Soy, billed as a healthy alternative to meat and dairy, its impact on a variety of health conditions, including cancer and heart disease, has been hotly debated. The increasing emphasis on plant-based diets has made it more important than ever to understand whether soy should be celebrated for its health benefits or consumed with caution. Culinary Medicine by Lori A Smolin, PhD and Mary B Grosvenor, MS, RD Contributor Stefanie Schwartz, MS, RD, CDN Soybeans are a legume that have been part of the human diet for over 7,000 years.[1] Soybean products such as soymilk, tofu, and tempeh have their origins in Asia and these traditional foods, along with some modern soy products, are becoming more popular in the United States. You can sub soymilk for dairy in your morning coffee, enjoy a soy-based burger for lunch, toss tofu into your dinner stir fry, and snack on edamame. While soy is billed as a healthy alternative to meat and dairy, its impact on a variety of health conditions, including cancer and heart disease, has been hotly debated. The increasing emphasis on plant-based diets has made it more important than ever to understand whether soy should be celebrated for its health benefits or consumed with caution. [2,3] Soy Nutritional Contributions and Concerns Soy is high in protein; it is considered equivalent to animal protein in protein quality, making it a valuable addition to vegan diets. It is cholesterol free and low in saturated fat. Soy provides a good source of fiber, contains omega-3 polyunsaturated fatty acids, is rich in the vitamins thiamin, folate, and vitamin K and provides minerals including calcium, iron, magnesium, and potassium. In addition, it contains phytochemicals including isoflavones, which are a type of phytoestrogen (phyto=plant), tocopherols, carotenoids, and phytosterols. As discussed in the sections below, soy has the potential to provide many health benefits but it is also one of the most common food allergens.[4]   Foods containing soy must include it in the ingredient list and often highlight it at the end of the list with a statement such as: “Contains soy”.  Soy may also interfere with the action of some medications. For example, soy can reduce the absorption of levothyroxine used to treat hypothyroidism. Those taking this medication need to avoid soy one hour before or within up to four hours after taking the medication or if they eat soy consistently, their dose of levothyroxine should be adjusted to account for the interference.[3] Soy can also interfere with some chemotherapy drugs and hormone-based cancer treatments; patients taking these medications should check with their oncologist before consuming soy.[3] Breast Cancer The relationship between soy and breast cancer has been highly debated.  Much of the controversy has to do with how the isoflavones in soy affect estrogen activity in the body. Some types of breast cancer cells have proteins called estrogen receptors on their surface. When estrogen binds to these receptors it stimulates the cancer cells to grow.  Isoflavones are structurally similar to estrogen so can bind to estrogen receptors in the body.[3] The physiologic effect of this binding is variable, in some situations having weak estrogenic effects and in others blocking estrogen activity.[3] In the case of breast cancer, epidemiological evidence supports an anti-estrogenic role for soy isoflavones; soy consumption is inversely associated with cancer incidence and deaths.[5] However, over the years challenges have been made to the proposed breast cancer benefits of soy. In the late 1990s studies done on mice suggested that genistein, an isoflavone in soy, stimulated the growth of existing breast cancer cells.[6] This led clinicians to recommend that breast cancer patients avoid soy. However, since then it has been determined that the results of these studies cannot be applied to humans because mice metabolize genistein very differently. Human studies have found that consuming soybeans or isoflavones lowers the risk of breast cancer and in breast cancer survivors, lowers the risk of recurrence and death.[5,7] Thus, as our understanding has evolved, so have recommendations. It is currently the position of the American Cancer Society, the American Institute for Cancer Research, and the World Cancer Research Fund International that soy foods can be safely consumed by women with breast cancer.[3] Prostate Cancer Prostate cancer is another hormone-dependent cancer that may be affected by the isoflavones in soy. Epidemiology supports the benefits of soy; the incidence of prostate cancer is much lower in Asian countries where soy intake is high. Asian men who move to the United States and adopt a Western diet have an increased risk of prostate cancer, but those who continue to consume a traditional diet high in soy do not.[8] Although there is evidence to suggest that soy intake reduces the risk of prostate cancer, the data are currently too inconsistent to make conclusive recommendations.[3] Heart Health Lowering blood levels of LDL cholesterol is an important strategy for reducing the risk of cardiovascular disease (CVD). The cholesterol-lowering properties of soy protein have been studied for decades. In the 1990s, data supporting a cholesterol-lowering effect of soy prompted the FDA to allow a health claim on food labels highlighting the benefit of soy protein in reducing the risk of heart disease. But the hypocholesterolemic effects of soy protein became controversial when subsequent studies did not find soy protein to have a significant cholesterol-lowering effect.[9] Today, meta-analyses support a modest, yet clinically relevant, cholesterol-lowering effect for soy protein.[3] Most of the studies on the cholesterol-lowering properties of soy have investigated the effects of the protein in soy. But whole soy has other nutritional properties, such as being low in saturated fat and high in polyunsaturated fat and fiber, that could contribute to its cholesterol-lowering effects.[9] A long-term epidemiological study found that replacing red meat with soy foods, beans, and nuts was associated with a 14% lower risk of heart disease.[10] Soy may also have other physiological effects that reduce CVD risk.  Soy intake may help to reduce blood pressure.[9] The mechanism is not known and in most studies the reduction is modest, but even modest blood pressure lowering can have a significant impact on CVD risk. Soy intake is also negatively associated with the risk of type 2 diabetes, an important risk factor for CVD.[11] Hot Flashes The fluctuating levels of estrogen and progesterone that occur with menopause cause  hot flashes and other menopausal symptoms. Increasing intake of soy isoflavones, which bind to estrogen receptors, has been hypothesized to help reduce hot flashes. Women in Asian countries have less frequent hot flashes and higher blood levels of isoflavones than women in the US, but it is unclear whether the less frequent hot flashes are due to soy intake.[12] Reviews of studies on the effect of supplemental isoflavones on hot flashes found conflicting results. This may be due to the use of different types of isoflavones in different trials.[3,13,14] For example, clinical trials using supplements derived from whole soybeans generally support its effectiveness at reducing hot flashes, while those using supplements made from the germ portion of the bean do not.[3] The fact that isoflavones are safe and have other health benefits makes them an appealing alternative to hormone therapy for hot flashes.[13] Osteoporosis Osteoporosis risk increases dramatically in postmenopausal women when estrogen levels drop. A meta-analysis found supplements of soy isoflavones or consumption of soy protein or soy foods resulted in significant improvement in bone mineral density of the spine, hip, and femoral neck in menopausal and perimenopausal women.[15] However, this is clinically significant only if it results in a reduction in bone fractures. A meta-analysis of studies investigating the association of soy food intake with bone fractures found that intake correlated with a reduced fracture risk in women but the association was not significant in men.[16] More information is needed before recommending isoflavones to improve bone health, but including soy foods, which are a source of isoflavones and protein, and are often fortified with calcium, may have benefits for those with concerns about bone loss. Cognitive Function Some cognitive decline occurs in adults as they age but decline that interferes with daily life is not normal.[17] In postmenopausal women evidence suggests that low levels of estrogen may contribute to impaired cognitive function.[2] Soy isoflavones are thought to exert beneficial effects on cognition function through their estrogen-like activity. [18]  Although the results of both observational studies and randomized controlled trials evaluating the effects of isoflavones on cognitive decline have been inconsistent, recent meta-analysis support the potential of isoflavones in soy foods to reduce cognitive decline and dementia.[3,18] Bottom Line Soy has been extensively studied for its impact on various health conditions, often with conflicting results. Some of the inconsistences may be due to differences in the type of study, the study population, and the amount and type of soy used. Despite continuing controversy, there is significant evidence that soy intake has protective effects against breast and prostate cancers and heart disease. In addition, there is data supporting a beneficial impact of soy on the symptoms of menopause, osteoporosis, and cognitive function. Although there is still insufficient evidence to make specific recommendations for intake of soy in foods or supplements, it is safe for healthy individuals to consume soy products such as soymilk, meat alternatives, tofu, edamame, and tempeh. When added to the diet, soy is a nutrient-dense source of high-quality protein that can provide health benefits, particularly when used as a substitute for red or processed meat.[3] References [1] Lee GA, Crawford GW, Liu L, Sasaki Y, Chen X. Archaeological soybean (Glycine max) in East Asia: does size matter? PloS One. 2011;6(11):e26720. doi:https://doi.org/10.1371/journal.pone.0026720 [2]Harvard School of Public health. Straight Talk about Soy. The Nutrition Source. Published August 6, 2018.  https://www.hsph.harvard.edu/nutritionsource/soy/ [3] Messina M, Duncan A, Messina V, Lynch H, Kiel J, Erdman JW. The health effects of soy: A reference guide for health professionals. Frontiers in Nutrition. 2022;9:970364. doi:https://doi.org/10.3389/fnut.2022.970364 [4] Center for Food Safety and Applied Nutrition. Food Allergies. FDA. Published November 3, 2020. https://www.fda.gov/food/food-labeling-nutrition/food-allergies ‌[5] Jung Hyun Kang, Dong Z, Seung Ho Shin. Benefits of Soybean in the Era of Precision Medicine: A Review of Clinical Evidence. Journal of microbiology and biotechnology. 2023;33(12):1552-1562. doi:https://doi.org/10.4014/jmb.2308.08016 [6] Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. (2001) 61:5045–50. [7] Qiu S, Jiang C. Soy and isoflavones consumption and breast cancer survival and recurrence: a systematic review and meta-analysis. European Journal of Nutrition. 2018;58(8):3079-3090. doi:https://doi.org/10.1007/s00394-018-1853-4 [8] van Die MD, Bone KM, Williams SG, Pirotta MV. Soy and soy isoflavones in prostate cancer: a systematic review and meta-analysis of randomized controlled trials. BJU International. 2014;113(5b):E119-E130. doi:https://doi.org/10.1111/bju.12435 [9] Messina M. Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature. Nutrients. 2016;8(12):754. doi:https://doi.org/10.3390/nu8120754 [10] Al-Shaar L, Satija A, Wang DD, et al. Red Meat Intake and Risk of Coronary Heart Disease among US men: Prospective Cohort Study. BMJ. 2020;371:m4141. doi:https://doi.org/10.1136/bmj.m4141 [11] Zuo X, Zhao R, Wu M, Wan Q, Li T. Soy Consumption and the Risk of Type 2 Diabetes and Cardiovascular Diseases: A Systematic Review and Meta-Analysis. Nutrients. 2023;15(6):1358. doi:https://doi.org/10.3390/nu15061358 [12] Li L, Lv Y, Xu L, Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. British Journal of Clinical Pharmacology. 2015;79(4):593-604. doi:https://doi.org/10.1111/bcp.12533 [13] Chen LR, Ko NY, Chen KH. Isoflavone Supplements for Menopausal Women: A Systematic Review. Nutrients. 2019;11(11):2649. doi:https://doi.org/10.3390/nu11112649 [14] Taku K, Melby MK, Kronenberg F, Kurzer MS, Messina M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity. Menopause: The Journal of The North American Menopause Society. 2012;19(7):776-790. doi:https://doi.org/10.1097/gme.0b013e3182410159 [15] Akhlaghi M, Ghasemi Nasab M, Riasatian M, Sadeghi F. Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials. Critical Reviews in Food Science and Nutrition. Published online July 10, 2019:1-15. doi:https://doi.org/10.1080/10408398.2019.1635078 [16] Mohsen Akhavan Zanjani, Rahmani S, Sanaz Mehranfar, et al. Soy Foods and the Risk of Fracture: A Systematic Review of Prospective Cohort Studies. Complementary medicine research. 2021;29(2):172-181. doi:https://doi.org/10.1159/000519036 [17] CDC. Subjective Cognitive Decline — A Public Health Issue. www.cdc.gov. Published March 25, 2019. https://www.cdc.gov/aging/data/subjective-cognitive-decline-brief.html#:~:text=Subjective%20Cognitive%20Decline%20(SCD)%20is [18] Cui C, Birru RL, Snitz BE, et al. Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews. 2019;78(2):134-144. doi:https://doi.org/10.1093/nutrit/nuz050

