…according to an article at Annals of Internal Medicine. The study was done in a U.K. population over decade of observation. The 10% or more reduction in all-cause mortality was seen at a habitual consumption level of two or more cups of black tea daily. Most prior similar studies I’ve seen focus on green tea.
Question What were the long-term findings of Age-Related Eye Disease Study 2 (AREDS2) supplements regarding development of lung cancer or progression to late age-related macular degeneration (AMD)?
Findings In this epidemiologic follow-up study of the AREDS2 cohort of 3882 participants and 6351 eyes, 10-year follow-up results showed that development of lung cancer nearly doubled in participants assigned to beta carotene among former smokers but not those assigned to lutein/zeaxanthin. Lutein/zeaxanthin was associated with a reduction in the risk of progression to late AMD when compared with beta carotene.
Meaning These findings suggest that the AREDS2 supplement with lutein/zeaxanthin instead of beta carotene was safe, with no association with developing lung cancer and a potential beneficial association with further reduction in progression to late AMD.
Nutritional discipline and dietary restriction result in resistance exercise for our cells. Triggered by calorie restriction or physical exercise, our cells end up producing transcription factors that lead to protection against oxidation, inflammation, atherosclerosis, and carcinogenic proliferation. In the long-term, this results in longevity and a decrease in cancer, T2DM [type 2 diabetes], myocardial infarction, and stroke. Since centuries past, studies on humans, rhesus monkeys, and multilevel organisms have demonstrated the benefits of calorie restriction without malnutrition. Periodic fasting and calorie restriction show increases in regeneration markers and decreases in biomarkers for diabetes, CVD [cardiovascular disease], cancer, and aging.
The present review concluded that longevity can be increased through moderation of diet and exercise. Research shows that a concoction of the diverse diets modernly popularized— MED [Mediterranean], DASH, high-protein diets±—tempered by overall calorie restriction through periodic fasting or chronic calorie restriction, will provide protection against CVD, cancer, and aging. Exercise has also been shown to increase longevity in the general population, lower incidence of diabetes and cancer, and produce psychological benefits.
This review of research indicates that incorporating a moderate caloric restriction or fasting regimen could provide substantial benefits at low risk. Cellular exercise through calorie restriction and physical exercise can increase longevity and prevent the greatest killers of human society today—stroke and heart disease.
Proton Pump Inhibitor drugs (PPIs) greatly reduce the production of acid in the stomach. They revolutionized and improved the treatment of ulcers in the stomach and duodenum. When I started medical practice in 1981, I saw many patients who had required stomach surgery to treat their ulcers. Remember the good ol’ Billroth procedures? Of course you don’t. The first PPI approved for use in the US. was cimetidine (Tagamet) in 1979.
But wait, you say. “Isn’t there a reason we have stomach acid in the first place?” Good question! Because if we reduce stomach acid, it may cause problems. Regardless of what acid contributes to food digestion, it also kills germs in food and water. Germs that may kill us if ignored. Most of us in the developed world would be horrified to drink untreated water out of a lake, stream, river, or spring. But what do you think Homo sapiens did for most our 200,000 years of our existence?
Omeprazole was made over the counter in 2003 but I don’t think these drugs should ever have been made available without prescription. PPIs are powerful drugs that treat heartburn by reducing gastric acid production. This is accomplished by PPI binding to the hydrogen/potassium ATPase enzyme on gastric parietal cells lining the stomach. PPIs do more than block acid. They are associated with an increased risk of congestive heart failure, kidney disease, long bone fractures, and dementia, vitamin B12 deficiency, reviewed here. Regular use of proton pump inhibitors is associated with increased incidence of type two diabetes, about 24% higher compared to non-users of the drug. Proton pump inhibitors are also linked an with increased risk of small intestinal bacterial overgrowth (which is a clue as to why these drugs can be harmful). They also increase the risk of infection by Clostridiales difficile by about 2x.
Most of these individual observational studies are unable to establish causation, but the preponderance of evidence points to PPIs causing harm.
Dr Alcock also found evidence that PPI users who catch COVID-19 have 1.6x increased risk for severe disease and death.
If you’re prescribed a PPI for chronic use, check with your physician to see if you still need it. Occasional use for heartburn shouldn’t be a problem. For chronic heartburn, consider a low-carb diet and stop nocturnal alcohol consumption.
Haven’t we know this for years? 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.
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.
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.
In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death.
A recent study looked at the health benefits of type 2 diabetes drugs, comparing drugs that can cause hypoglycemia and those that don’t. The very first sentence of the abstract didn’t give me much hope for what followed. That sentence was: “Different guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend from the different pharmacological strategies adopted for intensifying glycemic control.” Did you catch the misprint?
This meta-analysis of 13 clinical trials was looking for differences in various health outcomes over the course of at least two years, comparing successful intensive management to standard care or placebo. Successful intensive management was defined as at least a 0.5% (6 mmol/mol) improvement in hemoglobin A1c (HgbA1c) level. “Intensification” of drug therapy is usually applied to a patient who is not at goal HgbA1c level. Undoubtedly, the benefits of intensification will be greater for those at HgbA1c of 10% than for those at 7.5%. BTW, few large clinical trials include patients over 75 years of age.
