To decrease oxidative stress, we need to increase the clearance of ROS or decrease the production. Trophic Factors: Trophic factors are basically growth factors. They include molecules such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) that are responsible for brain plasticity and improving cellular survival by preventing activation of the caspase system. BDNF is particularly important in the hippocampus (where memory consolidation occurs). In AD, people have less trophic factors, which in the presence of increased amyloid can lead to neuronal death. (Guo et al., 1997) Amyloid burden: In AD, patients are known to have increased extracellular amyloid. The role of amyloid is not fully understood–some people liken it to scar tissue, but as it accumulates, it causes more inflammation and increases oxidative stress. Interestingly, the oxidative stress, impaired glucose metabolism and inflammation can also lead to more amyloid deposition. Dysfunctional calcium signaling: In AD we see increased intracellular and mitochondrial calcium. These elevated levels can increase ROS, leading to increased oxidative stress, inflammation and amyloid production. Together this leads to increased rates of cell (neuronal) death. Reducing risk should have a multi-factorial approach. Each approach may reduce risk across several domains. For example treating insulin resistance may help with glucose metabolism and downstream effects of inflammation and oxidative stress. Watson and Craft (2003) demonstrated that treating insulin resistance may reduce the risk of AD. Targeted nutrition can reduce the risk of AD through mechanisms of insulin resistance, inflammation and oxidative stress. We can improve insulin resistance by reducing processed sugars and the overfed state. Diets such as a mediterranean or low carb diet have been shown to be helpful. (Scarmeas et al., 2009, Volek et al., 2004). Sleep deprivation has been shown to increase inflammatory cytokines. Assuring adequate sleep will decrease inflammation, improve insulin resistance and help with calcium toxicity. Stress management can help reduce cortisol levels that impact insulin resistance, oxidative stress, trophic factors, calcium toxicity and amyloid burden. Exercise both resistance and aerobic helps with glucose metabolism, insulin resistance, oxidative stress and trophic factors. Hormone replacement may lower amyloid burden and improve trophic factors. Drugs can target inflammation, oxidative stress and amyloid. Supplements may also play a role as it relates to insulin resistance, inflammation, oxidative stress and calcium toxicity. Based on cognitive testing results we may also consider specific interventions that engage executive planning, motor speed, processing speed and more. Alzheimer’s and mild cognitive impairment has a long window of brain changes before any symptoms arise. With monitoring and a targeted lifestyle plan, we can significantly reduce the risk of dementia. References: Alzheimer's Universe. Weill Cornell Medicine. Retrieved November 30, 2022, from https://www.alzu.org/. Bower, J. E., Kemeny, M. E., Taylor, S. E., and Fahey, J. L. (2003). Finding positive meaning and its association with natural killer cell cytotoxicity among participants in a bereavement-related disclosure intervention. Ann. Behav. Med. 25, 146–155. doi: 10.1207/S15324796ABM2502_11 Google Scholar Friedman, E. M., Hayney, M., Love, G. D., Singer, B. H., and Ryff, C. D. (2007). Plasma interleukin-6 and soluble IL-6 receptors are associated with psychological well-being in aging women. Health Psychol. 26, 305–313. doi: 10.1037/0278-6133.26.3.305 Google Scholar Guo, Q., Sopher, B. L., Furukawa, K., Pham, D. G., Robinson, N., Martin, G. M., et al. (1997). Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid β-peptide: involvement of calcium and oxyradicals. J. Neurosci. 17, 4212–4222. Google Scholar Isaacson et al. Mechanisms of Risk Reduction in the CLinical PRactice of Alzheimer’s Disease Prevention. Front. Aging Neurosci., 10 April 2018.doi: 10.3389/fnagi.2018.00096 Google Scholar Irwin, M. R., Wang, M., Campomayor, C. O., Collado-Hidalgo, A., and Cole, S. (2006). Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch. Intern. Med. 166, 1756–1762. doi: 10.1001/archinte.166.16.1756 Google Scholar Jofre-Monseny, L., Minihane, A. M., and Rimbach, G. (2008). Impact of apoE genotype on oxidative stress, inflammation and disease risk. Mol. Nutr. Food Res. 52, 131–145. doi: 10.1002/mnfr.200700322 Google Scholar Manly JJ, Jones RN, Langa KM, et al. Estimating the Prevalence of Dementia and Mild Cognitive Impairment in the US: The 2016 Health and Retirement Study Harmonized Cognitive Assessment Protocol Project. JAMA Neurol. 