Pedal Through Pain - Study Links Cycling to Reduced Knee Osteoarthritis Risk Medical News A study published in April 2024, of 2,607 subjects with a mean age of 64.3 years, investigated the effect of bicycle riding on the development of knee osteoarthritis. They looked at three different endpoints, the prevalence of radiographic knee osteoarthritis, frequent knee pain, and symptomatic radiographic knee osteoarthritis.  51.6% of the subjects had a history of bike riding.  52.4%, 25.2%, 12.2%, and 10.2% identified bicycling in one, two, three, and four different time periods of their lives respectively.  The division of ages was 12–18, 19–34, 35–49, and greater than 50 years old. Compared to non-bicyclers, bicyclers had 17% less risk for frequent knee pain, 9% less risk of radiographic osteoarthritis and 21% less risk of symptomatic radiographic osteoarthritis.  The reduction in symptomatic osteoarthritis was 17% for those that bicycled for only one period in their lives versus a 38% risk reduction for those that had bicycled in three periods of their lives and a 43% reduction for those that had bicycled in all four time frames in their lives. Comments: In this study people who bicycled had a lower prevalence of radiographic knee osteoarthritis, frequent knee pain, and symptomatic radiographic knee osteoarthritis, than non-bikers.  The more time one biked for, the higher the risk reduction.  A logical conclusion from this interesting study and the authors’ conclusion is that bicycling may be favorable to knee health, which may be true. However, there are some limitations in interpreting this data.  Another possibility to be considered is that people with knee problems may be less likely to continue bike riding while those with less knee pain or pathology are more likely to continue bike riding, rather than bike riding itself having a protective effect.  Finally, in the Osteoarthritis Initiative Database that was used for the study, 2,189 subjects were excluded for various reasons; not returning for a 96-month visit, not filling out the historical form, or not having x-rays of the knee to examine.  Eliminating subjects due to protocol violations is very common in medical research, but in this case almost 46% of the potential subjects were excluded.  There is no way of knowing, if those subjects had been included, whether the results would or would not have been the same. Lo GH  et al. Bicycling over a Lifetime Is Associated with Less Symptomatic Knee Osteoarthritis: Data from the Osteoarthritis Initiative. Medicine & Science in Sports & Exercise ():10.1249/MSS.0000000000003449, April 11, 2024. Retrieved from: https://journals.lww.com/acsm-msse/abstract/9900/bicycling_over_a_lifetime_is_associated_with_less.512.aspx

Are you ready to try entomophagy? Culinary Medicine By Mary B Grosvenor, MS, RD and Lori A Smolin, PhD Cicadas! For the first time since Thomas Jefferson was President, two broods of cicadas, a 17-year and a 13-year brood, are emerging together this year. Buzzing, flying, falling cicadas are overwhelming much of the southeastern and midwestern United States.[1]  While some consider the cicadas a nuisance, others see them as a potential meal. Racoons, birds, fish, and even bears feast on them.  Cicadas and other insects are also enjoyed by humans, primarily in Asia, Africa, and Latin America.[2,3] Though not particularly popular in the United States, you can buy a bag of “mixed bug” trail mix on Amazon or a cup of savory chili-lime salt grasshoppers at a Seattle Mariners game! It turns out that edible insects are a highly nutritious and environmentally friendly option for addressing the global food crisis.[4] Who Eats Bugs? Entomophagy, the scientific term for eating insects, has been practiced by humans for millennia.[3] Today there are more than 1000 insect species that are eaten by some 2 billion people worldwide. The most commonly consumed are ants, crickets, grasshoppers, beetles, termites, cicadas, dragonflies, and grubs.[5] In many regions around the world edible insects make an important nutritional contribution to the local diet. [6] In fact, to help meet the planet’s rising demand for food, the United Nations has recommended increasing insect farming and consumption. [4] Insects can be eaten whole or processed into powders, pastes and granules used in snack foods like protein bars and cookies and in additives used to enhance the nutrient content of other foods.[2] For most of us raised in Western society, insects are seen as disease-carrying pests, rather than appealing snacks. But many more of us may be eating many more of them as as farming methods and marketing strategies improve to increase their appeal. Nutritional, Health, and Environmental Impact of Edible Insects While nutrient content varies with the species and stage of development, generally insects provide a readily absorbable source of high-quality protein along with healthy monounsaturated and polyunsaturated fatty acids, fiber, vitamins, and minerals.[7]  Cicadas, for example, provide more than twice the protein as an equivalent serving of beef and are a great source of fiber.[6,7] Insects are comparable to meat in terms of niacin and thiamin content and are higher in vitamin C, vitamin E, and riboflavin. They contain small amounts of vitamin B12, a concern for vegans, but insects are animals so are not included in a vegan diet. [8] Insects also provide more calcium, zinc, copper, and manganese than meat.[9]  As with other foods, how they are prepared can impact their nutrient content. [6] For example, frying insects in animal fat will add saturated fat and boiling them can cause the loss of some vitamins and minerals. Insects also contain bioactive compounds (the equivalent of phytochemicals in plants) that have been shown in both animal and in vitro studies to have antioxidant, anti-inflammatory, hypotensive, antimicrobial, and immunomodulatory properties.[10] These are properties that have the potential to promote human health, but clinical trials are needed to confirm any roles in preventing or managing chronic disease in humans. Obviously, a meal made from cicadas collected from your yard has a small ecological footprint, but even insects farmed for human consumption are far more environmentally friendly than producing other protein sources. Insect farming requires little land, energy, or water. Production is rapid because insects have short growth cycles. If fed food scraps insects can reduce other wastes, and their excrement is used as fertilizer for plant crops.[ 6,11] Insect farmers domesticate insects to increase their yields and ensure future crops. Farming increases sustainability because catching wild insects can lead to overharvesting, reduce biodiversity, and even advance the risk for extinction.[12] Even large-scale insect farming can have a low carbon footprint when its processes are planned with attention to all stages of feeding, breeding, and harvesting the insects.[7] Safety is always a concern The safety concerns associated with eating insects are similar to those of more common protein sources.  Allergic reactions are possible. Individuals with a shellfish allergy may also have an allergic reaction to insects due to cross-reactivity between insect and shellfish proteins. [13] Physical hazards, such as cricket legs, can pose a choking threat and have the potential to cause injuries to the mouth and gastrointestinal tract of the consumer. Greater concerns are chemical or microbial contamination of the insects or the products made from them. Chemical contamination can occur if insects are exposed to pesticides, heavy metals, and environmental contaminants such as dioxin. Contamination with microbiological hazards such as bacteria, viruses, and parasites can occur at any point during the process of capturing, raising, and processing insects for consumption. To avoid these issues, large-scale producers are often subject to the same food safety regulations that apply to other food manufacturers. [7] Bottom Line Are you ready to try entomophagy? Rationally it makes sense to use this food source. But Americans don’t want to eat insects! [14] One reason is what has been called the “ick” factor; insects don’t fit with our view of what we consider food.  Another is the concern for safety. However, when raised using safe production methods and managed with appropriate regulations, insects may carry fewer risks than other foods in the American diet.[6] If dining on insects is still a reach for you, maybe you could start by slipping some cricket flour into your pancakes. Or perhaps you’d rather just leave them for the birds. Authors’ note: Usually, we provide a recipe to go along with our nutrition updates but in this case, we will leave it to the cicada experts at the University of Maryland Cicada-licious’ Cooking.[15]  Check out their recipes for Shanghai Cicadas, Maryland Cicadas, and Chocolate Covered Cicadas. References [1] Djajapranata C. Biologist Explains Everything to Know About This Year’s Cicadas. Georgetown University. Published May 3, 2024. Accessed May 13, 2024. https://www.georgetown.edu/news/ask-a-professor-cicadas/ [2] Li M, Mao C, Li X, et al. Edible Insects: A New Sustainable Nutritional Resource Worth Promoting. Foods. 2023;12(22):4073. doi:https://doi.org/10.3390/foods12224073 [3] Raheem D, Carrascosa C, Oluwole OB, et al. Traditional consumption of and rearing edible insects in Africa, Asia and Europe. Critical Reviews in Food Science and Nutrition. 2018;59(14):2169-2188. doi:https://doi.org/10.1080/10408398.2018.1440191 [4] Arnold Van Huis. Edible Insects : Future Prospects for Food and Feed Security. Food And Agriculture Organization Of The United Nations; 2013. [5] Insects That Are Regularly Eaten Around The World. WorldAtlas . https://www.worldatlas.com/articles/insects-that-are-regularly-eaten-around-the-world.html [6] Li H, Chumroenphat T, Bunyatratchata A, Boonarsa P, Wrigley C, Siriamornpun S. Chemical composition and nutritional profile of cicada (Meimuna opalifera Walker) at different developmental stages: Implications for functional food applications. Food chemistry X. 2024;21:101081-101081. doi:https://doi.org/10.1016/j.fochx.2023.101081 [7] Conway AJ, Jaiswal S, Jaiswal AK. The Potential of Edible Insects as a Safe, Palatable, and Sustainable Food Source in the European Union. Foods. 2024;13(3):387-387. doi:https://doi.org/10.3390/foods13030387 [8] Elorinne AL, Niva M, Vartiainen O, Väisänen P. Insect Consumption Attitudes among Vegans, Non-Vegan Vegetarians, and Omnivores. Nutrients. 2019;11(2):292. doi:https://doi.org/10.3390/nu11020292 [9] Orkusz A. Edible Insects versus Meat—Nutritional Comparison: Knowledge of Their Composition Is the Key to Good Health. Nutrients. 2021;13(4):1207. doi:https://doi.org/10.3390/nu13041207 [10] Aguilar-Toalá JE, Cruz-Monterrosa RG, Liceaga AM. Beyond Human Nutrition of Edible Insects: Health Benefits and Safety Aspects. Insects. 2022;13(11):1007. doi:https://doi.org/10.3390/insects13111007 [11] Zhou Y, Wang D, Zhou S, Duan H, Guo J, Yan W. Nutritional Composition, Health Benefits, and Application Value of Edible Insects: A Review. Foods. 2022;11(24):3961. doi:https://doi.org/10.3390/foods11243961 [12] Piña-Domínguez IA, Eliel Ruiz-May, D. Hernández-Rodríguez, Zepeda RC, Guiomar Melgar-Lalanne. Environmental effects of harvesting some Mexican wild edible insects: An overview. Frontiers in sustainable food systems. 2022;6. doi:https://doi.org/10.3389/fsufs.2022.1021861 [13] Husain S. Shellfish Allergy: A Complete Guide Food Allergy Institute. Food Allergy Institute. Published June 25, 2022. Accessed May 14, 2024. https://foodallergyinstitute.com/severe-food-allergies/seafood-shellfish-allergy/shellfish-allergy-a-complete-guide/#:~:text=Cross-reactivity%20occurs%20when%20the%20body%20confuses%20proteins%20from [14] Zulkosky C. Are Edible Insects the Future of Alternative Protein? The Food Institute. Published November 7, 2023. https://foodinstitute.com/focus/are-edible-insects-the-future-of-alternative-protein/#:~:text=Edible%20insects%20have%20all%20the [15] “Cicada-licious” Cooking. Maryland Today. Published April 23, 2021. Accessed May 13, 2024. https://today.umd.edu/cicada-licous-cooking-e031e1f4-ee49-4a27-a377-72607b8ed189

