{"id":629,"date":"2017-10-30T21:31:58","date_gmt":"2017-10-30T21:31:58","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=629"},"modified":"2017-10-31T00:43:57","modified_gmt":"2017-10-31T00:43:57","slug":"digging-deeper-in-response-to-reader-comments","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2017\/10\/30\/digging-deeper-in-response-to-reader-comments\/","title":{"rendered":"Digging Deeper in Response to Reader Comments"},"content":{"rendered":"

Thank you, readers, for a lively dialog that has developed at the bottom of this page over the last few weeks, touching on some subjects that I have written about and many that I haven\u2019t written about. \u00a0I will take this space to respond to some of what you\u2019ve written about. \u00a0Some of my favorite topics include exercise, epigenetics, NSAIDs, and the gut microbiome.\u00a0 Reports of whole-body rejuvenation with the four “Yakanaka factors” is especially promising. I\u2019m grateful to Dr Paul Rivas <\/a>for many of the ideas that I\u2019ve expanded on here.<\/span><\/i><\/p>\n

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Aspirin, Ibuprofen, Naproxen<\/b><\/p>\n

Background:<\/b> COX2 inhibitors were found to reduce pain and inflammation of arthritis, but most COX2 inhibitors also inhibit COX1. \u00a0It is the COX1 inhibition that led to stomach damage and ulcer risk. \u00a0So in the 1990s, the pharma industry set out to find drugs that would inhibit COX2 without inhibiting COX1. \u00a0Only later, it came to light that these drugs elevated risk of heart disease, though they lowered the risk of cancer. \u00a0(Merck <\/span>knew of the dangers of Vioxx<\/span><\/a> before anyone else, but kept the stats under their hat as long as they could.) The worst offender, Vioxx=rofecoxib was taken off the market. \u00a0Only after CV statistics made the problem clear, researchers were led to ask, Why? \u00a0The problem is endemic. \u00a0Turns out that COX2 <\/span>plays a role in maintenance of arterial health<\/span><\/a>, and generally the NSAIDs increase heart risk <\/span>to the extent that they inhibit COX2<\/span><\/a>.\u00a0 It turned out that Vioxx was dangerous because it did too well exactly what it was designed to do.<\/span><\/p>\n

This story hangs together until we consider aspirin. \u00a0Aspirin inhibits both COX1 and COX2, and yet the preponderance of studies appear to show aspirin is associated with reduced CV risk [<\/span>ref<\/span><\/a>, <\/span>ref<\/span><\/a>]. \u00a0This suggests there is a piece of the metabolic puzzle that is still missing. \u00a0Aspirin has <\/span>many mechanisms of action<\/span><\/a>, some of them unique to aspirin.<\/span><\/p>\n

 <\/p>\n

My advice<\/span><\/a>, longstanding, has been to take \u00bc to 1 whole aspirin or ibuprofen a day (not both; not to be mixed in the same week) after about age 50 for lowered inflammation and protection from heart disease and cancer. \u00a0Evidence for protective effect of aspirin has weakened a bit in recent years, but is still holding up [<\/span>2016<\/span><\/a>]. \u00a0For patients who have already had a heart attack, aspirin remains standard protocol, and evidence for this population is strongest.<\/span><\/p>\n

Readers pointed to this study [<\/span>2017<\/span><\/a>], which reports elevated risk of heart attack for people taking ibuprofen or naproxen. \u00a0The dosages they are looking at are several times higher than the daily dosage used for prevention alone.<\/span><\/p>\n

All the NSAIDs have powerful effects in reducing cancer risk. \u00a0Glossing over the different numbers for different kinds of cancer with different NSAIDs in different studies, it\u2019s a good rule of thumb that taking low-dose NSAIDs daily cuts cancer risk in half. [<\/span>ref<\/span><\/a>]<\/span><\/p>\n

Effects on cardiovascular risk are more complicated. \u00a0I have been unable to find direct comparisons of aspirin vs ibuprofen and others, but there is \u201ccircumstantial\u201d evidence in the literature that aspirin slightly decreases CV risk, while all the others slightly increase risk. \u00a0Different studies rank the NSAIDs differently. \u00a0There is suspicion of the \u201ccoxib\u201d drugs which many people find work well for arthritis, but the latest studies show this seems to be unfounded. \u00a0This study [<\/span>2016<\/span><\/a>] finds Celecoxib (Celebrex) is safer than either ibuprofen or naproxen (Alleve), and results in both lower CV risk and lower all-cause mortality.<\/span><\/p>\n

There may be other reasons to prefer one or another NSAID. \u00a0There are benefits for joint pain and stiffness; there are risks for gastric pain and ulcers. \u00a0It\u2019s an individual choice, and I encourage you to experiment on yourself. \u00a0You can alternate different NSAIDs, but it\u2019s best to do so week-by-week or month-by-month, rather than daily. \u00a0Don\u2019t take aspirin and other NSAIDs in the same week.<\/span><\/p>\n

 <\/p>\n

Does too much exercise cause areterial calcification?<\/b><\/p>\n

Readers pointed to this study [<\/span>2017<\/span><\/a>] from Mayo Clinic, in which young adults were followed for 25 years, and those who exercised most hours per week had elevated calcification of their arteries. \u00a0Calcification, in turn, is correlated with higher risk of heart disease.<\/span><\/p>\n

There are several reasons I\u2019m not turning on a dime to change my advice about exercise (which has always been, \u201cthe more, the better\u201d).<\/span><\/p>\n

    \n
  1. It\u2019s a new finding. \u00a0The study is still in preprint form, and cites no precedent.<\/span><\/li>\n
  2. It\u2019s based on just 268 subjects.<\/span><\/li>\n
  3. The people in the high-exercise\/high-calcification group did the equivalent of 7 or more hours of jogging each week. \u00a0But the study didn\u2019t separate recreational from occupational exercise. \u00a0Social class is a really big factor, and it may be that all we\u2019re seeing is that working class people have more CV symptoms than the upper middle class.<\/span><\/li>\n
  4. The fact that exercise is correlated with calcification and calcification is correlated with increased heart risk <\/span>does not<\/i><\/b> necessarily imply that exercise is correlated with heart risk. \u00a0This is such a common mistake.\u00a0 (A correlated with B) and (B correlated with C) does not let you conclude that A is correlated with C. \u00a0<\/span>In fact, the paper explicitly cites precedent that people who exercise most have lowest CV risk <\/i><\/b>[<\/span>ref<\/span><\/a>, <\/span>ref<\/span><\/a>]<\/span>.<\/b><\/li>\n
  5. So many benefits of exercise for so many aspects of health have been documented over the years that exercise is one of the solidest pillars of any health and longevity program.<\/span><\/li>\n<\/ol>\n

    The <\/span>Copenhagen City Heart Study<\/span><\/a> gave me more pause. \u00a0They found that joggers who ran at a moderate pace 2-3 hours per week had longest lifespans. \u00a0The benefit was about 6 years of life (a big number compared to every other life extension strategy that\u2019s been studied, with the exception of caloric restriction). \u00a0But runners who worked longer and harder than this lost the benefit and, in fact, died early. \u00a0There is support for this thesis in other articles as well [<\/span>ref<\/span><\/a>, <\/span>ref<\/span><\/a>]. \u00a0But there are also studies claiming that there is only a law of diminishing returns, and no amount or intensity of exercise that is actually bad for longevity [<\/span>ref<\/span><\/a>, <\/span>ref<\/span><\/a>]. \u00a0<\/span><\/p>\n

    I have not figured out the reason that different studies come to different conclusions, but here is what they agree on: \u00a0<\/span><\/p>\n