Lengthy Lives

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  • Helping Your Children Live to 100: A Guide for Parents

    As parents, we all want our children to live long, healthy lives. While there’s no guarantee of reaching centenarian status, there are many evidence-based interventions we can implement to give our kids the best shot at longevity. This guide explores key areas where parents can make a difference, from nutrition and lifestyle choices to disease prevention and safety.

    Nutrition: Building Blocks for a Long Life

    Whole Foods vs. Processed Foods

    A diet rich in whole, unprocessed foods forms the foundation of longevity nutrition. Research has shown that ultra-processed foods are associated with numerous health risks:

    • A systematic review found that higher consumption of ultra-processed foods was linked to increased risks of overweight, obesity, abdominal obesity, all-cause mortality, metabolic syndrome, depression, and various cancers[1].
    • Ultra-processed food intake was associated with a 62% increased risk of all-cause mortality in a study of nearly 20,000 Spanish university graduates[1].
    • A meta-analysis found that higher ultra-processed food intake was associated with increased risk of type 2 diabetes[1].

    To promote longevity, encourage your children to eat:

    1. Fruits and vegetables: Aim for 5 servings daily, focusing on a variety of colors.
    2. Whole grains: Choose brown rice, whole wheat bread, and oats over refined grains.
    3. Lean proteins: Include fish, poultry, legumes, and nuts.
    4. Healthy fats: Incorporate sources of unsaturated fats like avocados, olive oil, and fatty fish.

    Foods to Limit or Avoid

    Equally important is minimizing foods that can negatively impact health:

    1. Processed meats: Hot dogs, deli meats, and sausages are high in sodium and preservatives.
    2. Sugary drinks: Sodas, fruit juices, and sports drinks provide empty calories.
    3. Artificial sweeteners: These can potentially lead to metabolic issues.
    4. Fried foods: High in unhealthy fats, they increase heart disease risk.
    5. High-sugar cereals: Opt for low-sugar, whole-grain alternatives.

    The Dangers of Artificial Sweeteners and Fructose

    While artificial sweeteners may seem like a healthy alternative to sugar, research suggests otherwise:

    • A systematic review found that artificial sweetener consumption was associated with increased risk of type 2 diabetes, cardiovascular disease, and metabolic syndrome[2].
    • Frequent consumption of artificial sweeteners may lead to metabolic derangements and, paradoxically, weight gain[2].

    Fructose, especially in the form of high-fructose corn syrup, has been linked to various health issues:

    • Excessive fructose intake is associated with increased risk of obesity, diabetes, and non-alcoholic fatty liver disease[3].

    Preserved Foods and Cancer Risk

    Studies, particularly from Asia, have shown associations between preserved foods and cancer risk:

    • A meta-analysis found a 52% higher risk of gastric cancer associated with intake of pickled vegetables/foods, with stronger associations in Korea and China[4].
    • Consumption of cured meat was significantly associated with increased breast cancer risk in Hong Kong Chinese women[4].

    Physical Activity: Moving Towards Longevity

    Regular physical activity is crucial for long-term health. The Centers for Disease Control and Prevention (CDC) provides clear guidelines:

    • Children and adolescents ages 6 through 17 years should do 60 minutes or more of moderate-to-vigorous physical activity daily[5].

    This should include:

    • Aerobic activity: Most of the 60 minutes
    • Muscle-strengthening: At least 3 days per week
    • Bone-strengthening: At least 3 days per week

    Encouraging active play, participation in sports, and limiting screen time can help children meet these goals.

    Discouraging Illicit Drug Use and Risky Behaviors

    Tobacco and Alcohol Prevention

    Tobacco use remains a significant health threat to young people. In 2023, 10.0% of middle and high school students reported current use of any tobacco product[6]. To help prevent tobacco use:

    1. Start conversations early: Begin discussing the dangers of tobacco use when children are 5-7 years old.
    2. Be a role model: If you smoke, quit. Children of non-smoking parents are less likely to start smoking.
    3. Establish clear rules: Set firm expectations about not using tobacco and enforce consequences.
    4. Educate about industry tactics: Teach children to recognize and resist tobacco marketing strategies.

    Alcohol remains the most commonly used substance among adolescents. In 2023, about 19.9% of youth ages 14 to 15 reported having at least one drink in their lifetime[6]. To discourage underage drinking:

    1. Communicate openly: Discuss the risks of alcohol use and your expectations regularly.
    2. Set a good example: Model responsible alcohol use or abstinence.
    3. Monitor activities: Know where your children are and who they’re with, especially during teen years.
    4. Strengthen family bonds: Regular family activities and open communication can reduce the likelihood of substance use.

    Preventing Opioid Misuse

    The opioid epidemic has had devastating effects on communities across the United States. To help prevent opioid misuse among youth:

    1. Educate about risks: Discuss the dangers of prescription opioid misuse and illicit opioid use.
    2. Secure medications: Keep prescription medications, especially opioids, locked away and dispose of unused medications properly.
    3. Promote alternative pain management: Encourage non-opioid pain management strategies when appropriate.
    4. Support mental health: Address underlying mental health issues that may contribute to substance use.

    Disease Prevention

    Cancer Prevention

    While not all childhood cancers are preventable, certain strategies can reduce future risk:

    1. Sun protection: Use sunscreen, protective clothing, and limit sun exposure.
    2. Healthy diet: Emphasize fruits, vegetables, and whole grains.
    3. Physical activity: Maintain a healthy weight through regular exercise.
    4. Vaccinations: Ensure children receive HPV and Hepatitis B vaccines.
    5. Avoid tobacco exposure: Don’t smoke and avoid secondhand smoke.

    Vitamin D and Cancer Risk

    Vitamin D has been the subject of numerous studies regarding its potential role in cancer prevention:

    • A large clinical trial (VITAL) found that vitamin D supplementation reduced the incidence of advanced (metastatic or fatal) cancer, with the strongest risk reduction seen in individuals with normal weight[7].
    • Higher circulating levels of vitamin D (25-hydroxyvitamin D) have been associated with reduced risk of colorectal and bladder cancers[7].

    The current evidence suggests that maintaining adequate vitamin D levels may be beneficial for cancer prevention, but more research is needed to establish definitive recommendations. The National Academy of Sciences recommends daily vitamin D intakes of 600 IU for most age groups[7].

    Heart Disease Prevention

    Heart health in adulthood starts in childhood:

    1. Encourage a heart-healthy diet low in saturated fats and high in fruits, vegetables, and whole grains.
    2. Promote regular physical activity.
    3. Maintain a healthy weight.
    4. Monitor blood pressure and cholesterol if there’s a family history of heart disease.

    Safety and Accident Prevention

    Accidents are a leading cause of childhood mortality. Key safety measures include:

    1. Use appropriate car seats and teach road safety.
    2. Childproof your home to prevent falls, poisonings, and choking hazards.
    3. Teach water safety and ensure proper supervision around water.
    4. Store medications and household chemicals safely out of reach.
    5. Ensure proper helmet use for biking and other wheeled activities.

    Conclusion

    Helping our children live long, healthy lives involves a multifaceted approach encompassing nutrition, physical activity, disease prevention, safety, and overall lifestyle choices. By implementing these evidence-based strategies early in life, we can set our children on a path towards optimal health and longevity.

    Remember, it’s never too early to start these healthy habits, but it’s also never too late. Small, consistent changes can make a big difference over time. As parents, we have the power to shape our children’s health trajectories. Let’s use that power wisely to give them the best possible start in life.

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  • Lipid-Lowering Therapies Beyond Statins: A Comprehensive Review for Physicians

    As cardiovascular disease remains a leading cause of morbidity and mortality worldwide, optimizing lipid management is crucial for reducing atherosclerotic cardiovascular disease (ASCVD) risk. While statins are the cornerstone of lipid-lowering therapy, many patients require additional interventions to achieve target lipid levels or may not tolerate statins. This review examines the evidence for non-statin lipid-lowering therapies, including pharmacological agents, nutraceuticals, and dietary interventions.

    Importance of MACE Data

    When evaluating lipid-lowering therapies, it’s critical to focus on major adverse cardiovascular events (MACE) data rather than solely on lipid level changes. MACE typically includes a composite of cardiovascular death, non-fatal myocardial infarction (“heart attack”) and non-fatal stroke. Some studies also include hospitalization for unstable angina or coronary revascularization[13] (procedure to open clogged vessels). MACE endpoints provide a more clinically relevant measure of a therapy’s impact on patient outcomes compared to surrogate markers like LDL-C levels alone.

    Pharmacological Agents

    Ezetimibe

    Mechanism: Ezetimibe inhibits intestinal cholesterol absorption by targeting the Niemann-Pick C1-Like 1 (NPC1L1) protein[5].

    Efficacy: Ezetimibe typically reduces LDL-C by 15-20% when used as monotherapy (used alonea) and provides an additional 23-24% reduction when added to statin therapy[5][23].