May 2024 Study Explores Olive Oil and Dementia Prevention Potential. Medical News In a study published May 2024, with 92,383 subjects, the issue of whether dietary olive oil can reduce the incidence of dementia was investigated.  The data was from two longitudinal studies of health care professionals over 28 years. It was reported that dietary intake of more than 7 grams of olive oil per day (about ½ of a tablespoon)  reduced the incidence of dementia-related deaths by 28% overall compared to those that rarely or never or rarely ingested olive oil. The risk reduction in women was 33% and was 13% in men. They calculated that replacing 5 g/d (grams per day) of mayonnaise with 5 g/d of olive oil could reduce dementia-related deaths by 14% and substituting 5 g/d of olive oil for 5 g/d of margarine could reduce the risk by 8%. A genetic variant, apolipoprotein E ε4 (APOE4) allele can interfere with lipid and glucose metabolism and may increase the risk of dementia was tested for in a subset of 27,296 subjects.  Subjects who were homozygous for APOE4 (have the variant on both sets of chromosomes) were 5.5 to 9.4 times more likely to have dementia-related death than those without the mutation.  Heterozygotes (only have the variant on one chromosome) were 1.7 to 2.3 times more likely to have dementia-related death. After adjusting the data for this, the reduction in dementia-related death from the use of olive oil was still found to be present. Summary This large longitudinal study found that the ingestion of daily olive oil over 28 years reduced the overall incidence of dementia-related death by 28%, more in women than men. Substitution of olive oil for margarine or mayonnaise was calculated to also reduce risk. Although subjects with the APOE4 genetic variant had higher baseline risks of dementia, when the data was adjusted for those subjects, risk reduction for dementia-related death was still found in the olive oil group. References Tessier A, Cortese M, Yuan C, et al. Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death. JAMA Netw Open. 2024;7(5):e2410021. Retrieved from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2818362

May 2024 Study Explores Alzheimer's Risk in APOE4 Homozygotes Medical News A study published in May, 2024, using data from 10,039 individuals and 3,297 brain donors from the National Alzheimer’s Coordinating Center looked at the risk of Alzheimer’s disease in APOE4 genetic variant homozygotes. APOE4 homozygotes have been reported in past studies to have a lifetime risk for Alzheimer’s disease of up to 60% by age 85.  The authors reported that this study compared APOE4 homozygotes to subjects who had the more common APOE3 variant that is not associated with Alzheimer’s disease. On average, Alzheimer’s disease symptoms for the APOE4 group started at age 65.6, produced cognitive defects at age 71.8, dementia at age 73.6 and death at 77.2, about 7–10 years earlier than those who developed Alzheimer’s disease and did not carry the APOE4 variant.  APOE4 homozygotes had significantly higher levels of Alzheimer’s biomarkers in their blood from age 55 on, compared to normal variant individuals.  By age 65, over 90% had abnormal amyloid levels in their cerebrospinal fluid and 75% had positive scans for amyloid.  The authors also stated that APOE4 homozygotes and heterozygotes have very different clinical outcomes and genetic risk profiles and should not be thought of as a single entity. Summary Besides being found to have an increased risk for dementia-related death in the previously discussed olive oil study, APOE4 homozygote individuals are at a very high risk for Alzheimer’s disease.  The authors suggested that it is in fact more than just a risk factor but should be considered a genetic form of Alzheimer’s disease.  Although there are racial and geographical variations, the incidence of APOE4 homozygotes is thought to be about 2% of the population.  The study’s authors stated that their findings pointed to the need for individualized prevention strategies and more research to find effective treatments. Resources Fortea, J., Pegueroles, J., Alcolea, D. et al. APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease. Nat Med (2024). Retrieved from: https://www.nature.com/articles/s41591-024-02931-w#citeas

Understanding Ehrlichiosis: Symptoms, Diagnosis, and Treatment Ehrlichiosis, caused by bacteria carried by ticks, presents varying symptoms and requires prompt diagnosis and treatment. What you need to know to understand Ehrlichiosis symptoms, disgnosis, and treatments. This article explores is part one of a four part CME series “ Diagnosis and Treatment of Four Tickborne Diseases: Lyme Disease, Ehrlichiosis, Anaplasmosis and Babesiosis ” . EHRLICHIOSIS (Part 2) by Stuart M. Caplen, MD Ehrlichiosis is caused by three bacteria, Ehrlichia chaffeensis, Ehrlichia ewingii, or Ehrlichia muris eauclairensis . The majority of reported cases are due to infection with E. chaffeensis. E. chaffeensis and E. ewingii are carried by the lone star tick, Amblyomma americanum, found primarily in the south-central and eastern United States. E. muris eauclairensis is carried by the blacklegged tick, Ixodes scapularis, but despite this tick’s wide distribution has only been reported in Wisconsin and Minnesota.[26] In 2018, there were 1,799 cases of E. chaffeensis reported to the CDC. The other Ehrlichia infections are much rarer, with only 218 cases of E. ewingii ehrlichiosis reported to CDC from 2008–2018, and about 115 cases of ehrlichiosis caused by E. muris eauclairensis reported since its discovery in 2009.[27] Ehrlichia are small, gram-negative bacteria, round or ellipsoidal in shape. They preferentially invade monocytes, macrophages, and neutrophils. In all of these cell types they occupy cytoplasmic vacuoles, usually in bacterial microcolonies known as morulae.[28] Early Signs and Symptoms of Ehrlichiosis [29] Signs and symptoms of ehrlichiosis typically begin within 5 to 14 days after the bite of an infected tick. Early signs and symptoms are usually mild or moderate and may include: Fever, chills Severe headache Muscle aches Nausea, vomiting, diarrhea, loss of appetite Gastrointestinal symptoms are less common in patients with E. ewingii ehrlichiosis than with the other two species. Confusion Rash A rash develops in up to 60% of children, and less than 30% of adults, and typically begins about 5 days after symptom onset. The rash usually spares the face, but in some cases may spread to the palms of hands and soles of feet. The rash associated with E. chaffeensis infection may range from maculopapular to petechial in nature and is usually non-pruritic. Rash is infrequent in cases of E. muris eauclairensis. Late Symptoms of Ehrlichiosis[29] If treatment is delayed and the ehrlichiosis infection is allowed to continue, the disease may become severe. Severe illness may involve: Meningitis, meningoencephalitis, and other central nervous system involvement (20% of patients) Acute respiratory distress syndrome Toxic shock-like or septic shock-like syndromes Renal failure Hepatic failure Coagulopathies E.chaffeensis generally is the more serious illness, as neither E. ewingii nor E. muris eauclairensis infections have been associated with fatalities. The case fatality rate of E. chaffeensis is about 1%. Laboratory Findings in Ehrlichiosis[28] General laboratory findings in ehrlichiosis can include absolute leukopenia, thrombocytopenia, and moderately elevated hepatic transaminases. Anemia is reported in about half of patients, but generally occurs later in the course of the illness. Testing for Ehrlichiosis[29] Microscopic examination of a blood smear may reveal morulae, which are microcolonies of Ehrlichiae in the cytoplasm of white blood cells. E. chaffeensis most commonly infects monocytes while E. ewingii more commonly infects granulocytes. No specific target cell has been identified for E. muris eauclairensis. A concentrated buffy-coat smear can improve the yield of morulae evaluation compared with a standard blood smear. When positive, the diagnosis can be made relatively easily, but unfortunately blood smear examination is relatively insensitive for detecting the disease. If a bone marrow biopsy is performed as part of the investigation of cytopenias, immunostaining the bone marrow biopsy specimen to look for morulae, may help diagnose ehrlichiosis. Organ biopsies, if done for other purposes may also show evidence of morulae. The indirect immunofluorescence antibody (IFA) assay for IgG, is the test most widely performed to diagnose ehrlichiosis. IgG IFA assays should be performed on paired acute and convalescent serum samples collected 2–4 weeks apart with a fourfold increase or decrease in the titers needed to be interpreted as positive. Antibody titers are frequently negative in the first week of illness. Ehrlichiosis cannot be confirmed using a single acute set of antibody results. IgM IFA assays are also offered by reference laboratories but are not necessarily indicators of acute infection, and appear to be less specific than IgG antibodies. It is therefore not recommended to use IgM antibody titers alone for diagnosis. Polymerase chain reaction (PCR) amplification can be performed from whole blood specimens. PCR is most sensitive in the first week of illness and decreases in sensitivity following the administration of appropriate antibiotics (within 48 hours). Although a positive PCR result is helpful, a negative result does not rule out the diagnosis, and treatment should not be withheld due to a negative result if ehrlichiosis is clinically suspected. PCR may also be used to amplify DNA in solid tissue and bone marrow specimens. Culture of Ehrlichia species is only available at specialized laboratories, and routine hospital blood cultures cannot detect the organism. Treatment of Ehrlichiosis [30] As opposed to Lyme disease, post-tick bite antibiotic prophylaxis is currently not recommended to prevent ehrlichiosis. Doxycycline is the treatment of choice for ehrlichiosis if the diagnosis is suspected, for patients of all ages, including children <8 years. Doxycycline is most effective at preventing severe complications from developing if started within the first week of illness. The recommended dosage for is doxycycline for adults is 100 mg every 12 hours, and for children under 45 kg (100 lbs.) the dose is 2.2 mg/kg body weight given twice a day. Dental staining in children has been a concern with doxycycline, but a study of 58 children under eight years of age with Rocky Mountain spotted fever, found no evidence of dental staining from doxycycline treatment.