For my U.S. readers, note that other countries often specify HgbA1c values as mmol/mol instead of %. And blood sugars are not our usual mg/dl, but instead reported as mmol/l. HbA1c of 7% equals 53 mmol/mol, which would indicate and average blood sugar of 154 mg/dl or 8.6 mmol/l. As another example, HbA1c of 6.5% is 48 mmol/mol, reflecting average blood sugar of 140 mg/dl or 7.8 mmol/l. Are you thoroughly confused yet?
In the general population, lowest levels of mortality are seen at HgbA1c’s around 5 to 5.5% (31 to 36.6 mmol/mol). The average healthy non-diabetic adult hemoglobin A1c is 5% (31 mmol/mol) and translates into an average blood sugar of 100 mg/dl (5.56 mmol/l). This will vary a bit from lab to lab. Most healthy non-diabetics would be under 5.7% (38.8 mmol/mol). In December, 2009, the American Diabetes Association established a hemoglobin A1c criterion for the diagnosis of diabetes: 6.5% (47.5 mmol/mol) or higher. Diagnosis of prediabetes involves hemoglobin A1c in the range of 5.7 to 6.4% (38.8 to 46.5 mmol/mol).
Some expert panels recommend aiming for HgbA1c under 7% (53 mmol/mol), others recommend under 6.5% (48 mmol/mol). A major point of debate between the two guideline goals, is that the lower you set the goal, the greater the risk of drug-induced hypoglycemia, which can be lethal. In the early 1980s, the only drugs we had for diabetes were insulin, sulfonylureas, and metformin. Two of those three can can cause hypoglycemia. Now, a majority of our type 2 diabetes drugs don’t cause hypoglycemia.
The Italian researchers did this meta-analysis as part of their effort to produce diabetes drug treatment guidelines for the Italian population. On to the study at hand…
What Did the Researchers Find?
Improved glycemic (blood sugar) control by intensive attention reduced the major cardiovascular event rate by 10% and reduced renal adverse events by 25% but did not affect overall mortality or eye complications.
Intensified therapy with hypoglycemia-inducing drugs did not reduce overall mortality.
Drugs without potential for causing hypoglycemia were linked to lower risk of major cardiovascular events, kidney adverse events, and overall mortality, for HgbA1c under 7% (53 mmol/mol).
In conclusion, the results of this meta-analysis of RCTs show that in people with T2DM the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular complications (major adverse cardiac events and renal adverse events) and all-cause mortality, at least for HbA1c levels above 7%. The reduction of HbA1c below that threshold could have some favorable effects, but there is no available direct evidence in this respect. When the reduction of HbA1c is achieved with drugs inducing hypoglycemia, a progressive reduction of complications and an increase in the risk of severe hypoglycemia is observed. Therefore, the choice of the most adequate HbA1c target for each patient with T2DM should be made considering an appropriate risk/benefit ratio.
I think the researchers were particularly glad to find that intensification of drug therapy can reduce risk of heart attack, stroke, kidney complications, and death; all this without the risk of hypoglycemia that comes with drugs like insulin and sulfonylureas. The lack of a mortality benefit from hypoglycemia-inducing drugs may also be important. The benefits of intensive drug therapy (or lack thereof) depend somewhat on the particular complication you’re trying to avoid, and on baseline HgbA1c. Drug therapy is complicated! I expect these researchers would recommend a treatment HgbA1c goal of <7% rather than <6.5%.
Steve Parker, M.D.
PS: Reduce your need for diabetes drugs by losing excess weight, exercising, and eating low-carb.
Jack Thomas is an 82-year-old newspaperman who unexpectedly learned he would die soon. He wrote about it at The Boston Globe. RTWT. If you’re old, you may need a tissue handy, in case you get something in your eye. He’s a talented writer. A few out-of-order excerpts:
“After a week of injections, blood tests, X-rays, and a CAT scan, I have been diagnosed with cancer. It’s inoperable. Doctors say it will kill me within a time they measure not in years, but months.
“As the saying goes, fate has dealt me one from the bottom of the deck, and I am now condemned to confront the question that has plagued me for years: How does a person spend what he knows are his final months of life?
“Atop the list of things I’ll miss are the smiles and hugs every morning from my beautiful wife, Geraldine, the greatest blessing of my life. I hate the notion of an eternity without hearing laughter from my three children. And what about my 40 rose bushes? Who will nurture them? I cannot imagine an afterlife without the red of my America roses or the aroma of my yellow Julia Childs.
