Category Archives: Longevity

Finerenon: New Hope for Prevention of Kidney Disease and Cardiac Death in Type 2 Diabetes

Your friendly neighborhood drug supplier

Verbatim from the FDA press release:

FDA has approved Kerendia (finerenone) tablets to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.

Diabetes is the leading cause of chronic kidney disease and kidney failure in the United States. Chronic kidney disease occurs when the kidneys are damaged and cannot filter blood normally. Because of defective filtering, patients can have complications related to fluid, electrolytes (minerals required for many bodily processes), and waste build-up in the body. Chronic kidney disease sometimes can progress to kidney failure. Patients also are at high risk of heart disease.

The ultimate role of finerenone in our armamentarium against disease and suffering will probably depend on cost and the number needed to treat.

The efficacy of Kerendia to improve kidney and heart outcomes was evaluated in a randomized, multicenter, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes. In this study, 5,674 patients were randomly assigned to receive either Kerendia or a placebo.

The study compared the two groups for the number of patients whose disease progressed to a composite (or combined) endpoint that included at least a 40% reduction in kidney function, progression to kidney failure, or kidney death. Results showed that 504 of the 2,833 patients who received Kerendia had at least one of the events in the composite endpoint compared to 600 of the 2,841 patients who received a placebo.

The study also compared the two groups for the number of patients who experienced cardiovascular death, a non-fatal heart attack, non-fatal stroke, or hospitalization for heart failure. Results showed that 367 of the 2,833 patients receiving Kerendia had at least one of the events in the composite endpoint compared to 420 of the 2,841 patients who received a placebo, with the treatment showing a reduction in the risk of cardiovascular death, non-fatal heart attack, and hospitalization for heart failure.

Side effects of Kerendia include hyperkalemia (high levels of potassium), hypotension (low blood pressure), and hyponatremia (low levels of sodium). Patients with adrenal insufficiency (when the body does not produce enough of certain hormones) and those receiving simultaneous treatment with strong CYP3A4 inhibitors should not take Kerendia.

Kerendia received priority review and fast track designations for this application.

FDA granted the approval of Kerendia to Bayer Healthcare.


Click for prescribing information.


Parker here.

Just offhand, finerenone doesn’t look like a great drug. Helpful, maybe. Chronic kidney disease can end up at ESRD (end stage renal disease), which requires thrice weekly hemodialysis if the patient wants to stay alive. (Yes, peritoneal dialysis is an alternative.) Preventing ESRD is an incredible benefit for an individual.

Finerenone seems to be a well-tolerated daily pill. The main adverse effect is elevated blood potassium level, which can cause palpitations, and death infrequently. Less commonly, the drug can cause low blood pressure.

Steve Parker, M.D.

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Filed under Drugs for Diabetes, Heart Disease, kidney disease, Longevity, Stroke

High Glycemic Index Eating Linked to Higher Risk of Cardiovascular Disease and Death

Haven’t we known this for years? Click for definition and discussion of glycemic index and glycemic load.

“One little piece won’t hurt . . .”

From New England Journal of Medicine:

Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population.

METHODS

This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause.

RESULTS

In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease.

CONCLUSIONS

In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death.

Source: Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality | NEJM

The low-carb Mediterranean diet is low glycemic index.

Steve Parker, M.D.

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Filed under coronary heart disease, Heart Disease, Longevity

Don’t Let Aging Reduce Your Muscle Mass

Exercise is a fountain of youth available to every one

Axel Sigurdsson, MD, PhD, published a great article on prevention of age-related sarcopenia (loss of muscle mass). Click through for details. To stay vigorous as you age, you want to preserve muscle mass and the strength it provides. If you’ve lost muscle mass, you can re-build it. Summary from the good doctor:

Age-related loss of muscle mass (sarcopenia)may start as early as in our thirties and appears to continue for the rest of our lives.

There is also a loss of muscle strength and muscle function. The consequences may often be severe, particularly in the elderly.

Increased physical activity and adequate nutrition are the most powerful tools at our disposal to delay age-related loss of muscle mass.

Well-rounded exercise programs consisting of aerobic and resistance exercises are believed to be most effective

Modification of dietary habits may be an important tool to prevent the decline in muscle mass and function that occurs with aging.

Adequate protein intake is of key importance. Animal-derived protein may provide a higher and broader biological value than vegetable protein.