2022;79(12):1242–1249. doi:10.1001/jamaneurol.2022.3543 Google Scholar Van der Auwera, I., Wera, S., Van Leuven, F., and Henderson, S. T. (2005). A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr. Metab. 2:28. Google Scholar Volek, J. S., Sharman, M. J., Gómez, A. L., DiPasquale, C., Roti, M., Pumerantz, A., et al. (2004). Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women. J. Am. Coll. Nutr. 23, 177–184. doi: 10.1080/07315724.2004.10719359 Google Scholar Watson, G. S., and Craft, S. (2003). The role of insulin resistance in the pathogenesis of Alzheimer’s disease. CNS Drugs 17, 27–45. doi: 10.2165/00023210-200317010-00003 Google Scholar We intuitively know that “fitness” is good for us, but “fitness” is a vague definition. In this post I will discuss how we can measure fitness quantitatively and what fitness levels confer healthspan and mortality benefits. In an article published in JAMA, (Journal of the American Medical Association) the Cleveland Clinic analyzed 23 years of patient data from 1991-2014 (122,007 patients) and evaluated the association of all-cause mortality (death for any reason) and cardiorespiratory fitness. They also evaluated age, gender, race/ ethnicity, and co-morbidities such as diabetes, hypertension, smoking and coronary artery disease (CAD). The findings were remarkable. Their findings on typical risk factors were consistent with what we often see. Having diabetes, coronary artery disease (CAD), smoking, or hypertension conferred approximately a 1.2-1.4X mortality risk or an approximately 20-40% increase risk of death from any cause, but here is the remarkable aspect, being out of shape or having low fitness conferred a 5x mortality risk, in other words a 400% increase risk of death from any cause over any time period. In other words being out of shape was 3 to 4 times worse than smoking, having diabetes or having CAD.  Photo cred:https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2707428 Other groups have published similar findings. In a circulation article published in 2014, Blair et al found that for every 1-MET (Metabolic equivalent) increase in exercise capacity, mortality risk was 12% lower. A study performed by the National Cancer institute evaluated 654,827 individuals and found up to a 4.5 year gain of lifespan with increasing activity. There are a few ways to quantitatively measure fitness. In the Cleveland Clinic study mentioned above they used METs as they had Exercise Treadmill Tests that evaluated peak METs. For those who have never heard of METs or peak METs. A MET is the amount of energy used during any activity. One MET is defined as the amount of oxygen consumed while sitting at rest and is equal to 3.5 ml oxygen per kg body weight x minutes of activity. For reference, walking (3.5–4 mph) is generally around 5 METs. Singles tennis is approximately 8 METs and running a 10 minute mile is approximately 10 METs. As the intensity increases the number of METs increases. Testing a person’s peak METs is one way to establish fitness. Below is a chart of activity and expect METs.  Photo cred: https://oss.adm.ntu.edu.sg/xloh002/activity-range/ Another way to evaluate fitness is the measure the volume of oxygen the body can use, measured in milliliters per kilogram per minute. This measurement is called VO2 max and it is the gold standard for measuring aerobic fitness. Vo2max depends on cardiac output (the pumping ability of the heart stroke volume x heart rate), air exchange in the lungs, blood flow to the muscles and atmospheric oxygen available (due to elevation). Vo2 max is measured by an exercise physiologist as the patient or athlete runs or bikes at progressively harder levels while wearing a mask connected to a machine that evaluates exhaled oxygen and carbon dioxide. Using VO2max we can evaluate relative endurance. To me the data on fitness argues that fitness testing, ideally a VO2max test should be a part of every person's preventative health plan. We need to understand where we are in order to implement a targeted plan to achieve our health goals. References: Ruegsegger GN, Booth FW. Health Benefits of Exercise. Cold Spring Harb Perspect Med. 2018 Jul 2;8(7):a029694. doi: 10.1101/cshperspect.a029694. PMID: 28507196; PMCID: PMC6027933. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027933/ Mandsager K, Harb S, Cremer P, Phelan D, Nissen SE, Jaber W. Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Netw Open. 2018;1(6):e183605. doi:10.1001/jamanetworkopen.2018.3605 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2707428 Blair SN, Kohl HW, Paffenbarger RS, Clark DG, Cooper KH, Gibbons LW. Physical Fitness and All-Cause Mortality: A Prospective Study of Healthy Men and Women. JAMA. 1989;262(17):2395–2401. doi:10.1001/jama.1989.03430170057028 https://jamanetwork.com/journals/jama/article-abstract/379243 Meyers J, Prakash M, Froelicher V et al. Exercise Capacity and Mortality among Men Referred for Exercise Testing. N Engl J Med 2002; 346:793-801. DOI: 10.1056/NEJMoa011858 https://www.nejm.org/doi/full/10.1056/NEJMoa011858 Blair S et al. Age-Specific Exercise Capacity Threshold for Mortality Risk Assessment in Male Veterans. Circulation 2014;130:653–658. https://www.ahajournals.org/doi/full/10.1161/circulationaha.114.009666 https://med.virginia.edu/exercise-physiology-core-laboratory/fitness-assessment-for-community-members/vo2-max-testing/ Moore S et al. Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis. PLOS Medicine. November 6, 2012 https://doi.org/10.1371/journal.pmed.1001335 https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001335  DXA stands for Dual X-ray Absorptiometry. DXA scans help us understand body composition, and I believe a DXA scan can be an important part of a lifestyle plan. It can help us determine the appropriate nutritional and resistance training plan. There are three basic items the DXA evaluates: bone density, fat and lean mass. I am going to discuss all three aspects below: (As an aside there is radiation exposure, however it is very minimal at 1-4 uSv. By comparison, a chest X-Ray (20 uSv) that has about 5-20x more radiation and a CT 10,000x more radiation. ) Bone Density: Bone density is an important metric as it helps us to understand risk of fractures. Fractures particularly hip fractures have a high morbidity and mortality. According to the CDC there are approximately 300,000 hip fractures per year in those 65 years and older [CDC]. Given that there are approximately 56 M Americans who are 65 years or older this gives a crude approximation of 1 hip fracture per every 187 Americans over the age of 65. Of these, studies have found that approximately 25-50% will die over the next year depending on the study. [Cui et al, Schnell et al] This is a staggering number for something that is preventable. For those of us under 65, we should be doing all we can to prevent bone loss. A DXA reports your score for hip, femoral neck and lumbar spine as a T and Z scores. The z-score compares your bone density to others your age. The T-score is the number we care about and it compares your bone density to that of a 30-year-old. A T score of -1.0 or higher is considered normal bone density. A score of -1.0 and -2.5 is in the osteopenia range, and anything under -2.5 is considered the osteoporosis range. Below, you can see a sample report. While osteopenia and osteoporosis are always defined by the T score of -1 and -2.5 at every age, the downtrending lines represent bone density by age (the average and +/-1 standard deviation), in essence showing the expected bone loss by year.  Graphs derived from NHANES & GE Lunar databases. Fat: Fat is reported through several metrics. It is reported as Body Fat%, Fat Mass Index, Visceral Adipose Tissue (VAT) and Android to Gynoid ratio. Let me define each of these for you. Your Body Fat % is the % of your body weight that is fat. The Fat Mass Index is your total body fat (in kilograms) / your height (in meters squared). Visceral Adipose Tissue (VAT) is the amount of fat around your organs. This is the hormonally active fat that plays a role in insulin resistance and inflammation. It has a high correlation to metabolic and cardiovascular disease. The android to gynoid ratio is the ratio of fat around the belly (android) to the fat around the hips (gynoid). Ideal android/ gynoid ratios are <0.8 for women and <1.0 for men. Of all of these fat ratios, the VAT is the most interesting to me, as subcutaneous fat does not seem to have as much metabolic consequence as VAT. When looking at VAT, it is helpful to consider it in terms of age and population percentiles as illustrated in the charts below.  