[31] Patients with suspected ehrlichiosis should be treated with doxycycline for at least 3 days after the fever subsides, and there is evidence of clinical improvement, typically in 5-7 days. In cases of life-threatening allergies to doxycycline, severe doxycycline intolerance, and in some pregnant patients for whom the clinical course of ehrlichiosis appears mild, physicians might consider alternate antibiotics. Rifampin appears effective against E. chaffeensis in a laboratory setting, but has not been evaluated as an alternative therapy in a clinical setting. Caution is advised when exploring treatments other than doxycycline, as other tickborne co-infections like Lyme disease or Rocky Mountain spotted fever may go intreated. An infectious disease consult is recommended when treating the pregnant patient. #InfectiousDisease #ticks More TICK-BORNE Disease articles: Lyme  | Anaplasmosis  | Babesia The CME version of this article" Diagnosis and Treatment of Four Tickborne Diseases Lyme disease, Ehrlichiosis, Anaplasmosis and Babesiosis "  is available for the medical community with an online CME test in the APP. REFERENCES [3] Tickborne Diseases of the United States, CDC, last reviewed September 22, 2020. Retrieved from: https://www.cdc.gov/ticks/tickbornediseases/overview.html [15] Tickborne Diseases of the United States, CDC, 5th edition 2018. Retrieved from: https://www.cdc.gov/ticks/tickbornediseases/TickborneDiseases-P.pdf [15A] Signs and Symptoms of Untreated Lyme Disease, CDC, last reviewed: January 15, 2021. Retrieved from: https://www.cdc.gov/lyme/signs_symptoms/index.html [16] Photo credits: Alison Young, Taryn Holman, Yevgeniy Balagula/Dermatlas.org, Lyme Disease Rashes and Look-alikes, CDC, last reviewed: October 9, 2020. Retrieved from: https://www.cdc.gov/lyme/signs_symptoms/rashes.html [17] Photo Credit: Bernard Cohen/Dermatlas.org, Lyme Disease Rashes and Look-alikes, CDC, last reviewed: October 9, 2020. Retrieved from: https://www.cdc.gov/lyme/signs_symptoms/rashes.html [18] Moniuszko-Malinowska A, Czupryna P, Dunaj J, et al. Acrodermatitis chronica atrophicans: various faces of the late form of Lyme borreliosis. Postepy Dermatol Alergol. 2018;35(5):490-494. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232541/ [19] Photo credit, Glatz M et al., Clinical Spectrum of Skin Manifestations of Lyme Borreliosis in 204 Children in Austria, Advances in Dermatology and Venereology, Vol 95, Issue 5, Nov 4, 2014. Retrieved from: https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2000 [20] Warshafsky S et al., Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis, Journal of Antimicrobial Chemotherapy, Volume 65, Issue 6, June 2010, Pages 1137–1144. Retrieved from: https://academic.oup.com/jac/article-pdf/65/6/1137/2086677/dkq097.pdf [21] Nadelman R et al., Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite, N Engl J Med 2001; 345:79-84. Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJM200107123450201 [22] Photo Credit- Ticks Image Gallery, CDC, last reviewed: December 18, 2020. Retrieved from: https://www.cdc.gov/ticks/gallery/index.html [23] Smith G et al., Management of Tick Bites and Lyme Disease During Pregnancy, J Obstet Gynaecol Can 2012;34(11):1087–1091. Retrieved from: https://www.jogc.com/article/S1701-2163(16)35439-1/pdf [24] Treatment for erythema migrans, CDC, last reviewed: November 3, 2020. Retrieved from: https://www.cdc.gov/lyme/treatment/index.html [25] Post-Treatment Lyme Disease Syndrome, CDC, last reviewed: November 8, 2019. Retrieved from: https://www.cdc.gov/lyme/postlds/index.html [26] Ehrlichiosis Transmission, CDC,last reviewed: January 17, 2019. Retrieved from: https://www.cdc.gov/ehrlichiosis/transmission/index.html [27] Ehrlichiosis Epidemiology and Statistics, CDC, last reviewed: March 26, 2020. Retrieved from: https://www.cdc.gov/ehrlichiosis/stats/index.html [28] Ehrlichiosis Clinical and Laboratory Diagnosis, CDC, last reviewed: January 17, 2019. Retrieved from: https://www.cdc.gov/ehrlichiosis/healthcare-providers/diagnosis.html [29] Ehrlichiosis Signs and Symptoms, CDC, last reviewed: January 17, 2019. Retrieved from: https://www.cdc.gov/ehrlichiosis/healthcare-providers/diagnosis.html [30] Ehrlichiosis Treatment, CDC, last reviewed: January 17, 2019.Retrieved from: https://www.cdc.gov/ehrlichiosis/healthcare-providers/treatment.html initially published 2021.

A look at magnesium deficiency, supplementation, and toxicity. Culinary Medicine by Mary B Grosvenor, MS, RD and Lori A Smolin, PhD Contributor Stefanie Schwartz, MS, RD, CDN Magnesium, a mineral that has been recognized as a dietary essential since the 1920s, is currently “having a moment.”[1] It appeared in the Forbes list of nutrition and fitness trends and the “magnesium” hashtag has over a billion views on the social media platform TikTok. [2] It has long been known for a host of roles, including bone health and muscle and nerve function, but it is now also being promoted as a quick fix for problems ranging from anxiety and depression to sleep disorders.[3] Why has a nutrient that has been studied for a century emerged as a modern social media trend? The answer is more likely related to consumers’ interest in managing their own well-being and manufacturers’ interest in increasing supplement sales than to advances in our understanding of the role of magnesium in health. Functions of Magnesium About half of the magnesium in the body is in bone where it helps maintain structure. Magnesium is also found in cells and fluids throughout the body where it acts as a cofactor in numerous enzyme systems and is required for the synthesis of protein, DNA, and RNA.  Magnesium also forms a complex with ATP and is therefore needed in every reaction that uses or generates ATP. Magnesium plays a role in the active transport of calcium and potassium across cell membranes, which is important for nerve impulse conduction, muscle contraction, blood pressure regulation, and normal heart function.[4] Sources of Magnesium Magnesium is found in small amounts in a variety of foods (see photo). It is part of the structure of chlorophyll so is found in green vegetables. Legumes, nuts, peanut butter, seeds, and bananas are also good plant sources. Animal sources include milk, meat, poultry, and fatty fish, such as salmon.  Whole grains are a good source but refined grains, such as white bread, are poor sources because magnesium is contained in the bran and germ, which are removed during processing; a cup of whole-wheat flour contains six times the amount of magnesium found in a cup of white flour. Some foods such as breakfast cereals are fortified with magnesium. Water can also be a significant source. Certain laxatives and antacids contain magnesium, and it is available as a dietary supplement. Magnesium Intake and Health Despite the variety of food sources, dietary surveys suggest that as many as half of Americans consume less than the Recommended Dietary Allowance (RDA) for magnesium, which for adults over the age of 30 years is 420 mg for men and 350 mg for women.[4]  Early symptoms of magnesium deficiency include loss of appetite, nausea, and fatigue; if magnesium deficiency worsens, numbness, muscle cramps, seizures, abnormal heart rhythm, and personality changes can occur.[5] Symptomatic magnesium deficiency is uncommon in healthy people because the kidneys limit urinary excretion of this mineral when levels are low. However, subclinical deficiency can occur in individuals who typically consume insufficient amounts and in those with conditions that reduce absorption and/or increase excretion such as aging, gastrointestinal diseases, alcohol use disorder, and type 2 diabetes. [5]. Low magnesium intake is associated with an increased risk of several chronic diseases including osteoporosis, hypertension, heart disease, and type 2 diabetes.[5-8]  For example, a low intake of magnesium is correlated with lower bone mineral density and a higher risk of osteoporosis.[9] Adequate magnesium is needed to keep blood pressure in the normal range and magnesium deficiency is linked to high blood pressure. Higher intakes of magnesium are associated with a reduced risk of hypertension as well as heart disease and stroke.[5,10] With respect to diabetes, a meta-analysis found that magnesium levels in people with prediabetes are significantly lower than levels in healthy adults, suggesting that low magnesium may play a role in the development of prediabetes and its progression to diabetes.[11] Based on these correlations, it is not surprising that magnesium supplements have been investigated for their effectiveness in preventing and treating these chronic diseases. Magnesium supplementation has been found to benefit bone mineral density and fracture risk.[9] Some, but not all studies have found a reduction in blood pressure with magnesium supplements in individuals with and without hypertension.[12] Because studies of magnesium supplementation in cardiovascular disease  have used small sample sizes and varying types, doses, and durations of supplements it is difficult to determine if supplements provide a benefit.[13]  A few small studies have shown that magnesium supplements may improve glycemic control in Type 2 diabetes. [5,14] Are Magnesium Supplements Safe? The preferred way to increase nutrient intake is with food, which provides a variety of nutrients that collectively work together in maintaining health. However, there is little risk from consuming the Tolerable Upper Intake Level (UL) for magnesium of 350 mg/day from supplements and there is evidence this UL value, established in 1997, is set too low and that taking supplemental doses greater than 350 mg is safe.[15] For example, several of studies discussed here used magnesium supplements in doses that exceeded the UL with few side effects. The side effects for healthy adults, if they do occur, are generally limited to mild, reversible diarrhea. In fact, magnesium-based laxatives have been used for years as a treatment for constipation and there has been a recent resurgence in interest in the use of magnesium oxide as a safe, convenient, low cost treatment for chronic constipation. The recommendation is to start with 1000 mg taken in 3-4 doses throughout that day and if needed increase to up to 2000 mg/day. (See  Editor’s Note). Magnesium oxide is most effective as a laxative because it is poorly absorbed; it draws water into the intestine, which helps to promote bowel movements. Well-absorbed forms of magnesium supplements,  such as magnesium citrate, glycinate, orotate, and carbonate, are more effective in supporting the systemic roles of magnesium inside the body. [16] Even though magnesium supplements are generally safe, very large doses (more than 5,000 mg/day) from magnesium-containing laxatives and antacids have been associated with magnesium toxicity symptoms including hypotension, nausea, vomiting, lethargy, muscle weakness, irregular heartbeat, and, possibly, cardiac arrest. [5,16] Magnesium supplements of any dose should be used with caution by people with kidney disease because poor kidney function can limit excretion of excess magnesium. Magnesium supplements can also interact or interfere with certain medications. For example, supplements reduce the absorption of bisphosphonates, which are used to treat osteoporosis. Trending Roles for Magnesium Supplements If you acquire your nutrition recommendations from social media, you are likely to be taking a magnesium supplement to improve your mood, ease your stress, sleep better, or lessen leg cramps. Although social media is not a reliable source for health information, there is some promising scientific evidence for these benefits. Anxiety and Depression  A review of studies investigating the effects of magnesium supplements on anxiety found modest support for a beneficial effect with doses of up to 300 mg/day in individuals with mild to moderate levels of anxiety.