    Outcomes: The IMPROVE-IT trial demonstrated that adding ezetimibe to simvastatin in patients with recent acute coronary syndrome (emergency when blood flow to heart is reduced) reduced LDL-C by 24% and lowered the risk of cardiovascular events by 6.4% over 7 years[28].

    Pleiotropic effects (not the primary effect or intention of drug) : Some studies suggest ezetimibe may have anti-inflammatory properties and improve endothelial function, though these effects are less well-established than for statins[42].

    Bempedoic Acid

    Mechanism: Bempedoic acid inhibits ATP citrate lyase (ACL), reducing cholesterol synthesis upstream of HMG-CoA reductase[21].

    Efficacy: In statin-intolerant patients, bempedoic acid reduces LDL-C by 21% compared to placebo[21].

    Outcomes: The CLEAR Outcomes trial showed a 13% relative reduction in MACE with bempedoic acid in statin-intolerant patients[21].

    Pleiotropic effects: Bempedoic acid may have anti-inflammatory properties, as evidenced by reductions in high-sensitivity C-reactive protein (hsCRP)[21].

    Colesevelam

    Mechanism: Colesevelam is a bile acid sequestrant that binds bile acids in the intestine, leading to increased bile acid excretion and upregulation of LDL receptors[27].

    Efficacy: Colesevelam reduces LDL-C by 15-18% as monotherapy and provides an additional 8-16% reduction when added to statin therapy[27].

    Outcomes: While colesevelam improves lipid profiles, large-scale cardiovascular outcome trials are lacking[27].

    Pleiotropic effects: Colesevelam has been shown to improve glycemic control in patients with type 2 diabetes, reducing HbA1c by 0.5-0.8%[22][41].

    PCSK9 Inhibitors

    Mechanism: PCSK9 inhibitors are monoclonal antibodies that prevent PCSK9-mediated degradation of LDL receptors, increasing LDL-C clearance from the bloodstream[40].

    Efficacy: PCSK9 inhibitors can reduce LDL-C by 50-60% when added to statin therapy[40].

    Outcomes: The FOURIER and ODYSSEY OUTCOMES trials demonstrated significant reductions in MACE with evolocumab and alirocumab, respectively, when added to statin therapy in high-risk patients[40].

    Pleiotropic effects: PCSK9 inhibitors may have anti-inflammatory effects and improve endothelial function, though more research is needed to confirm these potential benefits[40].

    Nutraceuticals and Supplements

    Red Yeast Rice

    Mechanism: Red yeast rice contains monacolin K, which is structurally identical to lovastatin and inhibits HMG-CoA reductase[19][24].

    Efficacy: Red yeast rice can reduce LDL-C by 15-25% depending on the monacolin K content[19][24].

    Outcomes: A meta-analysis of red yeast rice trials showed a 34% reduction in MACE and a 40% reduction in composite cardiac events[24].

    Safety concerns: The FDA does not regulate red yeast rice products, leading to variability in monacolin K content and potential contamination with citrinin, a nephrotoxic mycotoxin[19].

    Plant Sterols and Stanols

    Mechanism: Plant sterols and stanols compete with cholesterol for intestinal absorption, reducing cholesterol uptake[6].

    Efficacy: Consuming 2 grams of plant sterols or stanols daily can lower LDL-C by 5-15%[6][47].

    Outcomes: While plant sterols and stanols improve lipid profiles, large-scale cardiovascular outcome trials are lacking[6].

    Soluble Fiber

    Mechanism: Soluble fiber binds bile acids in the intestine, leading to increased bile acid excretion and upregulation of LDL receptors[47].

    Efficacy: Consuming 5-10 grams of soluble fiber daily can reduce LDL-C by 5-10%[47][49].

    Outcomes: While soluble fiber improves lipid profiles, its direct impact on MACE has not been established in large-scale trials[49].

    Omega-3 Fatty Acids

    Mechanism: Omega-3 fatty acids reduce hepatic triglyceride synthesis and increase fatty acid oxidation[53].

    Efficacy: High-dose omega-3 fatty acids (4 grams daily) can reduce triglycerides by 30-50%[53].

    Outcomes: The REDUCE-IT trial demonstrated a 25% relative risk reduction in MACE with 4 grams of icosapent ethyl (a highly purified EPA) in high-risk patients with elevated triglycerides[53].

    Other Supplements

    Several other supplements have shown potential lipid-lowering effects, though evidence for cardiovascular benefit is limited:

    • Berberine: May reduce LDL-C by 20-30%[10]
    • Garlic extract: May modestly reduce total cholesterol and LDL-C[10]
    • Green tea extract: May have modest LDL-C lowering effects[10]
    • Niacin: Can increase HDL-C and lower triglycerides, but has not shown cardiovascular benefit in recent trials[53]

    Dietary Interventions

    Mediterranean Diet

    The Mediterranean diet, characterized by high consumption of olive oil, fruits, vegetables, whole grains, and moderate consumption of fish and poultry, has been associated with improved cardiovascular outcomes[47][56].

    Efficacy: While the direct impact on lipid levels varies, adherence to a Mediterranean diet has been associated with a 30% reduction in MACE in high-risk individuals[47].

    Plant-Based Diets

    Vegetarian and vegan diets have been shown to improve lipid profiles and may reduce cardiovascular risk[52].

    Efficacy: A meta-analysis of randomized controlled trials found that vegetarian and vegan diets reduced total cholesterol by 7%, LDL-C by 10%, and apolipoprotein B by 14% compared to omnivorous diets[52].

    Portfolio Diet

    The Portfolio Diet combines several cholesterol-lowering foods, including plant sterols, soy protein, viscous fibers, and nuts[49].

    Efficacy: The Portfolio Diet has been shown to reduce LDL-C by 20-30%, comparable to the effect of a low-dose statin[49].

    Other Dietary Strategies

    • Replacing saturated fats with unsaturated fats can reduce LDL-C by 9-16%[47][49]
    • Increasing intake of fruits and vegetables may modestly improve lipid profiles[47]
    • Consuming 1.5-2 ounces of tree nuts daily can reduce LDL-C by 3-5%[49]

    Conclusion

    While statins remain the cornerstone of lipid-lowering therapy, a wide array of non-statin interventions can effectively improve lipid profiles and reduce cardiovascular risk. When selecting therapies, physicians should consider the strength of evidence for MACE reduction, individual patient characteristics, and potential pleiotropic effects. Combining pharmacological agents with evidence-based dietary interventions and nutraceuticals may provide additive benefits in managing dyslipidemia and reducing ASCVD risk.

    As our understanding of lipid metabolism and cardiovascular disease continues to evolve, ongoing research into novel therapies and combinations will further refine our approach to lipid management. Physicians should stay informed about emerging evidence and guidelines to provide optimal care for patients at risk for ASCVD.