Graphs from LEAD cohort published in Nature Lean Mass: Lean mass is everything that is not fat. This includes muscle, bone, water, connective tissue, skin and organs. The metrics I find important associated with lean mass include: Fat Free Mass Index (FFMI), Appendicular Lean Mass / Height Ratio (ALM/Height2) and Appendicular Lean Mass to BMI. (ALM/BMI). FFMI is the amount of lean mass in kilograms divided by height in meters squared. This can be used to help understand if you are under-muscled relative to others in your age group. Appendicular Lean Mass / Height Ratio (ALMI) is the amount of lean mass in your arms and legs divided by your height2. Low ALM/Ht2 is an important risk factor for low body muscle or sarcopenia. ALMI <5.5 for women and <7 for men are considered to be at risk of sarcopenia, however age based distributions Appendicular Lean Mass/ BMI ratio (ALM/ BMI) is the ratio of lean mass relative to BMI. Sarcopenia for ALM/BMI is considered to start at <0.51 for women and <0.79 for men. ALM/BMI is the most important ratio in my perspective as it considers muscle mass relative to those with a similar weight to height ratios. Lean mass ratios are important in understanding muscle mass. We know that low muscle mass is associated with cognitive decline [Tessier] low bone density [Oubdier, Taniguchi] and those with lower muscle mass appear to die earlier [Bachettini, Srikanthan]. Understanding your muscle mass will help us understand how aggressive you should be with resistance training. When evaluating FFMI and ALMI it is again helpful to consider them in relation to age and distribution.  Graphs from LEAD cohort published in Nature To Summarize DXA scans are helpful in understanding if your fat is metabolically concerning, if you need to gain muscle and how your bone density is faring. I tried to illustrate why it is important to understand each of these factors. If you schedule a dexa try to always schedule with the same machine, avoid calcium supplements for 24 hours before the scan and avoid food for 3 hours before the scan. Hydration can play a role with more water giving higher lean mass reading. DXAs are important because they allow us to benchmark and determine if we need to address muscle mass, VAT or bone density. It allows us to being thinking about nutritional goals and resistance training. I hope this was a helpful, Amy References: Bachettini, N.P., Bielemann, R.M., Barbosa-Silva, T.G. et al. Sarcopenia as a mortality predictor in community-dwelling older adults: a comparison of the diagnostic criteria of the European Working Group on Sarcopenia in Older People. Eur J Clin Nutr 74, 573–580 (2020). https://doi.org/10.1038/s41430-019-0508-8 CDC.gov, Hip Fracture Risks, Retrieved 1/3/23 https://www.cdc.gov/falls/hip-fractures.html#:~:text=Each%20year%20over%20300%2C000%20older,are%20hospitalized%20for%20hip%20fractures.&text=More%20than%2095%25%20of%20hip,2%20usually%20by%20falling%20sideways.&text=Women%20experience%20three%2Dquarters%20of%20all%20hip%20fractures. Cui, Z., Feng, H., Meng, X. et al. Age-specific 1-year mortality rates after hip fracture based on the populations in mainland China between the years 2000 and 2018: a systematic analysis. Arch Osteoporos 14, 55 (2019). https://doi.org/10.1007/s11657-019-0604-3 Oudbier S, Goh J Looijaard S, Reijnierse E, Meskers C, Maier A, Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function, The Journals of Gerontology: Series A, Volume 77, Issue 10, October 2022, Pages 1959–1968, https://doi.org/10.1093/gerona/glac121 Schnell S, Friedman SM, Mendelson DA, Bingham KW, Kates SL. The 1-year mortality of patients treated in a hip fracture program for elders. Geriatr Orthop Surg Rehabil. 2010 Sep;1(1):6-14. doi: 10.1177/2151458510378105. PMID: 23569656; PMCID: PMC3597289. Srikanthan P, Karlamangla AS. Muscle mass index as a predictor of longevity in older adults. Am J Med. 2014 Jun;127(6):547-53. doi: 10.1016/j.amjmed.2014.02.007. Epub 2014 Feb 18. PMID: 24561114; PMCID: PMC4035379. Taniguchi Y, Makizako H, Kiyama R, Tomioka K, Nakai Y, Kubozono T, Takenaka T, Ohishi M. The Association between Osteoporosis and Grip Strength and Skeletal Muscle Mass in Community-Dwelling Older Women. Int J Environ Res Public Health. 2019 Apr 6;16(7):1228. doi: 10.3390/ijerph16071228. PMID: 30959864; PMCID: PMC6480005 Tessier et al. Association of Low Muscle Mass with Cognitive Function During a 3 Year Follow up Among Adults Aged 65 to 86 Years in the Canadian Longitudinal Study on Aging. JAMA Network Open 2022;5(7):e221996. doi:10.1001/jamanetworkopen.2022.19926 . In appointments and in everyday life, people frequently ask about a therapy they heard about on a podcast or morning show. In this post, I want to share how I evaluate new therapies so that you too can systematically evaluate therapies.
