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Found 21 results

  1. Dean Pomerleau

    So Why Don't We Brew Our Olive Oil?

    All, Like Michael, I've got a huge backlog of posts I want to get to, and unlike Michael, I'm actually planning to get to them all. So I'm going to try to keep this one short. We'll see how that works out... OK - I admit brewing olive oil is a strange idea, and really a misnomer. The title is an allusion to a similar thread about chocolate/cacao - So Why Don't We Brew Our Chocolate? Brewing chocolate, instead of eating it, is a practice I've engaged in since that thread began in November, in order to get the health-promoting phytonutrients in cacao without the calories, refined sugar, saturated fat or heavy metals (e.g. cadmium) that chocolate products generally contain. Now, in researching this recent post for the cold exposure thread about the ability of extra virgin olive oil (EVOO) and olive leaf extract (OLE) to promote beneficial thermogenesis and the browning of white fat, I realized the same argument about brewing vs. eating can and perhaps should be made for olive polyphenols that I made for cacao polyphenols in the brewing chocolate thread. As we all know by now, EVOO may be one of the keys to the health benefits of a Mediterranean diet, although it's merits relative to nuts & seeds is a perennial topic of debate on these forums. I personally come down on the side of nuts & seeds. But one thing I believe everyone can agree on, is that, while the MUFA in EVOO is relatively harmless compared to other forms of fat, the real reason EVOO is considered healthy are all the polyphenols it contains. In fact, I'd go so far as to say Michael (and other extremely health conscious individuals) wouldn't touch refined olive oil (without the polyphenols but with the MUFA) with a 10-foot pole - the polyphenols are that critical to EVOO's benefits. So if it's all about the polyphenols, why can't we get them without all the fat and calories of EVOO? It seems to me that we can, and in a form not much different in degree of refinement than EVOO. How you ask? Sure, we could eat olives. In fact store-bought olives have about 400mg/kg total polyphenols [1], higher than the minimum level Michael insists on for his high-quality, high-polyphenol EVOO (350 mg/kg). So if you aren't worried about the salt, store-bought olives might be a better option for getting your olive polyphenols, since kg-for-kg, calorie-for-calorie, and certainly dollar-for-dollar, they are a much better source of polyphenols. But before you go out and raid the antipasto bar at your local supermarket, one other potential shortcoming of olives is the fact that olives appears to maintain the same (or better) total polyphenol content as EVOO, the curing process used to debitter olives shifts which polyphenols are present. In particular, curing reduces the (bitter tasting) polyphenol oleuropein which is high in fresh olives (and high-quality EVOO), and replace it with two other derivative polyphenols, hydroxytyrosol and tyrosol. I'm not totally sure if this polyphenol shift is a step down or a step up, but it certain is a change, and most of the evidence for benefits of EVOO seem to point to the oleuropein (see below). So eating olives isn't the equivalent of eating EVOO, in terms of polyphenols (or salt or fat, obviously). So is there a better alternative to EVOO and olives that can provide the same (or higher) total polyphenol content, and in the same ratio as demonstrably healthy high-quality EVOO? Unfortunately, raw, uncured olives don't seem to be available, at least not on the biggest store in the world (Amazon). Anyone ever eaten them fresh off the tree? I bet they taste really bad. But there may be a better alternative, in the form of olive leaves and olive leaf tea. Now would be a good time for anyone who hasn't read it to check out my recent post to the cold exposure thread about how olive polyphenols turn white fat cells to brown/beige, increasing thermogenesis, insulin sensitivity, SIRT1 and AMPK as additional nice side effects. In short, olive polyphenols cured what ailed these white fat cells. But what really caught my attention about that study (PMID 27303302), was the method they used to obtain the olive polyphenols. They took fresh picked olive leaves, dried them, soaked them in hot (80 °C) water for 24 hours, strained out the leaf solids, and then concentrated the resulting liquid by removing much of the water. to create Olive Leaf Extract (OLE). In short, they made a tea from olive leaves, which they and others call Olive Leaf Extract (OLE). How do the polyphenols concentration and ratio in OLE compare with high-quality EVOO? The details are in that post, so I won't repeat them here. But to summarize, unlike cured olives, but like EVOO, Oleuropein was the most abundant polyphenol in OLE, along with (apparently) all the other major polyphenols in EVOO. So how much polyphenols are there in OLE? The authors of that study found their olive leaf tea concentrate (OLE) contained 40mg of total phenolics per gram. That equates to 40,000mg/kg (40g/kg) of polyphenols, or about two orders of magnitude higher concentration of polyphenols in the OLE than in Michael's top-notch olive oils or in cured olives themselves. So OLE, at least the way these researchers prepared it, is pretty potent stuff - a little goes a long way! So what about benefits of OLE vs. EVOO? As I discussed in detail in the cold exposure post above, OLE appears to boost BAT activity both in vitro and in vivo, just like EVOO. It looks like the polyphenol oleuropein, rich in EVOO and especially rich in OLE, is where the cardioprotective and neuroprotective effects come from [3]. LEF has a good review article with references to all the benefits of OLE and oleuropein, including improvements in blood pressure, arterial health, brain health, diabetes risk, cancer risk, and arthritis. But you might be saying - I like to eat whole foods, and olive leaf extract doesn't seem to qualify. Obviously EVOO, even of highest quality, isn't a whole food either. In fact, EVOO and OLE are quite similar, except the former has a lot more fat. And clearly green tea, coffee, or cocoa powder aren't whole foods either, but people around here generally consider them quite healthy. You may be saying by now "OK Dean, you've piqued my interest. How can I get my hands on some of this OLE stuff?" Not surprisingly, LEF and other nutraceutical vendors sells it in capsule form. For $0.36, one LEF OLE capsule contains 80mg of oleuropein among other polyphenols, the equivalent amount in about 200ml of the very highest quality EVOO, according to this table. That amount of high-quality EVOO will cost you about $8, and 1800 