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    [43] Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar https://www.jacc.org/doi/abs/10.1016/j.jacc.2020.11.056
    [44] Are We Using Ezetimibe As Much As We Should? – Sage Journals https://journals.sagepub.com/doi/10.1177/11772719241257410
    [45] [PDF] Dietary intervention to lower serum cholesterol – RACGP https://www.racgp.org.au/getattachment/f8f6c03d-08b4-49b1-abb4-35039b0f4928/Lower-serum-cholesterol.aspx
    [46] How to Lower Cholesterol with Diet – MedlinePlus https://medlineplus.gov/howtolowercholesterolwithdiet.html
    [47] Does the Mediterranean Diet Have Any Effect on Lipid Profile … https://pmc.ncbi.nlm.nih.gov/articles/PMC10222807/
    [48] Vegetarian and vegan diets may lower cholesterol levels https://www.health.harvard.edu/heart-health/vegetarian-and-vegan-diets-may-lower-cholesterol-levels
    [49] Diet and Exercise in the Management of Hyperlipidemia – AAFP https://www.aafp.org/pubs/afp/issues/2010/0501/p1097.html
    [50] Cholesterol – healthy eating tips – Better Health Channel https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/cholesterol-healthy-eating-tips
    [51] LDL cholesterol: Mediterranean diet may not affect levels https://www.medicalnewstoday.com/articles/does-a-mediterranean-diet-really-help-lower-bad-cholesterol
    [52] Vegetarian or vegan diets and blood lipids: a meta-analysis of … https://pubmed.ncbi.nlm.nih.gov/37226630/
    [53] Alternative Treatments for High Cholesterol – WebMD https://www.webmd.com/cholesterol-management/high-cholesterol-alternative-therapies
    [54] Association between Dietary Intake and Lipid-Lowering Therapy https://pmc.ncbi.nlm.nih.gov/articles/PMC6724025/
    [55] Prevention and Treatment of High Cholesterol (Hyperlipidemia) https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia
    [56] Mediterranean diet: MedlinePlus Medical Encyclopedia https://medlineplus.gov/ency/patientinstructions/000110.htm
    [57] The Role of Specific Components of a Plant-Based Diet in … https://pmc.ncbi.nlm.nih.gov/articles/PMC7551487/
    [58] 6 common “heart-health” supplements ineffective at lowering … https://newsroom.heart.org/news/6-common-heart-health-supplements-ineffective-at-lowering-cholesterol-compared-to-statins
    [59] Nutrition interventions for adults with dyslipidemia – PubMed https://pubmed.ncbi.nlm.nih.gov/37271600/
    [60] Effectiveness of altering serum cholesterol levels without drugs – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC1312230/
    [61] The Impact of the Mediterranean Diet and Lifestyle Intervention on … https://www.mdpi.com/1422-0067/25/2/1338
    [62] Portfolio Diet: Lower Your Cholesterol One Bite at a Time with Plant … https://www.orlandohealth.com/content-hub/portfolio-diet-lower-your-cholesterol-one-bite-at-a-time-with-plant-based-eating
    [63] 8 Natural Cholesterol Reducers – Healthline https://www.healthline.com/health/high-cholesterol/natural-cholesterol-reducers
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    [65] Mediterranean diet for heart health – Mayo Clinic https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801
    [66] Top 10 Plant-Based Foods to Lower Cholesterol https://www.purelyplanted.com/post/top-10-plant-based-foods-to-lower-cholesterol
    [67] Best supplements for lowering cholesterol – MedicalNewsToday https://www.medicalnewstoday.com/articles/cholesterol-lowering-supplements
    [68] Cooking to Lower Cholesterol | American Heart Association https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cooking-to-lower-cholesterol
    [69] Can the Mediterranean Diet Lower Your Cholesterol? https://www.verywellhealth.com/mediterranean-diet-to-reduce-cholesterol-697647
    [70] Plant-Based Diets and Your Cholesterol – WebMD https://www.webmd.com/cholesterol-management/features/plant-based-diets-and-cholesterol
    [71] Mediterranean Meal Plan to Lower Cholesterol – EatingWell https://www.eatingwell.com/article/7740264/mediterranean-meal-plan-to-lower-cholesterol/
    [72] Lower cholesterol with a plant-based diet, study says – CNN https://edition.cnn.com/2023/05/24/health/vegetarian-vegan-diet-reduce-cholesterol-wellness/index.html
    [73] Lipid Management in Peripheral Artery Disease: A Focus on Recent … https://www.acc.org/Latest-in-Cardiology/Articles/2024/08/19/10/45/Lipid-Management-in-Peripheral-Artery-Disease
    [74] Association of Major Adverse Cardiac Events up to 5 Years in … https://www.ahajournals.org/doi/10.1161/JAHA.118.010541
    [75] More- Versus Less-Intensive Lipid-Lowering Therapy – AHA Journals https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.118.005460
    [76] Association of Treatment Intensity and Adherence to Lipid-Lowering … https://pmc.ncbi.nlm.nih.gov/articles/PMC8107155/
    [77] Lipid-lowering therapies for cardiovascular disease prevention and … https://pmc.ncbi.nlm.nih.gov/articles/PMC10575662/
    [78] Defining the need for cardiovascular event definitions https://academic.oup.com/ehjqcco/article/10/2/105/7596555
    [79] Risk of major adverse cardiovascular events associated … – BMJ Open https://bmjopen.bmj.com/content/13/11/e064541
    [80] Heart Failure and Major Adverse Cardiovascular Events in Atrial … https://www.mdpi.com/2227-9059/11/7/1825
    [81] Occurence of First and Recurrent Major Adverse Cardiovascular … https://jamanetwork.com/journals/jamacardiology/fullarticle/2754760
    [82] Comparison of Major Adverse Cardiac Events Between … https://jamanetwork.com/journals/jamacardiology/fullarticle/2738103
    [83] Effectiveness of lipid-lowering therapy on mortality and major … https://pmc.ncbi.nlm.nih.gov/articles/PMC10660972/
    [84] Navigating the “MACE” in Cardiovascular Outcomes Trials and … https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.13740
    [85] Reductions in Atherogenic Lipids and Major Cardiovascular Events https://www.ahajournals.org/doi/10.1161/circulationaha.116.024604
    [86] Prediction of Major Adverse Cardiovascular Events in Patients With … https://www.ahajournals.org/doi/10.1161/CIRCGEN.121.003546

  • Statins: A Look at Outcomes, Efficacy, and Beyond

    Everyday (including today) I must build a case for the timely use of a statin agent, overcoming the vilification these medicines face in popular culture. In reality, compelling evidence, based on well conducted studies, have shown the profound beneficial effects of these medications. Indeed, statins have revolutionized cardiovascular disease prevention and treatment since their introduction. This post will delve into the wealth of data from statin trials, exploring their efficacy, pleiotropic effects, and key concepts like number needed to treat (NNT). We’ll also examine specific trials and rank statins by their power in reducing cardiovascular events.

    Statin Efficacy: The Big Picture

    Numerous large-scale trials have consistently demonstrated the efficacy of statins in reducing cardiovascular events. The evidence is particularly strong for secondary prevention (in patients with established cardiovascular disease) but is also significant for primary prevention in high-risk individuals[1][2].

    Key findings from major statin trials include:

    1. Reduction in major adverse cardiovascular events (MACE)
    2. Decrease in all-cause mortality (in some trials)
    3. Lowering of LDL cholesterol levels
    4. Potential pleiotropic effects beyond lipid-lowering

    The ASCOT-LLA Trial: A Closer Look

    The Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) was a landmark study that demonstrated the benefits of statins in primary prevention[8][9]. This trial randomized hypertensive patients with relatively low cholesterol levels to atorvastatin 10 mg or placebo.

    Key ASCOT-LLA findings:

    • 36% reduction in the primary endpoint (non-fatal myocardial infarction and fatal coronary heart disease)
    • Early separation of event curves, suggesting rapid onset of benefit (in as few as 2 months)
    • Persistent benefit even after trial termination, indicating a potential “legacy effect”

    The rapid separation of event curves in ASCOT-LLA is particularly intriguing. It suggests that statins may provide cardiovascular protection even before their full lipid-lowering effects are realized, supporting the concept of pleiotropic effects[8].

    Pleiotropic Effects: Beyond Lipid-Lowering

    Statins may exert cardiovascular protective effects independent of LDL-C lowering, known as “pleiotropic” effects[7]. These include:

    1. Improved endothelial function (cells that line the arteries)
    2. Antioxidant properties
    3. Anti-inflammatory effects
    4. Plaque stabilization

    While some studies support these pleiotropic effects, the clinical relevance remains debated. Some trials have shown greater benefits with high-dose statins compared to lower doses plus ezetimibe, despite similar LDL-C lowering[7]. However, other studies have not found such differences, leaving the question of pleiotropy open to further research.

    Number Needed to Treat (NNT)

    The NNT is a valuable concept in understanding the real-world impact of statin therapy. It represents the number of patients who need to be treated to prevent one adverse event.

    In the UK arm of ASCOT-LLA, the NNT to prevent one death from atorvastatin treatment for 3.3 years was 286[1]. This number improved over time, highlighting the cumulative benefit of statin therapy.

    A meta-analysis of primary prevention trials found that treating 100 adults (aged 50-75 years) with a statin for 2.5 years prevented 1 MACE in 1 adult[2]. This translates to an NNT of 100 over 2.5 years for primary prevention.

    Major Statin Trials: A Summary

    1. 4S (Scandinavian Simvastatin Survival Study): Demonstrated mortality (reducing death) benefit in secondary prevention with simvastatin[8].
    2. WOSCOPS (West of Scotland Coronary Prevention Study): Showed pravastatin’s efficacy in primary prevention[2].
    3. CARE (Cholesterol and Recurrent Events): Established pravastatin’s benefit in patients with average cholesterol levels post-MI[8].
    4. LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease): Confirmed pravastatin’s long-term benefits in a broad range of patients[8].
    5. JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin): Demonstrated rosuvastatin’s efficacy in primary prevention for patients with elevated C-reactive protein[2].
    6. PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy): Compared aggressive (atorvastatin 80 mg) vs. moderate (pravastatin 40 mg) statin therapy[5].
    7. ASCOT-LLA: Showed atorvastatin’s benefit in primary prevention for hypertensive patients[8][9].

    Ranking Statins by Event Reduction

    While all statins have shown efficacy, some appear more potent in reducing cardiovascular events:

    1. Atorvastatin (high-intensity)
    2. Rosuvastatin (high-intensity)
    3. Simvastatin (moderate to high-intensity)
    4. Pravastatin (low to moderate-intensity)
    5. Fluvastatin (low-intensity)

    This ranking is based on their lipid-lowering potency and evidence from comparative trials[3][5]. However, it’s important to note that individual patient factors should guide statin selection. Our preference is for rosuvastatin, due to less musculoskeletal effects and profound reduction of LDL, even at lower doses.

    CVA vs. MACE Data

    While statins consistently reduce MACE, or major adverse cardiac events, (which typically includes cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), their effect on cerebrovascular accidents (CVA) alone is less pronounced.

    Most trials show a significant reduction in overall MACE, but the effect on stroke (CVA) is often smaller or non-significant when analyzed separately. For instance, in ASCOT-LLA, while there was a significant reduction in MACE, the reduction in fatal and non-fatal stroke was not statistically significant[8][9].