As an economics major and prior analyst, I consider the risk to benefit ratio for all therapies that I implement for patients, whether I am assessing risk versus benefit of a surgery or a supplement. I find this analysis particularly helpful when we think about lifestyle and integrative therapies. A simple risk to benefit analysis is very straightforward, but we should not dismiss its power because it seems too simple. I want to walk you through my thought process when I am looking at a new therapy using a recent example I have been considering for a few of my patients. I was recently at an event and met the guy heading up the Virtual Medicine Department at Cedars-Sinai. At Cedars, they are getting great results using virtual reality (VR) in the area of pain management and IBS among other things. I had not spent much time thinking about VR and potential clinical applications, but I was thoroughly intrigued. The idea of using a therapy that is easily accessible to those people who are overbooked and can’t take several hours out of a day to see a doctor or therapist or for those in remote locations this seemed like a great idea. In evaluating this therapy, I wanted to look at a specific indication as there could be many. I thought I would walk the reader through my consideration of VR in the treatment of pain. Let’s first consider the risks (as we must first do no harm). There would be virtually no risk of physical harm in a VR based program, however there is the risk of missing out on alternative therapies, especially if it were to be used exclusively instead of adjunctively. (Alternative therapies for chronic pain include opioids, NSAIDs, Tylenol, supplements, acupuncture, physical therapy and massage among others.) The largest risk in a VR therapy appears to be the cost associated with this novel approach. I then looked at the study data to see if there were any studies on VR and if so if any adverse outcomes were reported. In the studies I evaluated, I did not see any. However, I suppose we could imagine a bad therapy session in VR, like a bad therapist, could leave one feeling worse. When considering the benefits, I also looked to study data to try to understand if there was a significant benefit. In the case of pain management and VR, given the novelty of VR in treatment, the studies are sparse. I found a study looking at acute pain performed at Cedars. In that study, their primary endpoint demonstrated a benefit as reported by pain scores, but not in opioid use. Another study demonstrated reduction in chronic back pain with the use of VR. There is a company called AppliedVR that is FDA authorized and is NIH funded for ongoing studies in pain, which is a promising sign to me. In this scenario, given the minimal risks and potential upside as recognized by many leading institutions, if a patient was struggling with pain that was interfering with their quality of life, I would likely recommend they take a look at this therapy. In this scenario, there is very little risk associated with the proposed intervention, so I am less concerned with the paucity of data, given the largest risk is the cost. Certainly this equation changes for an intervention such as surgery. A surgery has much larger potential risk and therefore must show greater upside. I hope this helps you the next time you are considering a new therapy. All the best, Amy Happy New Year!