Fish consumption is recommended and fruits and vegetables should be consumed regularly.

Nutritional supplements containing essential amino acids may be helpful. This is particularly true for whey protein.

Fish-derived protein hydrolysates also appear promising.

Adequate intake of vitamin D is essential.

“Fish-derived protein hydrolysates” doesn’t sound very appetizing. I’ll stick with whole fish for now, especially cold-water fatty fish.

Steve Parker, M.D.

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Filed under Exercise, Longevity

Mediterranean Diet Linked to Reduced Frailty in the Elderly

Cold-water fatty fish loaded with omega-3 fatty acids include salmon, trout, sardines, herring, and mackerel

In the study at hand, frailty was measured by exhaustion, weakness, physical activity, walking speed, and weight loss. From the Journal of the American Medical Medical Directors Association way back in 2014:

Abstract

Background and objective: Low intake of certain micronutrients and protein has been associated with higher risk of frailty. However, very few studies have assessed the effect of global dietary patterns on frailty. This study examined the association between adherence to the Mediterranean diet (MD) and the risk of frailty in older adults.

Design, setting, and participants: Prospective cohort study with 1815 community-dwelling individuals aged ≥60 years recruited in 2008-2010 in Spain.

Measurements: At baseline, the degree of MD [Mediterranean Diet] adherence was measured with the Mediterranean Diet Adherence Screener (MEDAS) score and the Mediterranean Diet Score, also known as the Trichopoulou index. In 2012, individuals were reassessed to detect incident frailty, defined as having at least 3 of the following criteria: exhaustion, muscle weakness, low physical activity, slow walking speed, and weight loss. The study associations were summarized with odds ratios (OR) and their 95% confidence interval (CI) obtained from logistic regression, with adjustment for the main confounders.

Results: Over a mean follow-up of 3.5 years, 137 persons with incident frailty were identified. Compared with individuals in the lowest tertile of the MEDAS score (lowest MD adherence), the OR (95% CI) of frailty was 0.85 (0.54-1.36) in those in the second tertile, and 0.65 (0.40-1.04; P for trend = .07) in the third tertile. Corresponding figures for the Mediterranean Diet Score were 0.59 (0.37-0.95) and 0.48 (0.30-0.77; P for trend = .002). Being in the highest tertile of MEDAS was associated with reduced risk of slow walking (OR 0.53; 95% CI 0.35-0.79) and of weight loss (OR 0.53; 95% CI 0.36-0.80). Lastly, the risk of frailty was inversely associated with consumption of fish (OR 0.66; 95% CI 0.45-0.97) and fruit (OR 0.59; 95% CI 0.39-0.91).

Conclusions: Among community-dwelling older adults, an increasing adherence to the MD was associated with decreasing risk of frailty.

Did you notice another good reason to eat fish?

I wonder why the research was published in the Journal of the American Medical Medical Directors Association?

Steve Parker, M.D.

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Filed under Fish, Health Benefits, Longevity, Mediterranean Diet

Mediterranean Diet Benefits Elderly Hospitalized Patients

…at least in Greece, where the study was done.

Not sure where this is. Leave a comment if you recognize it.

The Mediterranean diet in an observational study of folks over 65 admitted to a hospital was linked to:

  • Shorter duration of hospitalization
  • Reduced healthcare cost
  • Improved longevity

The study at hand lasted two years.

Abstract

Objective:

Mediterranean diet (MD) has been related to reduced overall mortality and improved diseases’ outcome. Purpose of our study was to estimate the impact of MD on duration of admission, financial cost and mortality (from hospitalization up to 24 months afterwards) in elderly, hospitalized patients.

Research Methods & Procedures:

One hundred eighty three elderly patients (aged >65 years), urgently admitted for any cause in the Internal Medicine department of our hospital, participated in this observational study. Duration of admission and its financial cost, mortality (during hospitalization, 6 and 24 months after discharge), physical activity, medical and anthropometric data were recorded and they were correlated with the level of adherence to MD (MedDiet score).