    In conclusion, the wealth of data from statin trials provides strong evidence for their efficacy in reducing cardiovascular events, particularly in high-risk individuals and for secondary prevention. While questions remain about the extent of their pleiotropic effects and the optimal approach to primary prevention, statins remain a cornerstone of cardiovascular risk reduction. As with all medical interventions, the decision to initiate statin therapy should be based on individual patient factors and shared decision-making.

    Sources
    [1] 11-year mortality follow-up of the lipid-lowering arm in the UK … https://academic.oup.com/eurheartj/article/32/20/2525/487760?login=false
    [2] Evaluation of Time to Benefit of Statins for the Primary Prevention of … https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2773065
    [3] Comparative Effectiveness of Statin Therapy in Reducing … https://www.heraldopenaccess.us/openaccess/comparative-effectiveness-of-statin-therapy-in-reducing-cardiovascular-events
    [4] Ongoing Clinical Trials of the Pleiotropic Effects of Statins – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC1993933/
    [5] Improving outcomes through statin therapy – a review of ongoing trials https://academic.oup.com/eurheartjsupp/article/6/suppl_A/A28/386696
    [6] Time to Benefit of Statins for Primary Prevention of Cardiovascular … https://www.acc.org/latest-in-cardiology/journal-scans/2020/11/24/18/25/evaluation-of-time-to-benefit-of-statins
    [7] Pleiotropic Effects of Statins on the Cardiovascular System – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC5467317/
    [8] Long-term results from statin trials: answers but more unresolved … https://academic.oup.com/eurheartj/article/32/20/2479/487295
    [9] Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2010/02/22/19/05/ASCOT–Lipid-Arm

  • Understanding and Managing Chronic Kidney Disease

    A common conversation I have with my patients involves the implications of the eGFR, or estimated glomerular filtration rate. This value is on every chemistry panel we order and is often found to be diminished, frequently unexpectedly, on blood work. This can be anxiety provoking, and is certainly confusing, inasmuch as this dysfunction is usually asymptomatic and has significant health implications.

    Chronic Kidney Disease (CKD) is a progressive condition affecting millions worldwide. This guide aims to demystify CKD, its stages, and evidence-based strategies for management.

    The Stages of CKD and the Importance of eGFR

    Chronic Kidney Disease is classified into five stages based on the estimated Glomerular Filtration Rate (eGFR), a measure of how well the kidneys filter waste from the blood. The eGFR is calculated using serum creatinine levels, age, sex, and race.

    CKD stages:

    1. Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m²)
    2. Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m²)
    3. Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73 m²)
    4. Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73 m²)
    5. Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m²)
    6. Stage 5: Kidney failure (GFR <15 mL/min/1.73 m² or dialysis)

    Understanding these stages is crucial for diagnosis and treatment planning. As the disease progresses, the risk of complications increases, making early detection and intervention vital.

    Preserving Kidney Function: Evidence-Based Strategies

    Lifestyle Modifications

    1. Blood Pressure Control: Maintaining optimal blood pressure is crucial in slowing CKD progression.
    2. Glycemic Control: For diabetic patients, tight glycemic (blood sugar) control can significantly reduce the risk of kidney damage.
    3. Dietary Changes: A low-sodium, low-protein diet can help reduce the workload on the kidneys.
    4. Exercise: Regular physical activity can improve overall health and help manage comorbidities like hypertension and diabetes.

    Pharmacological Interventions: medicines to treat CKD

    Several medications have shown promise in preserving kidney function:

    1. ACE Inhibitors and ARBs: These medications help control blood pressure and reduce proteinuria, slowing CKD progression.
    2. SGLT2 Inhibitors: Originally developed for diabetes, these drugs have shown remarkable renoprotective effects in both diabetic and non-diabetic CKD patients.
    3. Mineralocorticoid Receptor Antagonists (MRAs): Drugs like spironolactone and eplerenone can help manage resistant hypertension and reduce proteinuria.
    4. Finerenone: A non-steroidal MRA that has shown promising results in reducing both renal and cardiovascular outcomes in patients with diabetic kidney disease.

    Dietary Considerations for Advanced CKD

    As kidney function declines, dietary restrictions become more crucial:

    1. Protein Intake: Moderate protein consumption is recommended. Too much protein can overwork the kidneys, while too little may lead to malnutrition.
    2. Sodium Restriction: Limiting sodium (salt) helps control blood pressure and reduces fluid buildup.
    3. Potassium Management: Foods high in potassium (e.g., oranges, potatoes, tomatoes) should be limited as excess potassium can cause heart problems.
    4. Phosphorus Control: Reduce intake of foods high in phosphorus (meat, dairy, beans, nuts, whole-grain bread) to prevent bone weakening and blood vessel damage.
    5. Fluid Restriction: In advanced stages, limiting fluid intake becomes necessary to prevent fluid buildup.

    Foods to Focus On:

    • Fruits: berries, grapes, apples, plums
    • Vegetables: cauliflower, onions, eggplant, turnips
    • Proteins: lean meats (poultry, fish), eggs, unsalted seafood
    • Carbohydrates: white bread, unsalted crackers, pasta

    Things to Avoid

    1. Artificial Sweeteners: While the relationship between artificial sweeteners and CKD risk is not definitively established, some studies suggest a potential link. Caution is advised.
    2. Proton Pump Inhibitors (PPIs): Long-term use of PPIs has been associated with an increased risk of CKD. If prescribed, discuss the risks and benefits with your healthcare provider.
    3. Herbal Supplements: Many herbal supplements can be harmful to kidney function. Avoid supplements like astragalus, horsetail, licorice root, and others without consulting a healthcare professional.
    4. High-Potassium Foods: In advanced stages, limit intake of high-potassium foods like bananas, oranges, and potatoes.
    5. Phosphate-Rich Foods: Reduce consumption of dairy products, nuts, and cola drinks.
    6. Excessive Protein: Especially from red meat sources.
    7. Alcohol: Limit or avoid alcohol consumption as it can interfere with kidney function and medications.
    8. Raw or Unpasteurized Foods: These may increase the risk of foodborne illnesses in immunocompromised individuals.
    9. Nephrotoxic Medications: NSAIDs, certain antibiotics, and contrast dyes should be used cautiously or avoided in CKD patients.
    10. Smoking: Tobacco use can accelerate kidney damage and should be discontinued.

    When to Consult a Nephrologist

    Referral to a nephrologist (kidney specialist) is typically recommended in the following situations:

    1. eGFR <30 mL/min/1.73 m² (Stage 4 or 5 CKD)
    2. Rapid decline in kidney function
    3. Persistent proteinuria (protein in urine)
    4. Difficult-to-control hypertension
    5. Recurrent or extensive nephrolithiasis (kidney stones)
    6. Hereditary kidney disease

    Early referral has been associated with better outcomes, including reduced mortality rates in the first 90 days of dialysis.

    Workup of Kidney Dysfunction

    A comprehensive evaluation of kidney function typically includes:

    Laboratory Tests:

      • Serum creatinine and eGFR calculation
      • Urine albumin-to-creatinine ratio (to measure protein loss in urine)
      • Complete blood count
      • Serum electrolytes
      • Lipid profile
      • Hemoglobin A1C (for diabetic patients)

      Imaging studies

      • Renal ultrasonography to evaluate kidney size and structure
      • CT or MRI scans in specific cases

      Additional Tests (as needed):

        • 24-hour urine collection for protein and creatinine clearance
        • Kidney biopsy in cases where the etiology is unclear

        Conclusion

        Chronic Kidney Disease is a complex condition that requires a multifaceted approach to management. By understanding the stages of CKD, the importance of eGFR, and implementing evidence-based strategies, we can significantly improve outcomes for our patients. Early detection, lifestyle modifications, appropriate medication use, and timely referral to nephrology can all contribute to preserving kidney function and enhancing quality of life for those living with CKD.

        Remember, each patient is unique, and treatment plans should be tailored to individual needs and circumstances. By staying informed about the latest advancements in CKD management, we can provide the best possible care for our patients.