I have had many patients emailing and calling to inquire about the COVID vaccine. As of now vaccines are only being administered through long term care facilities, hospitals and hospital clinics. Walgreens and CVS are providing the first phase of vaccines at long term care facilities. Initial distribution outside of long term care facilities and hospitals is currently planned to be through pharmacies based on age, risk and job. Below are the planned phases of distribution. Phase 1A
Currently approved we have the Pfizer-BioN Tech and Moderna vaccines that must be given 3-4 weeks apart. It is currently unknown when phase 1b will begin. It will likely not start until March. Community distribution of the vaccine will be available locally through Albertsons, CVS, Rite-Aid, Target, Walgreens, Costco and Walmart. While all of the above will be offering the vaccines, Albertsons has a sign up link for current updates: https://www.albertsons.com/pharmacy/covid-19.html and CVS has a scheduling tool that will be used once the vaccine is available outside of phase 1a: https://www.cvs.com/immunizations/get-vaccinated Lastly, once the vaccine is available outside of phase 1a, Vaccinefinder.org is also a helpful link to locate the vaccine in any community. For more information please look to official sources such as California for all or the CDC COVID pages for more detailed information. Details are changing rapidly so please check back with the CDC or ca.gov sites above. Lastly for anyone that falls into phase 1B or 1C you will be able to schedule your appointment through LA County Public Health at the appropriate time. Currently, this site only applies to healthcare workers. I have applied to have vaccines for my patients, though this would not likely happen until this summer and higher priority patients will likely be provided the vaccines ahead of that by LA County. . Best, Amy Amy Savagian, MD The CDC has newly released estimates on fatality, hospitalization, and other biologic characteristics of SARS-CoV2. [https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html] The most interesting and potentially reassuring take away is that the CDC’s best estimate now lowers the fatality rate significantly. Below is a table from the CDC listing five scenarios of best, worst and current estimates. The CDC is estimating an overall fatality rate around 0.4%. This is much lower than the up to 13% death rate coming out of Italy. Before going deeper in the numbers, I want to take take a moment to say that while we speak of death rates, and reassurance, each of these statistics is based on people who died, people who had friends and family that love them. My heart goes out to the victims, their friends and family. While the overall death rate is being projected at 0.4%, it is important to note that this is composed of very different rates across age. For those under 50 years of age the average death rate is extremely low, estimated to be 0.05%. For those 50-64 years of age the fatality rate is now thought to be 0.2%, and for those over 65 years the case fatality rate is estimated to be 1.3%. For reference, 0.2% is the fatality rate of measles in the US, one of the vaccines many Americans refuse. [https://www.cdc.gov/vaccines/pubs/pinkbook/meas.html]  To put this further into perspective, I thought it may be useful to look at a person's chance of death of any cause in a given year. This data comes from our government and is called a life table. [https://www.ssa.gov/oact/STATS/table4c6.html]. After the age of 22, the chance of death from any cause in these age groups appears to remain higher than the SARS-CoV-2 estimated fatality rate. For example a 50 year old has a 0.4% chance of dying of any cause and a 0.2% chance of dying of COVID-19. A 70 year old has a 1.88% chance of dying of any cause and a 1.3% chance of dying of COVID-19.  Does this mean we can be completely free of masks and begin holding large events? Sadly, though the fatality rate is low, I don’t think the data otherwise supports that. The hospitalization/ICU rate is what I think should drive many decisions. The CDC estimates hospitalization rate by age from 1.7% to 7.4% with an overall hospitalization rate of 3.4% and of those between 21%- 29% will need to go to the ICU. To illustrate why this is problematic, first consider the US population of 330M, if hospitalization occurs regularly until herd immunity at an estimate of 66%, it means over 5M Americans would need to be hospitalized and over 2M would need ICU care. With only about 63,000 ICU beds [Total less neonatal, pediatric and cardiac ICUs] https://www.aha.org/statistics/fast-facts-us-hospitals in the US and potentially over 15M ICU days needed if the disease ran its course unchecked until we reached herd immunity, excess deaths from SARS-CoV2, stroke, heart attack and other causes would likely occur as care could be unavailable. ICU availability is still our biggest weakness as our ICU’s could be over-run as we saw in Italy.  While I do not think we should be hosting large events, I do not think we should necessarily live in a bubble. I like the Michael Olsterholm approach of attempting to thread the rope through the needle. Slow openings to allow a slower course hopefully preventing excess deaths. I have spent a great deal of time suggesting that we need to be aware of misinformation. Please check references. Social media is not a great platform for an accurate information. Some news outlets may also not be portraying accurate information in order to grab viewers. I find often that news outlets either don't have enough science writers or they attempt to get better viewership by sensationalizing the headline. For great information on SARS-CoV-2. Please consider looking to: CDC: https://www.cdc.gov/coronavirus/2019-ncov/index.html CIDRAP/ Olsterholm Report: https://www.cidrap.umn.edu/covid-19 Hospital and university news updates such as: https://www.hsph.harvard.edu/coronavirus/covid-19-news-and-resources/ I hope this is helpful to you!! ~Amy This Covid update is more optimistic than past updates. The data is changing rapidly and this will change the outlook and recommendations as they become outdated. Today, I am going to discuss how some studies are suggesting that SARS CoV 2 is much more wide spread than we realized which implies a much lower fatality rate. I also want to share information on antibody testing including, which tests are good and the importance of choosing an accurate test. The below graphic is a slide I prepared for a few decision makers on 4/26/20. It evaluates case hospitalization and case fatality rates in LA County vs potential infection hospitalization and fatality rates in LA County. The difference between case and infection rates are based on studies using antibody testing. The chart and graph evaluate the number of hospitalizations and deaths as of 4/26 relative to the potential infections based on the multiples from the NY data and the USC study.  