[17]  A scientific review of magnesium and mental health found a correlation between low magnesium levels and depression and a beneficial effect of magnesium supplements on depression when taken alone or in combination with antidepressant medications. [18] For example, one study that provided 248 mg of supplemental magnesium for 6 weeks reported significant improvement in depression scores. [19] However, the review also suggests that more long-term, well-controlled studies are needed to definitively recommend supplementation for depression and anxiety. Stress  Stress triggers physiological and psychological responses in the body. In the short-term stress causes the release of adrenaline to increase heart rate and cortisol to increase blood sugar to help us escape from the perceived threat. When stress becomes chronic, it can worsen existing health problems and also cause or exacerbate anxiety and depression. Stress increases the release of magnesium into the blood stream and eventually causes magnesium loss as it is excreted by the kidneys. Low magnesium status is common in individuals suffering from psychological stress and this may be due in part to magnesium loss via the kidneys. Magnesium supplementation in the range of 300-400 mg/day has shown benefits in stressed but otherwise healthy subjects. [20] Sleep Disorders  Magnesium is a popular internet treatment for sleep disorders, including difficulty falling asleep and/or staying asleep.  Observational studies have shown low magnesium status in individuals with sleep disorders, particularly in older adults and those suffering from high levels of stress. [20]  Although currently there is not sufficient evidence from well-controlled clinical trials make to support the role of magnesium in sleep disorders, magnesium supplementation is a low cost, low risk option worth trying to improve sleep. [21,22] Muscle Cramps  A deficiency of magnesium can cause muscle twitching, cramping, and even seizures. However, in the absence of a deficiency, magnesium has not been shown to be effective at easing cramping. A review of magnesium supplementation of 100 to 520 mg/day found that it is unlikely that magnesium supplements provide a benefit in reducing leg cramps.[23] Migraines Although it is known that magnesium is important for energy homeostasis in the brain, the exact connection between magnesium and headaches has yet to be determined. A review of studies on headaches and magnesium suggests supplementation of 300 mg twice daily is a well-tolerated option in treating migraine and in enhancing the effects of typical antimigraine medications. [24] Conclusion The ability of social media to swiftly disseminate information may be promoting benefits of magnesium supplements more rapidly than the science can advance to back them up. The studies reviewed here do not provide adequate evidence based on well-designed research on magnesium supplementation to make specific recommendations. That said, in healthy adults there are many potential benefits and few risks associated with supplemental magnesium at doses less than 5000 mg. Editor’s note: Clinicians have started prescribing daily magnesium supplementation for chronic constipation.  The long term effects of this supplementation is not known. Although studies have shown that 1,000 mg of magnesium supplementation for chronic constipation is safe, consider starting with magnesium oxide 400 mg daily and titrating slowly upward.  Monitoring of serum magnesium levels may be warranted when using greater than this dosage.  Patients with renal disease or patients on digitalis may be at risk for hypermagnesemia. References: [1] Davis S. The Top Nutrition and Fitness Trends to Watch for in 2024, According to Experts. Forbes Health. Published December 6, 2023. https://www.forbes.com/health/wellness/top-nutrition-and-fitness-trends-2024/ [2] Love S. Magnesium is the latest buzzy supplement. Can it help with anxiety? The Guardian. https://www.theguardian.com/wellness/2024/jan/09/magnesium-tiktok-trend-anxiety-does-it-work. Published January 9, 2024. [3] Magnesium TikTok Health Hacks: Are the Benefits Real? Healthline. Published February 29, 2024. https://www.healthline.com/health-news/tiktoks-obsession-with-magnesium-healthy-or-hype [4] Institute of Medicine (IOM). Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride . Washington, DC: National Academy Press, 1997 [5] National Institutes of Health. Office of Dietary Supplements - Magnesium. National Institutes of Health. Published 2016. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ [6] Dickson HO, Nicolson D, Campbell F, et al. Magnesium supplementation for the management of primary hypertension in adults. Cochrane Database Syst Rev. 2006:CD004640. [7]  Joosten MM, Gansevoort RT, Mukamal KJ, et al. Urinary and plasma magnesium and risk of ischemic heart disease. Am J Clin Nutr. 2013;97:1299-1306. [8] Hruby A, O'Donnell CJ, McKeown NM. Magnesium Intake is inversely associated with coronary artery calcification. The Framingham Heart Study. JACC Cardiovasc Imaging. 2014;7:59-69. [9] Rondanelli M, Faliva MA, Tartara A, et al. An update on magnesium and bone health. BioMetals. 2021;34(4). doi:https://doi.org/10.1007/s10534-021-00305-0 [10] Rosique-Esteban N, Guasch-Ferré M, Hernández-Alonso P, Salas-Salvadó J. Dietary Magnesium and Cardiovascular Disease: a Review with Emphasis in Epidemiological Studies. Nutrients. 2018;10(2):168. doi:https://doi.org/10.3390/nu10020168 [11] Ebrahimi Mousavi S, Ghoreishy SM, Hemmati A, Mohammadi H. Association between magnesium concentrations and prediabetes: a systematic review and meta-analysis. Scientific Reports. 2021;11(1). doi:https://doi.org/10.1038/s41598-021-03915-3 [12] Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015;7(9):8199-8226. doi:https://doi.org/10.3390/nu7095388 [13] Fritzen R, Davies A, Veenhuizen M, et al. Magnesium Deficiency and Cardiometabolic Disease. 2023;15(10):2355-2355. doi:https://doi.org/10.3390/nu15102355 [14] ELDerawi W, Naser I, Taleb M, Abutair A. The Effects of Oral Magnesium Supplementation on Glycemic Response among Type 2 Diabetes Patients. Nutrients. 2018;11(1):44. doi:https://doi.org/10.3390/nu11010044 [15] Costello R, Rosanoff A, Nielsen F, West C. Perspective: Call for Re-evaluation of the Tolerable Upper Intake Level for Magnesium Supplementation in Adults. Advances in Nutrition. Published online July 22, 2023. doi:https://doi.org/10.1016/j.advnut.2023.06.008 [16] Mori H, Tack J, Suzuki H. Magnesium Oxide in Constipation. Nutrients. 2021 Jan 28;13(2):421. doi:https://doi: 10.3390/nu13020421. [17] Boyle N, Lawton C, Dye L. The Effects of Magnesium Supplementation on Subjective Anxiety and Stress—A Systematic Review. Nutrients. 2017;9(5):429. doi:https://doi.org/10.3390/nu9050429 [18] Botturi A, Ciappolino V, Delvecchio G, Boscutti A, Viscardi B, Brambilla P. The Role and the Effect of Magnesium in Mental Disorders: A Systematic Review. Nutrients. 2020;12(6):1661. doi:https://doi.org/10.3390/nu12061661 [19] Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. Song Y, ed. PLOS ONE. 2017;12(6):e0180067. doi:https://doi.org/10.1371/journal.pone.0180067 [20] Pickering G, Mazur A, Trousselard M, et al. Magnesium status and stress: The vicious circle concept revisited. Nutrients. 2020;12(12):3672. doi:https://doi.org/10.3390/nu12123672 [21] Arab A, Rafie N, Amani R, Shirani F. The role of magnesium in sleep health: A systematic review of available literature. Biological Trace Element Research. 2022;201(1). doi:https://doi.org/10.1007/s12011-022-03162-1 [22] Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis. BMC Complementary Medicine and Therapies. 2021;21(1). doi:https://doi.org/10.1186/s12906-021-03297-z [23] Moretti A. What is the role of magnesium for skeletal muscle cramps? A Cochrane Review summary with commentary. Journal of Musculoskeletal & Neuronal Interactions. 2021;21(1):1-3 [24] Domitrz I, Cegielska J. Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine-From Theory to Practice. Nutrients. 2022;14(5):1089. Published 2022 Mar 5. doi:10.3390/nu14051089

A Springtime Superfood: Unveiling the Health Benefits and Culinary Versatility of Asparagus Asparagus isn't just a delicious spring herald, it's a nutritional powerhouse. Packed with fiber, vitamins, and boasting prebiotics for gut health, asparagus is a friend to your digestive system. This versatile veggie can be enjoyed simply roasted or dressed up in a fancy dish, making it a perfect addition to any meal. Plus, learn the fascinating history and folklore surrounding this "vampire of the vegetable world." Culinary Medicine by Mary B Grosvenor, MS, RD and Lori A Smolin, PhD Spring has sprung or at least the asparagus has. Asparagus is usually the first vegetable ready for harvest, popping its stalks up as early as March. It’s early because unlike most other vegetables that must be planted every year, asparagus is a perennial that sends up tender stalks from early spring until the end of June for 15 to 20 years! So, while you are waiting to even plant other garden vegetables like tomatoes and beans, enjoy some fresh asparagus. Asparagus is native to Europe, North Africa, and Asia, where it grew wild along riverbanks and coastal areas in sandy, salty soil. Cultivation began more than 2,000 years ago and it was prized by the Greeks and Romans for its flavor, texture, and medicinal properties.[1] Colonists are believed to have brought asparagus to North America in the 1700s, planting it initially in New England.[2] Wild asparagus can still be found growing in ditches and beach areas across the United States. It is recognizable because the uncut asparagus spears grow and branch into fern-like plants with yellow flowers and red berries that appear in the fall. Today Michigan, California, and Washington are the leaders in US asparagus production, but most of the 500 million pounds of asparagus Americans consume each year is imported from Mexico and Peru.[3] Asparagus spears are harvested when they are about 6 to 10 inches tall. The spears can be thick or thin and green, white, or purple. The thickness of the asparagus spear is an indication of the plant’s age; they are thick or thin from the moment they sprout. Most asparagus is green.  Although white asparagus spears are more tender than green, they come from the same plant but are picked before they poke their heads out into the sun.[4] As a result, white asparagus never develops chlorophyll, which gives the green color to green asparagus. Since it spends its life in the dark, white asparagus has been called the vampire of the vegetable world.[5] The purple variety, developed in Italy, is sought after for its milder, slightly sweeter flavor. Unfortunately, most of the purple color disappears when it is cooked. While asparagus doesn’t have specific medicinal or vampire-like properties, it is packed with nutrition. It is rich in fiber, vitamin K, and folate and is a source of B vitamins and vitamins A, E, C as well as iron and zinc. Asparagus is low in calories and sodium and for a green vegetable, high in protein, with 3 grams in a cup. The fiber in asparagus is rich in prebiotic fructooligosaccharides, which make their way to the colon where they are a food source for intestinal bacteria and thus promote the growth and maintenance of healthy microbiota.[6] There are slight nutritional differences between various colors of asparagus. The purple variety is higher in sugar and lower in fiber than green and white asparagus. But purple asparagus also has higher levels of anthocyanins, antioxidant phytochemicals that have anti-inflammatory and anti-cancer properties. [7] Despite asparagus’s nutritional clout, many may pass up this delicacy because it tends to be more expensive than other vegetables. This is mainly because it is difficult to harvest; each spear must be hand cut and it can’t be overharvested because the plant needs to maintain energy to send up spears the next year. Another reason some may shy away from asparagus is that it gives urine a distinctive smell. This odor comes from a compound called asparagusic acid, which the body converts into a group of volatile sulfur-containing compounds that appear in the urine as soon as soon as 15 to 30 minutes after eating. These compounds have an unpleasant smell but are harmless. Curiously, because of genetic variations, not everyone produces or can smell the odor.