calories. Seems like a pretty good bargain to me... For those of you (like me) who'd rather not get your nutrition from pills if you can help it, you can buy dried olive leaves inexpensively in whole or powder form, for making tea. One benefit of being so busy posting about other topics, is that this post about OLE was delayed for a few days since I made the post over on the cold exposure thread which brought OLE to my attention. That gave me time to put my money where my mouth is, by ordering, receiving and testing out the Frontier organic whole olive leaf powder linked to above. All I can say is that if oleuropein is what makes EVOO and OLE bitter (and healthy), this stuff has a lot of oleuropein! Eating even a tiny pinch straight is not pleasant - to put it mildly. Fortunately as we saw above, it doesn't take much. I'm now adding just a pinch per day of olive leaf powder to my coffee/tea/cacao concoction, which has enough flavors in it that I don't even notice the OLE's unpleasant taste. Plus by cold brewing it overnight, warm brewing it briefly in the morning, and filtering the heck out of it, I'm eliminating any nastiness left in the solids. The powder I purchased are supposed to be from organic olive leaves, but who knows... Just like with cadmium from the soil in cacao, lead in tea leaves etc. In summary, if you are interested in the benefits of the highest quality olive oil, without the financial or calorie burden, you might seriously consider olive leaf extract or olive leaf tea as alternatives. I'm curious, has anyone else tried olive leaf products, and if so (or even if not), what do you think? --Dean --------- [1] J Agric Food Chem. 2004 Feb 11;52(3):479-84. Effect of cultivar and processing method on the contents of polyphenols in table olives. Romero C(1), Brenes M, Yousfi K, García P, García A, Garrido A. Author information: (1)Food Biotechnology Department, Instituto de la Grasa (CSIC), Avenida Padre García Tejero 4, Seville, Spain. Full text: http://sci-hub.cc/10.1021/jf030525l Polyphenols were determined by HPLC in the juice and oil of packed table olives. The phenolic compositions of the two phases were very different, hydroxytyrosol and tyrosol being the main polyphenols in olive juice and tyrosol acetate, hydroxtyrosol acetate, hydroxytyrosol, tyrosol, and lignans (1-acetoxypinoresinol and pinoresinol) in oil. The type of processing had a marked influence on the concentration of polyphenols in olive juice and little on the content in oil. The analyses carried out on 48 samples showed that turning color olives in brine had the highest concentration in polyphenols ( approximately 1200 mg/kg), whereas oxidized olives had the lowest ( approximately 200 mg/kg). Among olive cultivars, Manzanilla had a higher concentration than Hojiblanca and Gordal. The type of olive presentation also influenced the concentration of polyphenols in olives, decreasing in the order plain > pitted > stuffed. The results obtained in this work indicate that table olives can be considered a good source of phenolic antioxidants, although their concentration depends on olive cultivar and processing method. PMID: 14759136 ----------- [2] J Agric Food Chem. 2012 Jul 25;60(29):7081-95. doi: 10.1021/jf3017699. Epub 2012 Jul 11. Factors influencing phenolic compounds in table olives (Olea europaea). Charoenprasert S(1), Mitchell A. Author information: (1)Department of Food Science and Technology, University of California, One Shields Avenue, Davis, California 95616, United States. The Mediterranean diet appears to be associated with a reduced risk of several chronic diseases including cancer and cardiovascular and Alzheimer's diseases. Olive products (mainly olive oil and table olives) are important components of the Mediterranean diet. Olives contain a range of phenolic compounds; these natural antioxidants may contribute to the prevention of these chronic conditions. Consequently, the consumption of table olives and olive oil continues to increase worldwide by health-conscious consumers. There are numerous factors that can affect the phenolics in table olives including the cultivar, degree of ripening, and, importantly, the methods used for curing and processing table olives. The predominant phenolic compound found in fresh olive is the bitter secoiridoid oleuropein. Table olive processing decreases levels of oleuropein with concomitant increases in the hydrolysis products hydroxytyrosol and tyrosol. Many of the health benefits reported for olives are thought to be associated with the levels of hydroxytyrosol. Herein the pre- and post-harvest factors influencing the phenolics in olives, debittering methods, and health benefits of phenolics in table olives are reviewed. PMID: 22720792 --------- [3] Saudi Pharm J. 2010 Jul;18(3):111-21. doi: 10.1016/j.jsps.2010.05.005. Epub 2010 May 31. Cardioprotective and neuroprotective roles of oleuropein in olive. Omar SH(1). Author information: (1)College of Pharmacy, Qassim University, P.O. Box 31922, Buraidah-51418, Saudi Arabia. Traditional diets of people living in the Mediterranean basin are, among other components, very rich in extra-virgin olive oil, the most typical source of visible fat. Olive is a priceless source of monounsaturated and di-unsaturated fatty acids, polyphenolic antioxidants and vitamins. Oleuropein is the main glycoside in olives and is responsible for the bitter taste of immature and unprocessed olives. Chemically, oleuropein is the ester of elenolic acid and 3,4-dihydroxyphenyl ethanol, which possesses beneficial effects on human health, such as antioxidant, antiatherogenic, anti-cancer, anti-inflammatory and antimicrobial properties. The phenolic fraction extracted from the leaves of the olive tree, which contains significant amounts of oleuropein, prevents lipoprotein oxidation. In addition, oleuropein has shown cardioprotective effect against acute adriamycin cardiotoxicity and an anti-ischemic and hypolipidemic activities. Recently, oleuropein has shown neuroprotection by forming a non-covalent complex with the Aβ peptide, which is a key hallmark of several degenerative diseases like Alzheimer and Parkinson. Thus, a large mass of research has been accumulating in the area of olive oil, in the attempt to provide evidence for the health benefits of olive oil consumption and to scientifically support the widespread adoption of traditional Mediterranean diet as a model of healthy eating. These results provide a molecular basis for some of the benefits potentially coming from oleuropein consumption and pave the way to further studies on the possible pharmacological use of oleuropein to prevent or to slow down the cardiovascular and neurodegenerative diseases. PMCID: PMC3730992 PMID: 23964170
  2. Todd Allen