In New York City, the rate of cases vs infections presented by Gov. Cuomo was approximately a multiple of 12, suggesting a much lower infection fatality rate. In Los Angeles, USC completed a study using antibody testing suggesting the we had 28-55 times more infections that cases reported. These are in-line with the Stanford/ Santa Clara study suggesting they had 50X more infections that cases reported. All of these studies optimistically show a much lower hospitalization and fatality rate. Having said that, there are problems with the antibody tests, so we need to evaluate these tests and studies with some healthy skepticism.
For my patients, I am offering the Quest RT-PCR for active symptoms and the Abbott serology test to evaluate prior exposure. The Abbott serology test has been tested internally at Abbott and through a separate commercial lab. From internal testing Abbott reports a sensitivity of 100% and a specificity of 99.5%. The outside lab validated the prior testing suggesting a sensitivity of 100% and a specificity of 99.4%. When evaluating antibody tests, the accuracy is very important as many of these tests are not very accurate. The specificity of these tests is the more important parameter, as you want as few false positives as possible. If you are not a patient of mine, but are interested in antibody testing, the FDA has given letters of authorization to some companies. Click here for a complete list. [https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd] With any of the tests, they should be done in conjunction with a conversation with your doctor. The antibodies show past exposure. The antibody seems to offer a window of protection, though there are questions related to seroconversion and the permanence of immunity after developing antibodies. On a separate note, I wanted to include some educational links to excellent talks on SARS-CoV-2. The first is by Dr. Olsterholm from the MN Center of Infectious Disease Research and Policy (CIDRAP) He has 5 excellent podcasts thus far and many webinars available at this site. https://www.cidrap.umn.edu/covid-19/podcasts-webinars The second excellent educational talk on SARS-CoV-2 is by Dr. Pamela Bjorkman a Cal-tech professor whose lab is currently evaluating the virus. https://www.youtube.com/watch?v=OBcc_dk9Q9U Be well, Amy Let’s start with good news. In California, we have definitely “flattened the curve.” We are approximately 90% below my projections from the LAC data from 3/22 and 3/28. Our doubling time has significantly increased, and we are off our exponential curve.  I have been postponing putting out this aspect of my analysis for a week now. Everyday things seem to change, and I hoped my analysis would lead me elsewhere. I want to spend a minute discussing what flattening the curve means, what different aspects of the curve means and why I think we will have periods of self isolation/ social distancing and re-socialization over at least the next year. The curve represents cases over time. The area under the curve represents the total number of cases. By flattening the curve, we prevent hospitals from being overwhelmed. But it doesn’t mean we ”eradicate” the disease. We live in a globalized society where international travel still occurs and people can travel state to state. If we don’t want to overwhelm the medical system and the number are correct, flattening the curve means we push out our time-line. It means this ends by one of three ways, we have a vaccine, we have an effective treatment or we reach herd immunity (which is thought to occur when about 2/3’s of the population has had the disease). Herd immunity, assuming the numbers are correct is several years away. I think we will have a vaccine or treatment first. So what does this mean? I think it means we will go through multiple periods of social-distancing/ self isolation and re-socialization. I’m hoping our numbers are wrong and that we are significantly underestimating the number of cases we have had. There are two main factors that give me hope. In Iceland, half the people that have tested positive were asymptomatic and if Covid began in China in November and it has the transmissibility that it seems to have, hopefully many more people have had it than have realized it. Let's walk through a scenario below of how LA County could reach herd immunity without overwhelming the system, and you will see why I think we will have a vaccine or treatment before herd immunity and why this won't be over in a few months, but we will likely see multiple cycles of social distancing and re-socialization.  We know that LA County has 10.1M people this means we need about 6.7M cases of covid to reach herd immunity. If we assume 5% of cases need a ventilator that means we will have 336,602. people needing a vent. Average duration on vent has been variable depending on data-sets, but let's assume the average person who needs a vent requires it for 12 days. 336,602 x 12 is about 4M vent days required. Gov. Newsom has called for 10,000 vents in CA, that means we should have about 2500 in the LA area. If we divide 4M vent days by 2500 vents we will get the number of days required to reach herd immunity without overwhelming the system. The answer is about 4 years. That assumes we have our numbers of cases correct, which is a big if. Harvard public health came out yesterday suggesting a similar scenario, though I am sure they had a much more eloquent model. What this means if these numbers hold is that we have a long winter ahead, but with social distancing, we can prevent the system from being overwhelmed.