        Sources

        1. National Kidney Foundation. (2023). Kidney Failure Risk Factor: Estimated Glomerular Filtration Rate (eGFR). Retrieved from https://www.kidney.org/kidney-failure-risk-factor-estimated-glomerular-filtration-rate-egfr
        2. Webster, A. C., Nagler, E. V., Morton, R. L., & Masson, P. (2017). Chronic Kidney Disease. The Lancet, 389(10075), 1238-1252.
        3. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. (2013). KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International Supplements, 3(1), 1-150.
        4. Brenner, B. M., Cooper, M. E., de Zeeuw, D., et al. (2001). Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. New England Journal of Medicine, 345(12), 861-869.
        5. Perkovic, V., Jardine, M. J., Neal, B., et al. (2019). Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine, 380(24), 2295-2306.
        6. Bakris, G. L., Agarwal, R., Anker, S. D., et al. (2020). Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. New England Journal of Medicine, 383(23), 2219-2229.
        7. National Institute of Diabetes and Digestive and Kidney Diseases. (2022). Eating Right for Chronic Kidney Disease. Retrieved from https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/eating-nutrition
        8. Xie, Y., Bowe, B., Li, T., Xian, H., Yan, Y., & Al-Aly, Z. (2016). Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD. Journal of the American Society of Nephrology, 27(10), 3153-3163.
        9. Kidney Research UK. (2023). Healthy eating for kidney patients. Retrieved from https://www.kidneyresearchuk.org/kidney-health-information/living-with-kidney-disease/how-can-i-help-myself/healthy-eating-for-kidney-patients/
        10. Smart, N. A., Dieberg, G., Ladhani, M., & Titus, T. (2014). Early referral to specialist nephrology services for preventing the progression to end-stage kidney disease. Cochrane Database of Systematic Reviews, (6).
        11. Levey, A. S., & Coresh, J. (2012). Chronic kidney disease. The Lancet, 379(9811), 165-180.
        12. Centers for Disease Control and Prevention. (2023). Diabetes and Kidney Disease: What to Eat. Retrieved from https://www.cdc.gov/diabetes/healthy-eating/diabetes-and-kidney-disease-food.html
        13. National Kidney Foundation. (2023). Herbal Supplements and Kidney Disease. Retrieved from https://www.kidney.org/kidney-topics/herbal-supplements-and-kidney-disease

      1. Palmitoylethanolamide (PEA): A Promising Approach to Neuropathic Pain Management

        Neuropathic pain remains one of the most challenging conditions for clinicians to treat effectively. Traditional medications often provide only symptomatic relief without addressing the underlying pathology. However, emerging research on palmitoylethanolamide (PEA) offers a promising new avenue for both symptom management and potential disease modification in neuropathic pain conditions.

        What is Palmitoylethanolamide?

        Palmitoylethanolamide is an endogenous fatty acid amide, meaning it’s a naturally occurring compound in the body. It belongs to the class of N-acylethanolamines, which are bioactive lipid mediators[3]. PEA is synthesized on demand within cell membranes and acts locally to maintain cellular homeostasis.

        Mechanism of Action

        PEA’s effects on neuropathic pain are multifaceted, involving several key mechanisms:

        1. PPAR-α Activation: PEA primarily acts by binding to and activating the peroxisome proliferator-activated receptor alpha (PPAR-α) in the cell nucleus. This nuclear receptor plays a crucial role in regulating inflammation and pain signaling[9].

        2. Mast Cell Stabilization: PEA inhibits the release of pro-inflammatory mediators from activated mast cells. This is particularly important in neuropathic pain, where mast cell infiltration and activation contribute to nerve sensitization[3].

        3. Microglial Modulation: In models of spinal cord injury and neuroinflammation, PEA treatment has been shown to inhibit microglial activation. Microglia are immune cells in the central nervous system that, when overactivated, can contribute to chronic pain states[9].

        4. Neuroprotection: PEA exhibits neuroprotective properties, preventing neurotoxicity and neurodegeneration. This is crucial for potentially halting or reversing the progression of neuropathic conditions[10].

        Clinical Applications

        PEA has demonstrated efficacy in a wide range of neuropathic pain conditions, including diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery syndrome, dental pains, neuropathic pain in stroke and multiple sclerosis, chronic pelvic pain, postherpetic neuralgia, and vaginal pains[3][4].

        Disease Modification Potential

        Unlike many conventional pain medications that simply mask symptoms, PEA shows promise in actually modifying the course of neuropathic pain conditions. In animal models of sciatic nerve injury, PEA treatment has been associated with improved myelin sheath thickness, increased axonal diameter, and a higher number of nerve fibers[10]. This suggests that PEA may support nerve regeneration and repair, potentially halting or reversing the progression of neuropathic conditions.

        Safety Profile

        One of the most remarkable aspects of PEA is its excellent safety profile. As an endogenous compound also found in foods like eggs and milk, PEA has shown no serious side effects in clinical trials. Furthermore, no significant drug-drug interactions have been reported, making it a potentially safe option for long-term use or as part of combination therapies[5].

        Clinical Evidence

        A meta-analysis of randomized controlled trials found that PEA was associated with significantly greater pain reduction compared to inactive control conditions (WMD = 2.03, 95% CI: 1.19 – 2.87, z = 4.75, P < 0.001)[5]. Another study on patients with diabetic or traumatic neuropathic pain showed significant improvements in pain scores and quality of life after 40 days of PEA treatment[4].

        Conclusion

        Palmitoylethanolamide represents a promising approach to neuropathic pain management that goes beyond symptom control. Its broad spectrum of activity, potential for disease modification, and excellent safety profile make it an attractive option for clinicians and patients alike. While more research is needed to fully elucidate its mechanisms and optimize treatment protocols, the current evidence suggests that PEA could be a valuable addition to the neuropathic pain treatment arsenal.

        Sources

        [1] Ultramicronized Palmitoylethanolamide in the Management … – MDPI https://www.mdpi.com/2077-0383/13/10/2787

        [2] Novel Approach to the Treatment of Neuropathic Pain Using a … https://www.mdpi.com/1422-0067/24/6/5503

        [3] Practical update on oral palmythopylethanolamide (PEAum) in the … https://www.mpainjournal.com/actualizacion-practica-sobre-la-palmitoiletanolamida-peaum-oral-en-el-manejo-del-dolor-cronico-revision-narrativa1163

        [4] Palmitoylethanolamide in the Treatment of Chronic Pain Caused by … https://academic.oup.com/painmedicine/article/13/9/1121/1864240?login=false

        [5] [PDF] Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis https://www.painphysicianjournal.com/current/pdf?article=NDUwMg%3D%3D&journal=106

        [6] [PDF] Effect of palmitoylethanolamide on inflammatory and neuropathic … https://ekja.org/upload/pdf/kjae-70-561.pdf

        [7] Palmitoylethanolamide in the Treatment of Chronic Pain https://pmc.ncbi.nlm.nih.gov/articles/PMC10053226/

        [8] Palmitoylethanolamide (PEA) in the treatment of neuropathic pain https://journals.sagepub.com/doi/full/10.1177/02601060211019669

        [9] Therapeutic utility of palmitoylethanolamide in the treatment of … https://pmc.ncbi.nlm.nih.gov/articles/PMC3500919/

        [10] [PDF] Palmitoylethanolamide, a Special Food for Medical Purposes, in the … https://www.painphysicianjournal.com/current/pdf?article=MjUxMw%3D%3D&journal=94

      2. NAD+: Can it help with the aging process?

        Nicotinamide adenine dinucleotide (NAD+) has received profound attention in the realm of longevity research and anti-aging supplements. This essential coenzyme plays a crucial role in cellular energy production and various biological processes. As we age, our NAD+ levels naturally decline, which has led researchers to investigate whether boosting NAD+ could be a key to healthier aging. Let’s dive into the science behind NAD+ and explore its potential benefits and risks.

        What is NAD+?

        NAD+ is a coenzyme found in all living cells. It’s involved in hundreds of metabolic processes, including:

        – Converting food into energy

        – Repairing DNA damage

        – Supporting cellular stress responses

        – Regulating circadian rhythms

        Think of NAD+ as a cellular multitool, essential for keeping our biological machinery running smoothly.

        NAD+ Decline

        As we age, our NAD+ levels naturally decrease. This decline has been associated with various age-related conditions and diseases[1]. Some factors that contribute to NAD+ depletion include:

        – Oxidative stress

        – DNA damage

        – Inflammation

        – Metabolic dysfunction

        Potential Benefits of NAD+ Supplementation

        Research suggests that boosting NAD+ levels might help counteract some aspects of aging and improve overall health. Here are some potential benefits:

        1. Improved Cardiovascular Health

        NAD+ plays a crucial role in maintaining heart health. Studies have shown that NAD+ supplementation may help reduce blood pressure and arterial stiffness, two important markers of cardiovascular health[2].

        2. Enhanced Cognitive Function

        NAD+ is essential for proper brain function. Some research suggests that increasing NAD+ levels might help protect against age-related cognitive decline and neurodegenerative diseases[3].

        3. Increased Energy and Metabolism

        As NAD+ is crucial for energy production in cells, boosting its levels may help improve overall energy levels and metabolism[4].

        4. Better Muscle Function

        NAD+ is important for maintaining muscle health and function. Some studies have shown that NAD+ supplementation may help improve muscle strength and endurance, particularly in older adults[5].

        5. Potential Longevity Effects

        While more research is needed, some animal studies have suggested that boosting NAD+ levels might extend lifespan and improve overall health in later years[6].

        The Science Behind NAD+ Supplementation

        NAD+ itself isn’t easily absorbed by the body when taken orally. Instead, researchers have focused on precursor molecules that the body can use to produce NAD+. The two most studied precursors are:

        1. Nicotinamide Riboside (NR)

        2. Nicotinamide Mononucleotide (NMN)

        These precursors have shown promise in increasing NAD+ levels in various tissues[7]. Here’s a simplified explanation of how they work:

        1. You take an NAD+ precursor supplement (NR or NMN).

        2. Your body absorbs the precursor and converts it into NAD+.

        3. Cells use the increased NAD+ to power various biological processes.

        Clinical Evidence

        Several clinical trials have investigated the effects of NAD+ precursor supplementation in humans. Here are some key findings:

        – A study on healthy middle-aged and older adults found that chronic supplementation with nicotinamide riboside (NR) was well-tolerated and effectively increased NAD+ metabolism[8].