Results:

In multivariate analyses, duration of admission decreased 0.3 days for each unit increase of MedDiet score (p<0.0001), 2.1 days for each 1g/dL increase of albumin (p=0.001) and increased 0.1 days for each day of previous admissions (p<0.0001). Extended hospitalization (p<0.0001) and its interaction with MedDiet score (p=0.01) remained the significant associated variables for financial cost. Mortality risk increased 3% per each year increase of age (HR=1.03, p=0.02), 6% for each previous admission (HR=1.06, p=0.04) whereas it decreased 13% per each unit increase of MedDiet score (HR=0.87, p<0.0001).

Conclusion:

Adoption of MD decreases duration of admission and long-term mortality in elderly hospitalized patients with parallel reduction of relevant financial cost.

Source: The impact of Mediterranean Diet on duration of admission, medical expenses and mortality in elderly, hospitalized patients: A 2-year observational study – ScienceDirect

I haven’t read the entire article. Didn’t see any need, based on my prior knowledge of the Mediterranean diet. The findings are not unexpected.

Steve Parker, M.D.

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Low-Carb Diets Improve Cardiovascular Risk Factors

This Avocado Chicken soup is very low-carb. Use the search box to find the recipe.

A meta-analysis by Chinese investigators found that low-carb diets improve cardiovascular risk factors. Specifically: body weight (lowered), triglycerides (lowered), HDL-cholesterol (raised), blood pressure (lowered systolic and diastolic, but less than 2 points each).

Additionally, they found increases in total cholesterol  and HDL-cholesterol. Some consider those to be going in the wrong direction, increasing cardiovascular risk. The study authors, however, considered these increases “slight,” implying lack of real-world significance.

I’ll not fisk the entire research paper. Have a go at it yourself by clicking the link to full-text below.

The researchers included 12 randomized controlled trials in their analysis. They defined low-carb diets as having less than 40% of calories derived from carbohydrates. If you’re eating 2200 calories a day, 39% of calories from carb would be 215 g of carbs/day. That’s a lot of carb, and wouldn’t be much lower than average. I scanned the report pretty quickly and didn’t run across an overall average for carb grams or calories in the low-carb diets. The “control diets” had 45–55% of calories from carbohydrate.

Here’s the abstract:

Background

Low-carbohydrate diets are associated with cardiovascular risk factors; however, the results of different studies are inconsistent.

Purpose

The aim of this meta-analysis was to assess the relationship between low-carbohydrate diets and cardiovascular risk factors.

Method

Four electronic databases (PubMed, Embase, Medline, and the Cochrane Library) were searched from their inception to November 2018. We collected data from 12 randomized trials on low-carbohydrate diets including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, and blood pressure levels, as well as weight as the endpoints. The average difference (MD) was used as the index to measure the effect of a low-carbohydrate diet on cardiovascular risk factors with a fixed-effects model or random-effects model. The analysis was further stratified by factors that might affect the results of the intervention.

Results

From 1292 studies identified in the initial search results, 12 randomized studies were included in the final analysis, which showed that a low-carbohydrate diet was associated with a decrease in triglyceride levels of -0.15mmol/l (95% confidence interval -0.23 to -0.07). Low-carbohydrate diet interventions lasting less than 6 months were associated with a decrease of -0.23mmol/l (95% confidence interval -0.32 to -0.15), while those lasting 12–23 months were associated with a decrease of -0.17mmol/l (95% confidence interval -0.32 to -0.01). The change in the body weight in the observation groups was -1.58kg (95% confidence interval -1.58 to -0.75); with for less than 6 months of intervention, this change was -1.14 kg (95% confidence interval -1.65 to -0.63),and with for 6–11 months of intervention, this change was -1.73kg (95% confidence interval -2.7 to -0.76). The change in the systolic blood pressure of the observation group was -1.41mmHg (95% confidence interval—2.26 to -0.56); the change in diastolic blood pressure was -1.71mmHg (95% confidence interval—2.36 to -1.06); the change in plasma HDL-C levels was 0.1mmHg (95% confidence interval 0.08 to 0.12); and the change in serum total cholesterol was 0.13mmol/l (95% confidence interval 0.08 to 0.19). The plasma LDL-C level increased by 0.11mmol/l (95% confidence interval 0.02 to 0.19), and the fasting blood glucose level changed 0.03mmol/l (95% confidence interval -0.05 to 0.12),which was not significant.

Conclusions

This meta-analysis confirms that low-carbohydrate diets have a beneficial effect on cardiovascular risk factors but that the long-term effects on cardiovascular risk factors require further research.