Be well, Amy Like most American's COVID-19 has my attention. I am mainly looking to the WHO and CDC for my information. Sadly, I feel like many of our news outlets are more interested in grabbing views than presenting balanced information.
What we know for sure, based on the Chinese data posted on the CDC website as of 3/11/20. 1. For those under 50, the mortality rate is very low 0.2-0.4% . 2. Across all ages (including 80 year olds) those people with no chronic illnesses also had a low mortality rate of 0.9%. 3. People over 80 years old had the highest death rate at 14.8% 4. Of confirmed COVID-19 patients in China as of Feb 11, 2020, only 2.1% were aged <20 years, and no deaths were reported among those <10 years of age . 5. An overall mortality rate of 2.3% has been reported among confirmed cases of COVID-19 in China. However, this is likely over-estimated as the majority of these cases were among hospitalized patients. (That means the denominator - the total number of case- likely did not include people that had mild symptoms and did not get tested) Taken together, this means we need to be extremely protective of our elders and those with chronic conditions, but the average American does not need to panic. Signs & Symptoms: According to the CDC, frequent signs and symptoms of patients admitted to the hospital include fever (77–98%), cough (46%–82%), myalgia or fatigue (11–52%), and shortness of breath (3-31%) at illness onset. The incubation period may range from 2-14 days. Transmission: Thought to be droplet. This means that the virus sits on tiny water drops that are expelled with a cough or sneeze. It is not thought to be airborne or aerosolized at this time. People that most need masks are those who are sick and health care workers. Those who are healthy do not need to wear masks unless they are caring for someone who is sick. Virus Spread/Transmission: The virus is spread mainly from person-to-person, between people who are in close contact with one another (within about 6 feet). It is spread through respiratory droplets produced when an infected person coughs or sneezes. These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs. What we can all do. 1. Wash hands often and with soap (for 20 seconds- you can sing twinkle twinkle little star and this is about 20 seconds) or use hand-santizer with 60% alcohol. 2. Avoid touching eyes, nose and mouth with unwashed hands. 3. If COVID-19 is spreading in your community keep at least 6 feet between you and others. 4. Clean and disinfect commonly touched surfaces daily. This includes tables, doorknobs, light switches, countertops, handles, desks, phones, keyboards, toilets, faucets, and sinks. 5. For those that want to boost immune response to RNA viruses like influenza and corona viruses, there is a paper by Mark McCarty and James DiNicolantanio that outlines mechanistically how the following nutraceuticals taken daily as prevention may be beneficial. Selenium 50-100mg Zinc 30-50mg Elderberry 600-1500mg Lipoic Acid 1200-1800mg Glucosamine 3000mg Spirulina 15g Yeast beta glutamates 250-500mg Though, as always speak to your doctor before starting any supplement regimen. Going to the doctor's office office. If you have a mild upper respiratory infection you should stay at home. If you need to be seen with an upper respiratory infection, please call ahead and let us know so that we can quickly get you into a room and take appropriate preventative actions without exposing other patients. |
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