        – Another trial showed that NMN supplementation increased blood NAD+ concentrations and improved physical performance in middle-aged adults.

        – Research has also suggested that NAD+ precursors might help improve insulin sensitivity and reduce the risk of metabolic disorders.

        Potential Risks and Side Effects

        While NAD+ precursor supplements are generally considered safe, it’s important to note potential risks and side effects:

        – Common side effects may include nausea, fatigue, headaches, and gastrointestinal discomfort.

        – High doses of nicotinamide (a form of vitamin B3 and NAD+ precursor) may inhibit sirtuins, proteins that play a role in longevity.

        – There’s a theoretical concern that boosting NAD+ levels might promote the growth of existing cancers, although this hasn’t been observed in human studies[1].

        Conclusion

        The research on NAD+ and its precursors is exciting and promising. While more studies are needed to fully understand the long-term effects and optimal dosing, the current evidence suggests that NAD+ supplementation could play a role in healthy aging and disease prevention.

        As with any supplement, it’s crucial to consult with a healthcare professional before starting NAD+ precursor supplementation, especially if you have existing health conditions or are taking medications.

        Remember, while supplements can be beneficial, they’re not a magic bullet. A healthy lifestyle, including a balanced diet, regular exercise, and good sleep habits, remains the foundation of healthy aging.

        Sources

        [1] Dietary Supplementation With NAD+-Boosting Compounds in Humans https://pubmed.ncbi.nlm.nih.gov/37068054/

        [2] Chronic nicotinamide riboside supplementation is well-tolerated and … https://www.nature.com/articles/s41467-018-03421-7

        [3] NAD+ in Aging: Molecular Mechanisms and Translational Implications https://pmc.ncbi.nlm.nih.gov/articles/PMC7494058/

        [4] Possible Adverse Effects of High-Dose Nicotinamide – PubMed Central https://pmc.ncbi.nlm.nih.gov/articles/PMC7277745/

        [5] Evaluation of safety and effectiveness of NAD in different clinical … https://pubmed.ncbi.nlm.nih.gov/37971292/

        [6] Potential Synergistic Supplementation of NAD+ Promoting … – PubMed https://pubmed.ncbi.nlm.nih.gov/36678315/

        [7] NAD+ Metabolism in Cardiac Health, Aging, and Disease | Circulation https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056589

        [8] The efficacy and safety of β-nicotinamide mononucleotide (NMN … https://pubmed.ncbi.nlm.nih.gov/36482258/

      3. The Hidden Dangers of Artificial Sweeteners

        The Hidden Dangers of Artificial Sweeteners

        In recent years, artificial sweeteners have gained popularity as a sugar substitute, marketed as a healthier alternative for weight management and diabetes control. However, mounting evidence suggests that these sweeteners may pose significant health risks, potentially contributing to the very conditions they were designed to prevent. This blog post delves into the dangers of artificial sweeteners, examining their effects on diabetes risk, kidney function, cardiovascular health, and obesity.

        Artificial Sweeteners and Diabetes Risk

        Contrary to their intended purpose of helping manage blood sugar levels, artificial sweeteners may actually increase the risk of developing type 2 diabetes (T2D). A large-scale prospective study conducted in France, involving 105,588 participants, found alarming associations between artificial sweetener consumption and T2D risk[5].

        The study revealed that individuals consuming higher amounts of artificial sweeteners (above 16.4 mg/day for men and 18.5 mg/day for women) had a 69% higher risk of developing T2D compared to non-consumers. This increased risk was observed for total artificial sweetener intake as well as for individual sweeteners:

        – Aspartame: 63% increased risk

        – Acesulfame-K: 70% increased risk

        – Sucralose: 34% increased risk

        These findings persisted even after adjusting for potential confounding factors, including weight variation during the follow-up period[5].

        Impact on Kidney Function

        While the relationship between artificial sweeteners and kidney function is still being studied, some research has raised concerns about their potential negative impact. A notable study revealed a troubling association between diet soda consumption and declining kidney function[3].

        The study found that individuals who consumed more than one diet soda per day experienced a tripling in the rate of kidney function decline compared to those who consumed less or none[3]. This accelerated decline in kidney function could potentially lead to chronic kidney disease (CKD) over time.

        It’s important to note that while this study focused on diet soda, the harmful effects are likely attributed to the artificial sweeteners themselves rather than other components of the soda. This means that adding artificial sweeteners to other beverages like tea, water, or products like Crystal Light could potentially carry similar risks[3].

        Cardiovascular Risks

        The potential cardiovascular risks associated with artificial sweeteners have been a subject of growing concern. A significant study shed light on the increased risk of major adverse cardiovascular events (MACE) and cerebrovascular accidents (CVA) associated with artificial sweetener consumption[10].

        The study, which was part of the large-scale NutriNet-Santé cohort, found that total artificial sweetener intake was associated with increased risk of overall cardiovascular disease (CVD) and cerebrovascular disease. Specifically:

        – Total artificial sweetener intake was associated with a 9% increased risk of cardiovascular diseases and an 18% increased risk of cerebrovascular disease[10].

        – Aspartame consumption was linked to a 17% increased risk of cerebrovascular events[10].

        – Acesulfame potassium and sucralose were associated with a 40% and 31% increased risk of coronary heart disease, respectively[10].

        These findings suggest that substituting artificial sweeteners for added sugar may not confer any cardiovascular benefits. In fact, it may increase the risk of heart-related issues[1].

        Obesity Paradox: How Artificial Sweeteners May Contribute to Weight Gain

        One of the most counterintuitive findings in artificial sweetener research is their potential role in promoting obesity, despite being marketed as a tool for weight loss. Several studies have highlighted this paradoxical effect[8].

        These epidemiological findings are supported by experimental evidence suggesting several potential mechanisms:

        – Artificial sweeteners may lead to sugar cravings and dependence

        – They can impair caloric compensation, resulting in appetite stimulation and increased consumption

        – Some studies indicate that artificial sweeteners may alter gut microbiota, potentially impacting glucose tolerance and metabolism[8]

        Problematic Sweeteners and Their Widespread Use

        While all artificial sweeteners have raised concerns, some appear to be more problematic than others based on current research:

        1. Aspartame: Linked to increased risk of cerebrovascular events and T2D[10][5].

        2. Acesulfame potassium (Ace-K): Associated with increased coronary heart disease risk and T2D[10][5].

        3. Sucralose: Linked to increased coronary heart disease risk and T2D, albeit to a lesser extent than aspartame and Ace-K[10][5].

        It’s crucial to understand that these risks are not limited to diet sodas. Artificial sweeteners are ubiquitous in our food supply, found in low-calorie or sugar-free beverages, “light” yogurts and dairy products, sugar-free candies and gum, baked goods marketed as low-calorie or sugar-free, powdered drink mixes, and some processed foods labeled as “reduced sugar” or “no sugar added”[2].

        Conclusion: A Call for Caution

        The growing body of evidence suggesting potential health risks associated with artificial sweeteners calls for a reevaluation of their widespread use. While they were developed with the intention of providing a healthier alternative to sugar, the long-term consequences of their consumption may outweigh any perceived short-term benefits[9].

        It’s important to note that while individual studies may have limitations, the consistency of findings across multiple large-scale, long-term studies is concerning. The associations between artificial sweetener consumption and increased risks of type 2 diabetes, cardiovascular disease, and potentially obesity and kidney dysfunction warrant serious consideration[1][3][5][10].

        For individuals looking to manage their weight or blood sugar levels, it may be more beneficial to focus on whole, unprocessed foods and to gradually reduce overall sweetener intake, whether artificial or natural. As always, consulting with a healthcare professional for personalized dietary advice is recommended.

        Artificial sweeteners promise a shortcut to health, their names imply “zero” impact on health. These sweeteners, however, are leading us down a dangerous path. Sometimes, the old saying holds true: if it sounds too good to be true, it probably is[2].

        Remember, good health is about making informed choices based on the best available evidence. Stay informed, stay healthy, and think twice before reaching for that artificially sweetened beverage or snack.