Source: The effects of low-carbohydrate diets on cardiovascular risk factors: A meta-analysis

Steve Parker, M.D.

PS: You know what else reduces cardiovascular disease risk? The Mediterranean diet. The Diabetic Mediterranean Diet provides between 20 and 100 grams of digestible carb daily, depending on your individual carbohydrate tolerance level.

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Tea in China Prolongs Life and Prevents Heart Disease

One of my favorite green teas

For years we’ve been hearing about the potential longevity and cardiovascular benefits of green tea. If memory serves, most of the data comes from Japanese studies. Now a Chinese observational study finds 15–20% reductions in atherosclerotic cardiovascular disease (ASCVD) and death, compared to non-tea drinkers. Most of the participants drank green tea, and they did so at least thrice weekly.

From the European Journal of Preventive Cardiology:

Using large prospective cohorts among general Chinese adults, we have provided novel evidence on the protective role of tea consumption on ASCVD events and all-cause mortality, especially among those who kept the habit all along. The current study indicates that tea might be a healthy beverage for primary prevention against ASCVD and premature death.

Source: Tea consumption and the risk of atherosclerotic cardiovascular disease and all-cause mortality: The China-PAR project – Xinyan Wang, Fangchao Liu, Jianxin Li, Xueli Yang, Jichun Chen, Jie Cao, Xigui Wu, Xiangfeng Lu, Jianfeng Huang, Ying Li, Liancheng Zhao, Chong Shen, Dongsheng Hu, Ling Yu, Xiaoqing Liu, Xianping Wu, Shouling Wu, Dongfeng Gu,

The researchers point out that results may not apply to non-Chinese populations.

Steve Parker, M.D.

h/t to Jan at The Low Carb Diabetic (click link for more details about the study)

low-carb mediterranean diet

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Mediterranean Diet Wins #1 Rank Once Again #MediterraneanDiet

Santorini, Greek seaside

Not surprising!

Every year, the U.S. News and World Report puts together a panel of experts to rank various diets.

From MedScape:

For the third year in a row, the Mediterranean diet has been named the best diet overall in the U.S. News & World Report annual rankings.

In 2018, the Mediterranean diet shared top honors with the DASH (Dietary Approaches to Stop Hypertension) diet. Both focus on fruits, vegetables, and whole grains. The ketogenic diet, one of the most popular, again fared well in the annual survey, but only in the fast weight loss category. Overall, it was not rated highly.

Angela Haupt, managing editor of health for the publication, says this year’s list has ”no surprises,” as it includes many diets that have been named outstanding before. Trendy diets typically won’t be found on its list, she says, explaining that its experts look for plans that have solid research and staying power.

Source: Mediterranean Diet Repeats as Best Overall of 2020

Steve Parker, M.D.

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Fasting: Not Ready for Prime Time?

This caveman probably went days without food, and often

Dr Axel Sigurdsson published an epic post on intermittent fasting early in 2020. I don’t doubt anything in it although I haven’t yet taken a deep dive into the subject like he has. I touched on it here, here, here, and here. I’ve done some 24-hour fasting myself (here and here).

From the good doctor:

Animal studies suggest that intermittent fasting may have several health benefits. Some of these benefits, in particular, the effects on obesity, type 2 diabetes, and cardiovascular risk factors, have been confirmed in studies on humans.

However, the popularity of intermittent fasting within the general public is in stark contrast with the gaps in evidence on the clinical benefits of this approach.

Source: Intermittent Fasting and Health – The Scientific Evidence

Steve Parker, M.D.

PS: PWDs taking drugs that can cause hypoglycemia would have to be extremely careful about fasting, working with their doctors or CDEs.

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Alarming Rise In Suicides Among Young Americans

This too shall pass

From The New York Times:

After declining for nearly two decades, the suicide rate among Americans ages 10 to 24 jumped 56 percent between 2007 and 2017, according to data from the Centers for Disease Control and Prevention. And for the first time the gender gap in suicide has narrowed: Though the numbers of suicides are greater in males, the rates of suicide for female youths increased by 12.7 percent each year, compared with 7.1 percent for male youths.

If you or someone you know needs help dealing with suicidal thought, please please please contact the National Suicide Prevention Lifeline at 1-800-273-8255.

Steve Parker, M.D.

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