[8] So, add some elegance along with nutrition to your meals. Asparagus makes a classy appetizer. It can be a simple vegetable boiled or roasted and then drizzled with olive oil and lemon juice, or you can dress it up with hollandaise sauce. It is a delicious addition to a casserole.  And leftovers can be tossed into your salad or grain dishes. Get this great Salmon, Asparagus, and Rainbow Potatoes Recipe References [1] Asparagus, Considered a Delicacy Since Ancient Times. Asparagus, Considered a Delicacy Since Ancient Times. Accessed April 10, 2024. https://www.uaex.uada.edu/counties/miller/news/fcs/fruits-veggies/asparagus.aspx#:~:text=The%20Greeks%20believed%20asparagus%20was [2] A History of Asparagus back to Roman Times. www.asparagus-lover.com. https://www.asparagus-lover.com/history-of-asparagus.html ‌ [3] Happy National Asparagus Day! Get to Know Spring’s Delicious Vegetable | USDA. www.usda.gov. https://www.usda.gov/media/blog/2022/05/24/happy-national-asparagus-day-get-know-springs-delicious-vegetable#:~:text=While%20domestic%20production%20continues%20to [4] Organics B. Everything You Never Knew About Asparagus. blog.bostonorganics.com. https://blog.bostonorganics.com/everything-you-never-knew-about-asparagus ‌ [5] White Asparagus: The Vampire Of The Vegetable World. HuffPost. Published April 10, 2012. https://www.huffpost.com/entry/white-asparagus_n_1412329 ‌ [6] Redondo-Cuenca A, García-Alonso A, Rodríguez-Arcos R, et al. Nutritional composition of green asparagus (Asparagus officinalis L.), edible part and by-products, and assessment of their effect on the growth of human gut-associated bacteria. Food Research International (Ottawa, Ont). 2023;163:112284. doi:https://doi.org/10.1016/j.foodres.2022.112284 ‌[7] The History of Asparagus. kitchenproject.com. https://kitchenproject.com/history/Asparagus/index.htm [8] Pelchat ML, Bykowski C, Duke FF, Reed DR. Excretion and perception of a characteristic odor in urine after asparagus ingestion: a psychophysical and genetic study. Chem Senses. 2011;36(1):9-17. https://doi:10.1093/chemse/bjq081

References for CME Article " Communication Issues in Healthcare, Its Relation to Malpractice Risk, and How to Communicate More Effectively " References [1] Malpractice Risks in Communication Failures, 2015 Annual Benchmarking report.  Crico.  2015. https://www.candello.com/Insights/Candello-Reports/Communications-Report [2] Communicating Clearly and Effectively to Patients. Joint Commission International. 2018. Retrieved from: https://store.jointcommissioninternational.org/assets/3/7/jci-wp-communicating-clearly-final_(1).pdf [3]Solet, Darrell Jet al. Lost in Translation: Challenges and Opportunities in Physician-to-Physician Communication During Patient Handoffs. Academic Medicine 80(12):p 1094-1099, December 2005. Retrieved from: https://journals.lww.com/academicmedicine/fulltext/2005/12000/lost_in_translation__challenges_and_opportunities.5.aspx [4] Kitch BT et al. Handoffs causing patient harm: a survey of medical and surgical house staff. Joint Commission Journal of Quality and Patient Safety, October 2008; 34(10):563-70. Retrieved from: https://www.sciencedirect.com/science/article/abs/pii/S1553725008340719?via%3Dihub [5] Lester GW, and Smith SG. Listening and Talking to Patients A Remedy for Malpractice Suits? West J Med 1993 Mar; 158:268-272. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1311752/pdf/westjmed00079-0050.pdf [6] Beckman HB and Frankel RM. The Effect of Physician Behavior on the Collection of Data. Ann Intern Med.1984;101:692-696. Retrieved from: https://www.researchgate.net/publication/16708907_The_effect_of_physician_behavior_on_collection_of_date [7] Rhodes KV, Vieth T, He T, et al. Resuscitating the physician-patient relationship: emergency department communication in an academic medical center. Ann Emerg Med. 2004;44(3):262-267. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/15332069/ [8] Burack RC, Carpenter RR. The predictive value of the presenting complaint. J Fam Pract. 1983;16:749-54. Retrieved from: https://cdn.mdedge.com/files/s3fs-public/jfp-archived-issues/1983-volume_16-17/JFP_1983-04_v16_i4_the-predictive-value-of-the-presenting-c.pdf [9] Waitzkin H. Doctor-Patient Communication: Clinical Implications of Social Scientific Research. JAMA. 1984;252(17):2441–2446. Retrieved from: https://jamanetwork.com/journals/jama/article-abstract/395047 [10] Thompdon J. Is Nonverbal Communication a Numbers Game? Psychology Today. September 30, 2011. Retrieved from:  https://www.psychologytoday.com/us/blog/beyond-words/201109/is-nonverbal-communication-a-numbers-game [11] DiMatteo MR, Taranta A, Friedman HS, Prince LM. Predicting patient satisfaction from physicians' nonverbal communication skills. Med Care. 1980;18(4):376-387. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/7401698/ [12] Schmid Mast M. On the importance of nonverbal communication in the physician–patient interaction. Patient Education and Counseling.  Volume 67, Issue 3, 2007, Pages 315-318. Retrieved from: https://www.sciencedirect.com/science/article/abs/pii/S0738399107000973?via%3Dihub [13] Nalini Ambady n et al. Surgeons' tone of voice: A clue to malpractice history. Surgery. Volume 132, Issue 1, 2002, Pages 5-9. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/12110787/ [14] J.A. Hall JA et al. Nonverbal behavior in clinician-patient interaction. Appl Prev Psychol, 4 (1995), pp. 21-37. Retrieved from: https://www.researchgate.net/publication/222501767_Nonverbal_behavior_in_clinician-patient_interaction [15] Stewart MA. Effective physician-patient communication and health outcomes: a review. CMAJ. 1995;152(9):1423-1433. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1337906/pdf/cmaj00069-0061.pdf [16] Kaplan SH, Greenfield S, Ware JE Jr. Assessing the effects of physician-patient interactions on the outcomes of chronic disease [published correction appears in Med Care 1989 Jul;27(7):679]. Med Care. 1989;27(3 Suppl):S110-S127. Retrieved from: file:///C:/Users/stuar/Downloads/assessing_the_effects_of_physician_patient.10.pdf [17] Laws MB et al. Factors associated with patient recall of key information in ambulatory specialty care visits: Results of an innovative methodology. PLoS ONE 13(2): e0191940. Retrieved from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191940#sec013 [18] Talevski J, Wong Shee A, Rasmussen B, Kemp G, Beauchamp A. Teach-back: A systematic review of implementation and impacts. PLoS One. 2020;15(4):e0231350. Published 2020 Apr 14. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156054/ [19] Yen PH, Leasure AR. Use and Effectiveness of the Teach-Back Method in Patient Education and Health Outcomes. Fed Pract . 2019;36(6):284-289. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590951/ [20] Samuels-Kalow M, Hardy E, Rhodes K, Mollen C. "Like a dialogue": Teach-back in the emergency department. Patient Educ Couns . 2016;99(4):549-554. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808368/ [21] Gotlieb R, Praska C, Hendrickson MA, et al. Accuracy in Patient Understanding of Common Medical Phrases. JAMA Netw Open. 2022;5(11):e2242972. Retrieved from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799079 [22] Keller Vf , Carroll JG. A new model for physician-patient communication. Patient Education and Counseling 23 (1994) 131-140. Retrieved from: https://www.sciencedirect.com/science/article/abs/pii/0738399194900515 [23] Street RL. Information-giving in medical consultations: The influence of patients' communicative styles and personal characteristics. Social Science & Medicine. Volume 32, Issue 5,1991, Pages 541-548. Retrieved from: https://www.sciencedirect.com/science/article/abs/pii/027795369190288N [24] Korsch BM, Gozzi EK, Francis V. Gaps in doctor-patient communication. 1. Doctor-patient interaction and patient satisfaction. Pediatrics. 1968;42(5):855-871. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/5685370/ for CME article " Communication Issues in Healthcare, Its Relation to Malpractice Risk, and How to Communicate More Effectively "

The world of salt – once a prized commodity for preserving food, now a ubiquitous seasoning with a complex array of varieties and claims. Discover the truth behind artisanal salts and their impact on health and culinary experiences. Culinary Medicine by Mary B Grosvenor, MS, RD and Lori A Smolin, PhD Salt… To the ancients, it was a rare commodity used to preserve food. Trade routes carried salt through Europe, Asia, and Northern Africa; it was so valuable that it was taxed, fought over, and traded ounce for ounce for gold. Salt was also revered for medicinal as well as mystical properties. [1] In the modern world, salt is desired primarily for its ability to enhance the flavor of food; it is the most popular seasoning in the world.[1,2] No longer rare, salt is mined, pulverized, iodized, and even demonized due to its connection to high blood pressure. Despite the potential ill health effects of salt, a growing market of artisanal varieties entice us with their exotic names and colors and claims of health promoting properties.[2] But are they really any different than plain old table salt? Salt, a crystalline compound made up of the minerals sodium and chloride, comes from two main sources: mines and sea water. Salt from underground mines is in the form of halite, also known as rock salt. The halite is processed to remove other minerals and crushed to achieve the fine texture of what we call table salt.[3,4] Himalayan salt is also harvested from mines, but it not processed and refined like table salt. It contains small amounts of additional minerals including iron, which contributes to its various hues. Salt from sea water is produced by evaporation.  This sea salt is less processed than table salt and retains traces of other minerals, such as magnesium, potassium, and calcium, which provide flavor and color to the salt.  Some salt, whether from a mine or the sea, also contains additives. Calcium silicate is often added to prevent clumping and iodine may be added to help prevent iodine deficiency. The addition of iodine to salt began in the United States in the 1920s; currently 88% of the world’s population uses iodized salt.[5,6] The sodium and chloride in salt are both dietary essentials.  In the body they help regulate fluid and acid-base balance and are needed for nerve conduction and muscle contraction. However, too much sodium in the diet can contribute to high blood pressure; as sodium intake goes up so does blood pressure. High blood pressure over time can lead to heart failure, heart attack, and stroke.[7] The recommended sodium intake for most adults is no more than 2,300 mg a day with an ideal limit of 1,500 mg per day.[8]  However, many of us consume more than this and as a result public health campaigns are underway to promote a reduction in sodium intake.[7] In response to recommendations to reduce sodium intake, many Americans have switched to specialty salts such as pink Himalayan salt and sea salt thinking they are a healthier alternative. In a survey by the American Heart Association, 61% of respondents thought that sea salt was a lower sodium alternative to table salt. Others are choosing these salts because they are less processed and contain additional nutrients. [9] Unfortunately, Himalayan salt and sea salt have just as much sodium as table salt. They do have additional essential minerals, but the amounts are insignificant nutritionally. The claims on the healthfulness of these salts, such as reducing muscle cramping and maintaining normal pH balance, are also true of any form of salt. Although specialty salts are not different nutritionally, they do add different qualities to food. The minerals in some salts give them distinct colors and flavors. For example, Himalayan pink salt is chosen for its attractive color. Volcanic black salt, whether from Hawaii or the Himalayas, is high in sulfur giving it an egg-like flavor; it is often used in Indian and vegan dishes. The size of the salt grain affects both taste and texture. Larger, coarser salt granules or flakes such as Kosher salt and Flake salt offer a burst of flavor and a crunchier texture. They are best sprinkled on foods just before or immediately after cooking. Small grains of salt, what we typically think of as table salt, dissolve quickly, distribute evenly, and do not add any crunch. While some salts can be used interchangeably in recipes, choosing a small grain salt for baking is important.  