        Sources

        [1] Sugar substitutes linked to heart disease, stroke risk – UCI Health https://www.ucihealth.org/blog/2022/09/sugar-substitutes-may-boost-heart-disease-stroke-risk

        [2] Is aspartame safe? Artificial sweeteners landscape – CAS.org https://www.cas.org/resources/cas-insights/aspartame-safe-landscape-artificial-sweeteners-and-sugar

        [3] Sweetened Beverage Intake and Incident Chronic Kidney Disease https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2815563

        [4] Artificial sweeteners and their implications in diabetes: a review https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1411560/full

        [5] Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective … https://pubmed.ncbi.nlm.nih.gov/37490630/

        [6] Associations of artificial sweetener intake with cardiometabolic … https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/associations-of-artificial-sweetener-intake-with-cardiometabolic-disorders-and-mortality-a-populationbased-study/56F1A251916E8C55AA8E23AE653627D5

        [7] Linking artificial sweetener intake with kidney function: insights from … https://pmc.ncbi.nlm.nih.gov/articles/PMC11169671/

        [8] The Association Between Artificial Sweeteners and Obesity – PubMed https://pubmed.ncbi.nlm.nih.gov/29159583/

        [9] Sugar substitutes: New cardiovascular concerns? – Harvard Health https://www.health.harvard.edu/heart-health/sugar-substitutes-new-cardiovascular-concerns

        [10] Artificial sweeteners and risk of cardiovascular diseases – PubMed https://pubmed.ncbi.nlm.nih.gov/36638072/

      4. Bacopa monnieri: A Promising Herb for Cognitive Enhancement

        Bacopa monnieri: A Promising Herb for Cognitive Enhancement

        In the realm of cognitive health supplements, Bacopa monnieri stands out as a herb with a rich history and growing scientific backing. This ancient Ayurvedic medicine, also known as Brahmi, has been used for centuries to enhance memory and cognitive function. Today’s post will briefly describe the research surrounding Bacopa monnieri and its potential impact on cognitive dysfunction.

        The Science Behind Bacopa monnieri

        Physiological Effects and Pharmacology

        Bacopa monnieri contains several active compounds, primarily triterpenoid saponins called bacosides. These compounds are believed to be responsible for the herb’s cognitive-enhancing effects[1]. Research suggests that Bacopa monnieri works through multiple mechanisms:

        1. Neurotransmitter Modulation: Bacopa may influence the synthesis and availability of neurotransmitters, particularly serotonin, which plays a crucial role in mood regulation and cognitive function[1].
        2. Neuroprotection: The herb exhibits antioxidant properties, potentially protecting neurons from oxidative stress and damage[5].
        3. Synaptic Plasticity: Bacopa monnieri has been shown to enhance synaptic function, which is crucial for learning and memory[2].
        4. Amyloid Reduction: Studies indicate that Bacopa may reduce the accumulation of beta-amyloid, a protein associated with Alzheimer’s disease[5].

        Clinical Evidence

        Several clinical trials have investigated the effects of Bacopa monnieri on cognitive function:

        • A 12-week, double-blind, placebo-controlled study in adults over 55 years old found that Bacopa significantly improved memory acquisition and retention[1].
        • Another study involving 76 adults aged 40-65 demonstrated that Bacopa enhanced the retention of new information, suggesting it may decrease the rate of forgetting newly acquired data[8].
        • Research has also shown potential benefits in attention, cognitive processing, and working memory, partly through the suppression of acetylcholinesterase activity[3].

        Contrasting with Non-Evidence Based Supplements

        While Bacopa monnieri shows promise, it’s essential to contrast it with other brain health supplements on the market that lack solid scientific backing. For instance, a widely advertised supplement (which shall remain unnamed) has faced legal action from the Federal Trade Commission (FTC) for making unsubstantiated claims about improving memory and cognitive function[11].

        The FTC and New York State Attorney General charged the marketers of this supplement with false advertising, alleging that their extensive national campaign, featuring charts depicting rapid and dramatic memory improvement, was not supported by reliable scientific evidence[11].

        This case highlights the importance of scrutinizing claims made by supplement manufacturers. Unlike the rigorous clinical trials conducted on Bacopa monnieri, some products rely on poorly designed studies or make claims that far exceed the available evidence.

        Implications for Cognitive Health

        The growing body of research on Bacopa monnieri suggests it may be a valuable tool in addressing cognitive dysfunction. Its potential to enhance memory, reduce anxiety, and protect against neurodegenerative processes makes it an intriguing option for those seeking to support their cognitive health[5].

        However, it’s crucial to approach all supplements with a critical eye. While Bacopa monnieri has a more substantial evidence base than many other “brain-boosting” supplements, more research is still needed to fully understand its long-term effects and optimal dosing.

        Conclusion

        Bacopa monnieri represents a promising natural approach to cognitive enhancement, backed by centuries of traditional use and a growing body of scientific evidence. As research continues, it may prove to be a valuable tool in the fight against cognitive decline and neurodegenerative diseases.

        However, consumers should remain cautious of supplements making grandiose claims without solid scientific backing. Always consult with a healthcare professional before starting any new supplement regimen, and remember that a healthy lifestyle, including regular exercise, a balanced diet, and adequate sleep, remains the foundation of good cognitive health.

        By staying informed and critically evaluating the claims of various brain health products, we can make better decisions about our cognitive well-being and potentially benefit from evidence-based natural supplements like Bacopa monnieri.

        Sources
        [1] Effects of a Standardized Bacopa monnieri Extract on Cognitive … https://pmc.ncbi.nlm.nih.gov/articles/PMC3153866/
        [2] Bacopa monnieri Extract As a Neuroprotective and Cognitive … https://www.sciltp.com/journals/ijddp/2023/4/315
        [3] Effects of 12‐Week Bacopa monnieri Consumption on Attention … https://onlinelibrary.wiley.com/doi/10.1155/2012/606424
        [4] [PDF] A Review of Evidence of Brahmi (Bacopa monniera) – Frontiers https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00044/pdf
        [5] The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic … https://www.nature.com/articles/s41598-020-80045-2
        [6] A Public Health Issue: Dietary Supplements Promoted for Brain … https://pmc.ncbi.nlm.nih.gov/articles/PMC7153641/
        [7] Court ruling curbs unfounded claims for memory supplement https://www.health.harvard.edu/blog/court-ruling-curbs-unfounded-claims-for-memory-supplement-201905311887
        [8] Chronic Effects of Brahmi (Bacopa monnieri) on Human Memory https://www.nature.com/articles/1395862
        [9] Pharmacological attributes of Bacopa monnieri extract https://pmc.ncbi.nlm.nih.gov/articles/PMC9436272/
        [10] Don’t buy into brain health supplements – Harvard Health https://www.health.harvard.edu/mind-and-mood/dont-buy-into-brain-health-supplements
        [11] FTC, New York State Charge the Marketers of Prevagen With … https://www.ftc.gov/news-events/news/press-releases/2017/01/ftc-new-york-state-charge-marketers-prevagen-making-deceptive-memory-cognitive-improvement-claims

      5. Preventing Diabetes

        Preventing Diabetes

        Diabetes Prevention Program (DPP) and Follow-up Studies

        Frequently in our practice, we discuss with our patients, who often have a strong family history of diabetes mellitus or have evidence of pre-diabetes, interventions that have been shown to help forestall diabetes. In these conversations we often quote the Diabetes Prevention Program trial. The Diabetes Prevention Program (DPP) was a landmark clinical trial that demonstrated the effectiveness of lifestyle intervention and pharmacological therapy in preventing or delaying the onset of type 2 diabetes in high-risk individuals. Below is an overview of the DPP and subsequent studies:

        Original DPP Trial (1996-2001)

        The DPP was a 27-center randomized clinical trial involving 3,234 participants with impaired glucose tolerance[10], a marker of a propensity toward diabetes. The study compared three interventions:

        1. Intensive lifestyle intervention

        2. Metformin therapy

        3. Placebo

        Key Results:

        – Lifestyle intervention reduced diabetes incidence by an impressive 58% compared to placebo[1][10].

        – Metformin is an inexpensive medication discovered in 1922. Metformin is derived from the lilac tree and has been used as a natural intervention since the Middle Ages. Metformin reduced diabetes incidence by 31% compared to placebo[1][10].

        – The lifestyle intervention was particularly effective in adults aged 60 and older, reducing diabetes risk by 71%[1].

        Intervention Details:

        – Lifestyle group: Aimed for 7% weight loss and 150 minutes of physical activity per week[1].

        – Metformin group: 850 mg twice daily[1].

        Diabetes Prevention Program Outcomes Study (DPPOS)

        The DPPOS is a long-term follow-up of the original DPP participants.

        10-Year Follow-up Results:

        – Lifestyle intervention group: 34% reduction in diabetes development[1].

        – Metformin group: 18% reduction in diabetes development[1].

        15-Year Follow-up Results:

        – Lifestyle intervention group: 27% reduction in diabetes development[1].

        – Metformin group: 18% reduction in diabetes development[1].

        21-Year Follow-up Results:

        – Persistent reductions in type 2 diabetes development were observed over an average 22-year follow-up period[11].

        Cost-Effectiveness

        – The DPP Lifestyle Change Program was found to be cost-effective after 10 years[1].

        – Metformin was cost-saving, leading to small savings in healthcare costs[1].

        Other Significant Trials and Studies

        Indian Diabetes Prevention Programme

        This study demonstrated that lifestyle modification and metformin could reduce the incidence of diabetes in Asian Indian subjects with impaired glucose tolerance[3].