“We told each of the three children individually. John Patrick put his face in his hands, racked with sobs. After hanging up the telephone, Jennifer doubled over and wept until her dog, Rosie, approached to lick away the tears but not the melancholy. Faith explained over the telephone that, if I could see her, she was weeping and wondering how she could get along without her dad. Now, she is on the Internet every day, snorkeling for new research, new strategies, new medications. My wife cries every morning, then rolls up her sleeves and handles all doctor appointments and medication. Without her . . . I cannot imagine.
“Editing the final details of one’s life is like editing a story for the final time. It’s the last shot an editor has at making corrections, the last rewrite before the roll of the presses. It’s more painful than I anticipated to throw away files and paperwork that seemed critical to my survival just two weeks ago, and today, are all trash. Like the manual for the TV that broke down four years ago, and notebooks for stories that will never be written, and from former girlfriends, letters whose value will plummet the day I die. Filling wastebasket after wastebasket is a regrettable reminder that I have squandered much of my life on trivia.
“Unlike Roman Catholics, Jews, and atheists, we Episcopalians are very good at fence-sitting. We embrace all viewpoints, and as a result, we are as confused as the Unitarians.
“Does the intensity of a fatal illness clarify anything? Every day, I look at my wife’s beautiful face more admiringly, and in the garden, I do stare at the long row of blue hydrangeas with more appreciation than before. And the hundreds and hundreds of roses that bloomed this year were a greater joy than usual, not merely in their massive sprays of color, but also in their deep green foliage, the soft petals, the deep colors and the aromas that remind me of boyhood. As for the crises in Cuba and Haiti, however, and voting rights and the inexplicable stubbornness of Republicans who refuse to submit to an inoculation that might save their lives — on all those matters, no insights, no thunderbolts of discovery. I remain as ignorant as ever.
“I’ll miss my homes in Cambridge and Falmouth. I’ll never again see the sun rise over the marsh off Vineyard Sound, never again see that little, yellow goldfinch that perched atop a hemlock outside my window from time to time so that both of us could watch the tide rise to cover the wetland.
“As death draws near, I feel the same uncomfortable transition I experienced when I was a teenager at Brantwood Camp in Peterborough, New Hampshire, packing up to go home after a grand summer. I’m not sure what awaits me when I get home, but this has certainly been an exciting experience. I had a loving family. I had a great job at the newspaper. I met fascinating people, and I saw myriad worldwide wonders. It’s been full of fun and laughter, too, a really good time.
Compared to no coffee-drinking, drinking four cups a day reduced overall death rate by 20%, reduced cardiovascular deaths by 40%, and reduced death rate form coronary artery disease by 30%. The study at hand was a meta-analysis involving over 80,000 folks with type 2 diabetes living in multiple studies and followed clinically for 5-20 years. “Cardiovascular deaths” are usually heart attacks, strokes, cardiac arrest, or heart failure.
I vaguely recall a study several decades ago linking coffee to pancreas cancer, one of the deadliest cancers. The research was subsequently discredited.
From Nutrition, Metabolism & Cardiovascular Diseases:
To evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.
PubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.
Drinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.
First, remember that blood pressure is reported as two numbers: systolic and diastolic. E.g., 135/92. The first number is the systolic number. A systolic pressure goal of under 120 mmHg may be better than the traditional goal of under 140, at least if you’re “at increased risk for cardiovascular disease.” The study at hand excluded folks with diabetes or prior stroke.
We randomly assigned 9,361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.
At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.
From the March 6, 2021, European Journal of Nutrition:
Evolutionary discordance may contribute to the high burden of chronic disease-related mortality in modern industrialized nations. We aimed to investigate the associations of a 7-component, equal-weight, evolutionary-concordance lifestyle (ECL) score with all-cause and cause-specific mortality.
Baseline data were collected in 2003-2007 from 17,465 United States participants in the prospective Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The ECL score’s components were: a previously reported evolutionary-concordance diet score, alcohol intake, physical activity, sedentary behavior, waist circumference, smoking history, and social network size. Diet was assessed using a Block 98 food frequency questionnaire and anthropometrics by trained personnel; other information was self-reported. Higher scores indicated higher evolutionary concordance. We used multivariable Cox proportional hazards regression models to estimate ECL score-mortality associations.
Over a median follow-up of 10.3 years, 3771 deaths occurred (1177 from cardiovascular disease [CVD], 1002 from cancer). The multivariable-adjusted hazard ratios (HR) (95% confidence intervals [CI]) for those in the highest relative to the lowest ECL score quintiles for all-cause, all-CVD, and all-cancer mortality were, respectively, 0.45 (0.40, 0.50), 0.47 (0.39, 0.58), and 0.42 (0.34, 0.52) (all P trend < 0.01). Removing smoking and diet from the ECL score attenuated the estimated ECL score-all-cause mortality association the most, yielding fifth quintile HRs (95% CIs) of 0.56 (0.50, 0.62) and 0.50 (0.46, 0.55), respectively.
Our findings suggest that a more evolutionary-concordant lifestyle may be inversely associated with all-cause, all-CVD, and all-cancer mortality. Smoking and diet appeared to have the greatest impact on the ECL-mortality associations.