The small grains pack tightly in a measuring spoon, so if you replace a teaspoon of table salt with a teaspoon of coarser Kosher salt you will actually be adding less salt to your cookies. Which salt you choose depends on your personal preferences for taste and appearance as well as what works best in your recipe. Nutritionally there are only minute differences in the amounts of sodium and other minerals in different types of salt. Public health guidelines suggest we keep our intake within recommend limits, so pick salts you enjoy and use them in moderation. Despite advertising, none have mystical powers, though the right crunch or color can transform your recipe. References [1] Roberts WC, Roberts WC. Facts and Ideas from Anywhere. Baylor University Medical Center Proceedings. 2001;14(3):314-322. doi:https://doi.org/10.1080/08998280.2001.11927784 ‌[2] DiNicola C. Everything You Need To Know About Salt. Tasting Table. Published January 26, 2023. https://www.tastingtable.com/1179418/everything-you-need-to-know-about-salt/#:~:text=It%27s%20universally%20loved%20and%20heavily [3] Salt Production and Processing. Morton Salt. https://www.mortonsalt.com/article/salt-production-processing [4] Zeratsky K. Sea salt vs. table salt: What’s the difference? Mayo Clinic. Published 2016. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/sea-salt/faq-20058512 [5] Office of Dietary Supplements - Iodine. ods.od.nih.gov. Accessed March 13, 2024. https://ods.od.nih.gov/factsheets/Iodine-HealthProfessional/#:~:text=Overall%2C%20it%20appears%20that%20the [6] Zimmermann MB, Andersson M. GLOBAL ENDOCRINOLOGY: Global perspectives in endocrinology: coverage of iodized salt programs and iodine status in 2020. European Journal of Endocrinology. 2021;185(1):R13-R21. doi:https://doi.org/10.1530/eje-21-0171 ‌[7] Harvard T.H. Chan. Salt and Sodium. The Nutrition Source. Published July 18, 2013. https://www.hsph.harvard.edu/nutritionsource/salt-and-sodium/#:~:text=The%20human%20body%20requires%20a ‌[8] National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Food and Nutrition Board; Committee to Review the Dietary Reference Intakes for Sodium and Potassium; Oria M, Harrison M, Stallings VA, editors. Dietary Reference Intakes for Sodium and Potassium. Washington (DC): National Academies Press (US); Summary. National Academies Press (US); 2019. https://www.ncbi.nlm.nih.gov/books/NBK545430/ ‌[9] Sea Salt vs. Table Salt. www.heart.org. https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/sodium/sea-salt-vs-table-salt#:~:text=In%20a%20survey%20conducted%20by

While whole foods reign supreme, who has time to cook everything from scratch? Smartly chosen processed foods can add variety, nutrients & safety to your diet. Culinary Medicine By Lori A Smolin, PhD and Mary B Grosvenor, MS, RD “Eat more whole foods. Avoid processed foods.” We hear this all the time. It makes sense that whole foods, such as peaches plucked directly from the tree, are healthy choices. Donuts and chips on the other hand are processed foods; while we enjoy these, we also know they aren't the healthiest option. But these sugary and salty snacks are not the only processed foods in our diets. According to the U.S. Department of Agriculture processed foods include any food that has been changed from its natural state.[1] So, food that has been cleaned, chopped, canned, cooked, frozen, or altered in any way is considered processed. According to this definition, a bowl of oatmeal, a cup of frozen broccoli or fresh chopped spinach, and even a fresh peach, if you wash it, are considered processed. Clearly, all processed foods are not unhealthy but understanding which processed foods should be limited in your diet can be confusing. The Spectrum of Processed Foods “Processed” is a very broad category in the world of food.  Some forms of processing are beneficial; they make food safer, less perishable, more convenient, or more nutrient dense. For example, washing removes pesticides from fruit so we don’t ingest them. Canning or freezing vegetables allows us to have green beans in January because they can be stored for extended periods without spoiling. And, as anyone who has ever emptied a packaged salad mix into their bowl will attest, processed foods can make it more convenient to add a salad to your meal. Processing can also add nutrients to food: Milk has added vitamin D, a nutrient that’s low in our diets, and refined grain products such as white rice and white bread have added folic acid, which helps prevent birth defects. If we eliminate these processed foods, we could reduce the variety and nutrient content of our diets. But not all processing has our health and safety in mind. Some processing is used to make products more tempting, so we eat more, and manufacturers sell more.  These highly- or ultra-processed foods contain many additives such as flavors, colorings, and preservatives. They are formulated by separating, grinding, spinning, extruding, heating, and/or cooling ingredients extracted from whole foods.[2] The extensive processing that makes these foods convenient also causes the loss of nutrients such as fiber, vitamins, and minerals. And, to enhance flavor, these foods typically have added salt, saturated fat, and/or sugars, nutrients that should be limited in a healthy diet. For example, turning a potato into potato chips creates a tasty snack, but also adds a lot of salt. Making fish into fish sticks, triples the saturated fat. A bottle of sweet tea is refreshing and easy to grab from the corner store but contains 42 grams of added sugar; more than three quarters of the amount recommended for an entire day. Ultra-Processed Foods, Nutrient Intake, and Health It is estimated that 73% of the American food supply is made up of ultra-processed foods; reliance on these foods affects our nutrient intake and health.[3,4] The consumption of ultra-processed food is associated with lower overall diet quality as indicated by an increase in the consumption of saturated fat, salt, and added sugars, and a decrease in fiber, protein, unsaturated fat, minerals (potassium, zinc, iron, and magnesium), vitamins (including vitamins A, C, D, E, B12, and niacin), and phytochemicals.[5] In addition, consuming more ultra-processed food increases our calorie intake. A study that examined the impact of ultra-processed foods on intake found that people consume more calories when offered a diet high in ultra-processed foods.[6] This is not surprising because the salt and sugar added to these products makes them very appealing to our taste buds. Diets high in ultra-processed foods are associated with an increased risk of obesity, cardiovascular disease, high blood pressure, type 2 diabetes, cancer, gastrointestinal disease, depression, and frailty, as well as all-cause mortality.[7,8] No study has reported an association between ultra-processed foods and beneficial health outcomes. A Healthy Dietary Pattern and Ultra-processed Foods A healthy dietary pattern can include some ultra-processed foods as long as the pattern is built on a base of healthy whole and minimally processed foods like fresh fruits and vegetables, whole grains, legumes, nuts, milk, and fresh meats and fish. The first step in planning your intake of ultra-processed foods is to recognize the foods that fall into this category. Ultra-processed foods generally do not resemble their original food source; cheese puffs do not look like corn or cheese. These foods often contain more than 5 ingredients and include additives and other ingredients you rarely find in your home kitchen and may not want in your diet. For example, your peanut butter may contain unhealthy hydrogenated vegetable oil. You can find all of the ingredients in a food, including added colors, flavor enhancers, preservatives, emulsifiers, and thickeners, on the ingredient list in order of prominence by weight. You can then evaluate the nutritional contribution of  your ultra-processed foods. Some, such as soda and candy, provide little in the way of nutrition besides calories, while others enhance your nutrient intake. Fortified plain soymilk, for example, fits into the ultra-processed category but is high in protein, calcium, and vitamins A, B12, and D and low in salt, saturated fat, and added sugars. Once you can recognize ultra-processed foods, consider why you may want them in your diet; personal preferences, cooking abilities, and the amount of time and money available for preparation also influence food purchases. For example, you may choose a jar of pasta sauce rather than expending the time and effort required to buy fresh tomatoes, onions, and garlic to make your own sauce. We buy packaged vegetables, soups, cereals, and even frozen dinners because they make food preparation easier, quicker, and more convenient. These ultra-processed foods make important nutritional contributions to our diet but still allow us to prepare a quick meal when we are pressed for time. For example, fortified breakfast cereal is a fast easy breakfast when you are in a hurry in the morning. Compared with grabbing a donut on the way to work, it supplies a host of vitamins and minerals, provides fiber if it is made with whole grains, and if you add milk, your breakfast is a good source of calcium. If you are tired and hungry at the end of the workday, pulling a pre-cooked dinner out of the freezer can provide a healthier, less expensive meal than stopping for fast food on the way home. On the other hand, ultra-processed snacks and desserts, such as chips and cookies, have few nutritional pluses but we choose them because we enjoy them.  No one food can make or break your diet nutritionally so including reasonable amounts of these treats occasionally is unlikely to have a significant impact on the overall healthfulness of your diet (see Figure). Summary While it may be healthiest to consume a diet of whole, minimally processed foods, the time, money, cooking facilities, and culinary skill required to purchase and prepare all your food from scratch make this close to impossible. Avoiding all processed foods not only makes the diet more difficult to acquire and prepare but also potentially less varied, less nutritious, and less safe. On the other hand, choosing a diet based on ultra- processed foods, is fast and easy but not good for your nutrition or health. The goal is to choose the best of both worlds. Base your diet on the freshness and purity of whole and minimally processed foods and supplement these with the convenience and variety provided by some ultra-processed choices (see Figure). #CulinaryMedicine References [1] Weaver CM, Dwyer J, Fulgoni VL, et al. Processed foods: contributions to nutrition. The American Journal of Clinical Nutrition. 2014;99(6):1525-1542. doi:https://doi.org/10.3945/ajcn.114.089284 [2] Monteiro. Ultra-Processed Foods, Diet Quality, and Health Using the NOVA Classification System. Rome, FAO. FAO; 2019. [3] Menichetti G, Ravandi B, Mozaffarian D, Barabási AL. Machine learning prediction of the degree of food processing. Nature Communications. 2023;14(1):2312. doi:https://doi.org/10.1038/s41467-023-37457-1 [4] Monteiro CA, Cannon G, Levy RB, et al. Ultra-processed foods: what they are and how to identify them. Public Health Nutr. 2019;22(5):936-941. doi:10.1017/S1368980018003762 [5] Zhang Y, Giovannucci EL. Ultra-processed foods and health: a comprehensive review. Critical Reviews in Food Science and Nutrition. Published online June 6, 2022:1-13. doi:https://doi.org/10.1080/10408398.2022.2084359 [6] Hall KD, Ayuketah A, Brychta R, et al. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metabolism. 2019;30(1). doi:https://doi.org/10.1016/j.cmet.2019.05.008 [7] Elizabeth L, Machado P, Zinöcker M, Baker P, Lawrence M. Ultra-Processed Foods and Health Outcomes: A Narrative Review. Nutrients. 2020;12(7):1955. doi:https://doi.org/10.3390/nu12071955 [8] Cordova R, Kliemann N, Huybrechts I, et al. Consumption of ultra-processed foods associated with weight gain and obesity in adults: A multi-national cohort study. Clinical Nutrition. 2021;40(9):5079-5088. doi:https://doi.org/10.1016/j.clnu.2021.08.009