        PREDIMED Trial

        A Mediterranean diet supplemented with nuts or extra virgin olive oil was shown to help prevent type 2 diabetes compared to a control diet, even without weight loss[3].

        Studies on High-Risk Populations

        Pima Indians

        – Arizona Pimas had a 38% prevalence of type 2 diabetes[6].

        – Mexican Pimas had only a 6.9% prevalence, similar to non-Pima Mexicans (2.6%)[6].

        South Asians

        – Age-adjusted prevalence of diabetes: 23% in South Asians compared to 6% in whites, 18% in African Americans, 17% in Latinos, and 13% in Chinese Americans[8].

        Hispanic Population

        – 19.8% total diabetes prevalence among Hispanics compared to 12.4% in non-Hispanic whites[9].

        American Indian and Alaska Native Population

        – Almost 3 times more likely to have type 2 diabetes compared to White adults[12].

        – Diagnosed diabetes more than doubled among Native adults 35 or younger from 1994 to 2004[12].

        Pharmacological Interventions in Children

        A study of 26 obese children with type 2 diabetes showed:

        – 16 were initially treated with metformin

        – 4 with sulfonylurea

        – 2 with α-glucosidase inhibitor

        – 4 received insulin[5]

        Conclusion

        The DPP and subsequent studies have consistently shown that lifestyle interventions and metformin can significantly reduce the risk of developing type 2 diabetes in high-risk individuals. These interventions have proven effective across various populations, including those with higher genetic predisposition to diabetes. Long-term follow-up studies continue to demonstrate the lasting benefits of early intervention in diabetes prevention.

        Sources

        [1] Diabetes Prevention Program (DPP) – NIDDK https://www.niddk.nih.gov/about-niddk/research-areas/diabetes/diabetes-prevention-program-dpp?dkrd=prspt1922

        [2] Evidence – National DPP Coverage Toolkit https://coveragetoolkit.org/about-national-dpp/evidence/

        [3] Dietary Interventions for the Prevention of Type 2 Diabetes in High … https://pmc.ncbi.nlm.nih.gov/articles/PMC6163866/

        [4] ACSM Publishes New Recommendations on Type 2 Diabetes and … https://www.acsm.org/news-detail/2022/02/09/acsm-publishes-new-recommendations-on-type-2-diabetes-and-exercise

        [5] Pharmacologic Treatment Strategies in Children with Type 2 … https://pmc.ncbi.nlm.nih.gov/articles/PMC3748280/

        [6] High-Risk Populations: The Pimas of Arizona and Mexico – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC4418458/

        [7] New study shows decrease in diabetes prevalence for American … https://www.ihs.gov/newsroom/ihs-blog/april-2020-blogs/new-study-shows-decrease-in-diabetes-prevalence-for-american-indian-and-alaska-native-adults/

        [8] Understanding the High Prevalence of Diabetes in U.S. South … https://pmc.ncbi.nlm.nih.gov/articles/PMC4030091/

        [9] Innovative Diabetes Interventions in the U.S. Hispanic Population https://diabetesjournals.org/spectrum/article/32/4/295/32396/Innovative-Diabetes-Interventions-in-the-U-S

        [10] The Diabetes Prevention Program (DPP) – PubMed Central https://pmc.ncbi.nlm.nih.gov/articles/PMC1282458/

        [11] DPP Continues to Yield Positive Results, New DPPOS Data Show https://www.ajmc.com/view/dpp-continues-to-yield-positive-results-new-dppos-data-show

        [12] Improving Health in Indian Country | Diabetes – CDC https://www.cdc.gov/diabetes/health-equity/health-american-indian.html

      6. Exercise mimetics: A substitute for exercise?

        With our increasingly busy lives, the idea of taking a pill to get the benefits of exercise sounds like a dream come true. But can these so-called “exercise mimetics” really replace our gym sessions? Let’s dive into the science behind these compounds and see how they stack up against good old-fashioned sweat.

        What Are Exercise Mimetics?

        Exercise mimetics are substances that aim to replicate some of the beneficial effects of physical activity at a cellular level. While they show promise in certain areas, it’s crucial to understand that they’re not magic bullets. Here are ten compounds that have caught researchers’ attention:

        1. AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide): This AMPK activator has been shown to increase endurance in mice by 44% and improve insulin sensitivity.

        2. GW501516 (Cardarine): A PPARδ agonist that increased running time in mice by 68% and improved lipid profiles in humans.

        3. Resveratrol: Found in red wine, this compound doubled the running distance of mice on a high-fat diet and improved mitochondrial function in humans.

        4. Metformin: An anti-diabetic drug that increases AMPK activity in skeletal muscle, similar to endurance exercise.

        5. SRT1720: A SIRT1 activator that increased exercise endurance in mice by 44% and protected against diet-induced obesity.

        6. GSK4716: An ERRγ agonist that improved exercise performance in mice by 22% and enhanced fatty acid metabolism.

        7. Irisin: A myokine released during exercise that increases energy expenditure and improves glucose homeostasis.

        8. β-aminoisobutyric acid (BAIBA): Another exercise-induced myokine that promotes fat burning and is associated with lower cardiometabolic risk.

        9. Compound 14: An AMPK activator that improved glucose uptake and reduced body weight in obese mice.

        10. Eugenol: Found in clove oil, this compound improved exercise endurance in mice by 20% and promoted muscle fiber transformation.

        The Reality Check: Exercise Still Reigns Supreme

        While these compounds show promise, they’re not a substitute for the real deal. Here’s why exercise is still king:

        1. Heart Health: Regular exercise reduces cardiovascular mortality risk by 35% and all-cause mortality by 33%.

        2. Metabolic Health: Exercise interventions can reduce HbA1c by 0.8% in type 2 diabetics, a significant clinical improvement.

        3. Bone and Muscle Health: Physical activity can reduce hip fracture risk by up to 68% in postmenopausal women.

        4. Brain Power: Regular exercise can lower the risk of cognitive decline by 38%.

        5. Mental Wellbeing: Physical activity reduces the odds of developing depression by 17%.

        The Numbers Don’t Lie

        Let’s look at some hard data on how exercise impacts various health conditions:

        Cardiovascular Disease: High levels of physical activity (>750 minutes per week) are associated with a 35% reduction in mortality risk and a 25% reduction in major cardiovascular events.

        – Type 2 Diabetes: High levels of physical activity are linked to a 26% lower risk of developing type 2 diabetes.- Cancer*: Regular exercise is associated with lower risks of 13 types of cancer, with risk reductions ranging from 10% for breast cancer to 42% for esophageal adenocarcinoma.

        – All-Cause Mortality: Just 15 minutes of moderate-intensity exercise daily can reduce all-cause mortality risk by 14% and increase life expectancy by 3 years.

        – Neurodegenerative Diseases: Physical activity is associated with a 28% lower risk of dementia and a 45% lower risk of Alzheimer’s disease.

        The Bottom Line

        While exercise mimetics are an exciting area of research, they’re not a replacement for physical activity. The comprehensive benefits of exercise on cardiovascular health, metabolism, musculoskeletal system, cognitive function, and mental health simply can’t be replicated in a pill.

        So, while these compounds might have potential therapeutic applications, especially for those unable to exercise, they shouldn’t be seen as a substitute for regular physical activity. The best “pill” for overall health and longevity? It’s still exercise.

        References

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        2. Sprecher DL, et al. Arterioscler Thromb Vasc Biol. 2007;27(2):359-365.

        3. Lagouge M, et al. Cell. 2006;127(6):1109-1122.

        4. Timmers S, et al. Cell Metab. 2011;14(5):612-622.

        5. Musi N, et al. Diabetes. 2002;51(7):2074-2081.

        6. Feige JN, et al. Cell Metab. 2008;8(5):347-358.

        7. Narkar VA, et al. Cell Metab. 2011;13(3):283-293.

        8. Boström P, et al. Nature. 2012;481(7382):463-468.

        9. Roberts LD, et al. Cell Metab. 2014;19(1):96-108.

        10. Gómez-Galeno JE, et al. J Med Chem. 2010;53(16):6198-6208.

        11. Li Y, et al. J Agric Food Chem. 2023;71(5):2392-2402.

        12. Nystoriak MA, Bhatnagar A. Compr Physiol. 2018;8(2):765-792.

        13. Snowling NJ, Hopkins WG. Diabetologia. 2006;49(11):2254-2266.

        14. Warburton DE, et al. CMAJ. 2006;174(6):801-809.

        15. Sofi F, et al. J Intern Med. 2011;269(1):107-117.

        16. Schuch FB, et al. Am J Psychiatry. 2018;175(7):631-648.

        17. Lear SA, et al. Lancet. 2017;390(10113):2643-2654.

        18. Aune D, et al. Diabetologia. 2015;58(7):1474-1487.

        19. Moore SC, et al. JAMA Intern Med. 2016;176(6):816-825.

        20. Wen CP, et al. Lancet. 2011;378(9798):1244-1253.

        21. Hamer M, Chida Y. Psychol Med. 2009;39(1):3-11.