Normal red blood cells have a life span of about 120 days which is shortened when hemolysis occurs. Review the different types of hemolytic anemia. InBrief by Stuart M Caplen, MD There are numerous causes of hemolytic anemia which is caused by hemolysis, the destruction of red blood cells. Normal RBCs have a life span of about 120 days which is shortened when hemolysis occurs. Red Blood Cell Abnormalities Hemolysis can be caused by abnormalities in the red blood cell (RBC). It can occur with a hemoglobinopathy when hemoglobin is altered. A membranopathy is where the structure of the red cell membrane may be changed, and the red cell becomes less deformable. In both hemoglobinopathies and membranopathies RBCs may not be flexible enough to pass through the spleen where they are typically sequestered and phagocytized. An enzymopathy, a process which adversely affects an RBC’s metabolic processes, can also cause hemolysis.[1] Examples of hemoglobinopathies leading to hemolysis include thalassemia and sickle cell disease. Diseases of red cell membranes (membranopathies) include hereditary spherocytosis and hereditary elliptocytosis. RBC enzymopathies include glucose-6-phosphate dehydrogenase deficiency (G6PD) and pyruvate kinase deficiency.[1] G6PD is an example of oxidative hemolysis. This is where the patient when exposed to certain medications or substances converts reduced state ferrous (2+) iron in hemoglobin, which carries oxygen, to the oxidized ferric (3+) iron, or methemoglobin which does not.[2] This results in methemoglobinemia where the hemoglobin molecule is unable to effectively carry oxygen. The ferric iron is denatured by the body and turns into what are known as Heinz bodies. G6PD is an X chromosome recessive disorder seen mostly in men of Mediterranean and African descent. While methylene blue is used to treat methemoglobinemia from other causes it can worsen G6PD patients and care is supportive and avoiding the offending substance that caused the problem. There is a substantial list of substances that can precipitate oxidative hemolysis in G6PD patients.[3] G6PD is also known as favism due to the fava bean being a common inciting food. A full list of substances to be avoided in G6PD patients can be found at this hyperlink: https://www.g6pd.org/en/G6PDDeficiency/SafeUnsafe/DaEvitare_ISS-it Other Causes of Hemolysis Factors external to the RBC also can cause hemolysis and include mechanical destruction, immune-mediated hemolysis, drug-induced, envenomations and infectious causes. RBC blood transfusions can cause both acute and delayed hemolytic reactions. Mechanical trauma to RBCs causing hemolysis as can be seen in march hemoglobinuria and with malfunctioning prosthetic cardiac valves. Malaria and babesiosis infections are known to destroy RBC’s. Certain snake bites may cause hemolysis. Paroxysmal nocturnal hemoglobinuria may also result in hemolysis. RBC fragmentation from thrombotic microangiopathy leading to microangiopathic hemolytic anemia can occur with thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, hemolytic uremic syndrome and the HELLP syndrome in pregnancy (hemolysis, elevated liver enzymes and low platelets).[1] They are all classified as thrombotic microangiopathies, where RBCs are mechanically damaged as they as they pass through small blood vessels that have endothelial damage, microthromboses, platelet aggregations and fibrin deposits.[6,7,8,9] There are over 150 drugs that have been documented to potentially cause hemolytic anemia. The most common are penicillins, cephalosporins, methyldopa, β-lactamase inhibitors such as clavulanate, nonsteroidal anti-inflammatory drugs and quinidine.[1,3,4,5] Drugs can cause hemolysis either by an immune mechanism or by a direct toxic effect.[10] In the newborn, onset of hyperbilirubinemia or anemia may be from hemolysis. Hemolytic disease of the newborn is caused by maternal antibodies that lead to destruction of RBCs in the infant. G6PD disease should also be considered as a possible cause of hemolysis in infants.[3] History and Physical Exam A careful history should be taken to try to limit diagnostic possibilities as there are so many different etiologies of hemolysis. The physical exam, depending on the acuity may reveal pallor, jaundice, hematuria, shortness of breath, weakness, fatigue, tachycardia, congestive heart failure if the anemia is severe, or the physical exam may be normal. Specific physical findings will depend on the etiology of the hemolysis. Laboratory tests Lactate dehydrogenase (LDH) is found inside RBCs, and when they rupture LDH levels typically increase. Haptoglobin binds to free hemoglobin. As RBCs lyse and hemoglobin is released there will be decreased levels of haptoglobin. There typically is an elevated reticulocyte count, as the bone marrow attempts to produce increased amounts of RBCs. A complete blood count will typically reveal a normocytic anemia. There may be hemoglobinuria. Indirect bilirubin (unconjugated bilirubin) may be elevated from breakdown of hemoglobin porphyrin.[1] Autoimmune hemolytic anemia is caused by autoantibody-mediated destruction of RBCs. Autoimmune hemolysis can be idiopathic, from viral or bacterial infections, autoimmune diseases, connective tissue disorders, lymphoproliferative cancers, blood transfusions, or organ transplants.[3] Autoimmune hemolysis typically causes a positive direct antiglobulin test (DAT) or Coombs test. Depending on the binding temperature, autoimmune hemolysis is subdivided into cold and warm agglutinin types. Warm is more commonly seen than cold and involves immunoglobulin G (IgG) antibodies, typically to the Rh complex, that react with the RBC membrane at normal body temperatures. Cold agglutinins are due to IgM antibodies that react with antigens on the surface of an RBC at low temperatures and can cause RBC lysis by complement fixation. Cold agglutinins may cause more symptoms in cold climates or in the extremities where body temperature is lower. About half of patients with cold agglutination disease will have acrocyanosis or Raynaud’s phenomenon.[4] Mycoplasma pneumonia and mononucleosis are two diseases that can commonly may cause cold agglutinin hemolysis.[3] Blood Smear Examination A blood smear can help differentiate the etiology of the hemolysis. Specific findings to look for include spherocytes, elliptocytes, fragmented red cells such as helmet cells or schistocytes, intercellular Babesia or malaria organisms, sickled cells, bite cells (also known as blister cells) and inclusions called Heinz bodies, which are particles of denatured hemoglobin. Bite cells occur when the Heinz bodies are removed by the spleen.[1] Spherocytes can be seen in hereditary spherocytosis as well as autoimmune and drug induced hemolytic anemia. Elliptocytes indicate hereditary elliptocytosis. When RBCs fragment from direct trauma, such as in march hemoglobinuria and malfunctioning prosthetic cardiac valves, a macroangiopathic hemolytic anemia may result and schistocytes may be seen. Some schistocytes may be seen after recent extracorporeal membrane oxygenation (ECMO) or coronary bypass surgery. Thrombotic microangiopathy can also produce schistocytes and microangiopathic hemolytic anemia in diseases such as the HELLP syndrome, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and drug induced hemolytic anemia. Schistocytes may also be seen in infections such as rickettsia, malaria or HIV. Bite cells and Heinz bodies, although they may be seen in some toxin exposures and with some oxidizing drugs, are more typically seen in G6PD.[3,11] Treatment Treatment of hemolysis and hemolytic anemia depends on the cause and may include blood transfusions, splenectomy, immunosuppressants, erythropoiesis-stimulating agents, bone marrow transplants, CRISPR gene therapy, stopping of an offending medication, or cardiac valve replacement. Since there are so many different etiologies, a full discussion of treatment is beyond the scope of this article.[1,3] The prognosis for hemolytic anemias varies on the cause of the illness as well as how early it is diagnosed and appropriately managed. Some Specific Complications 15% to 44% of paroxysmal nocturnal hemoglobinuria patients will have at least one thromboembolic event and it is a common cause of death. Thalassemia and sickle cell disease both can create a hypercoagulable state.[1] In patients with autoimmune hemolytic anemia, 11 to 20% of patients are reported to have thrombotic events.[4] Chronic hemolysis can produce excess free hemoglobin and iron can lead to iron and hemosiderin deposition in the kidneys that may impair kidney function.[1] Some people with hereditary spherocytosis are not diagnosed until adulthood when they begin to present with recurrent cholelithiasis.[1] Conclusions Hemolysis and hemolytic anemia have numerous etiologies. This includes infections, autoimmune diseases, hereditary diseases, medications, toxins, some envenomations, some cancers and mechanical destruction. The key to making the correct diagnosis is a complete patient and family history. Physical exam may be helpful in delineating cause in some cases. There are a number of laboratory tests that may be helpful but a blood smear may be particularly useful. Treatment will depend on the etiology and in most cases hematology consultation will be helpful or required. References [1] Baldwin C, Pandey J, Olarewaju O. Hemolytic Anemia. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558904/ [2] Ludlow JT, Wilkerson RG, Nappe TM. Methemoglobinemia. [Updated 2022 Aug 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK537317/ [3] Phillips J, Henderson AC. Hemolytic Anemia: Evaluation and Differential Diagnosis. Am Fam Physician. 2018;98(6):354-361. Retrieved from: https://www.aafp.org/pubs/afp/issues/2018/0915/p354.html [4] Autoimmune Hemolytic Anemias. N Engl J Med 385:1407-1419. October 7, 2021. Retrieved from: https://www.nejm.org/doi/10.1056/NEJMra2033982?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed [5] Sarkar RS, Philip J, Mallhi RS, Jain N. Drug-induced immune hemolytic anemia (Direct Antiglobulin Test positive). Med J Armed Forces India. 2013;69(2):190-192. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862930/ [6] Khalid F, Mahendraker N, Tonismae T. HELLP Syndrome. [Updated 2022 Jun 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK560615/ [7] Stanley M, Killeen RB, Michalski JM. Thrombotic Thrombocytopenic Purpura. [Updated 2022 Nov 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK430721/ [8] Chang JC. Disseminated intravascular coagulation: is it fact or fancy?. Blood Coagul Fibrinolysis. 2018;29(3):330-337. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/29621007/ [9] Thomas, M.R., Robinson, S. and Scully, M.A. (2016), How we manage thrombotic microangiopathies in pregnancy. Br J Haematol, 173: 821-830. Retrieved from: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14045 [6] Zayd L. Al-Nouri, Jessica A. Reese, Deirdra R. Terrell, Sara K. Vesely, James N. George; Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood 2015; 125 (4): 616–618. https://ashpublications.org/blood/article/125/4/616/33855/Drug-induced-thrombotic-microangiopathy-a [11] Herman TF, Javaid MU. Heinz Body. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK551622/ [12] Blood smear with typical schistocytes in TTP marked in blue. Central Hematology Laboratory Hemostasis Research Laboratory Bern University Hospital & University of Bern. March 5, 2013. Retrieved from: https://commons.wikimedia.org/wiki/File:Blood_smear_with_typical_schistocytes_in_TTP_marked_in_blue_1.tif [13] By Guy Waterval - Own work, Apache License 2.0, https://commons.wikimedia.org/w/index.php?curid=53224950 https://www.apache.org/licenses/LICENSE-2.0 initially published 5/28/2023