    What's Wrong with Eggs Now?!

    [Admin Note: Over on the LDL particle size thread, Todd asked the question of why eggs are bad. Seems like a question that deserves its own thread, given the recent supposed exoneration of dietary cholesterol. So here it is.] The important difference between consumption of dietary cholesterol, which has a negligible influence on heart disease risk, and cholesterol produced endogenously in the body (which can be a marker of risk, depending on a complete profile).... So why exactly is it that eggs are so damn bad? http://www.whfoods.com/genpage.php?tname=foodspice&dbid=92
  3. [Admin Note: I made this new thread as a collector for posts about the recently discovered and previously discussed apparent link between diet, micronutrients choline and carnitine, TMAO production by gut microbes that feed on these micronutrients, and elevated risk of cardiovascular disease. Four posts down is the new post (by me) on the topic. The first four posts come from a different thread. --Dean] In his post about supplements for vegetarians, Michael Rae said: For now, prudence seems to require that vegetarians err on the side of a generous and definitely supplemented intake of choline, ensuring that dietary (to the extent that it can be known) plus supplemental choline is meaningfully higher than the AI of 550 mg for men and 425 mg/day for women. Functional status is still tricky, but one obvious set of markers is the same panel used to establish signs of deficiency in Zeisel’s depletion-repletion study:iv a fivefold or more increase above normal of the muscle-damage enzyme creatine phosphokinase (CPK), or a one-and-a-half or more times normal reading of the liver enzymes aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), or lactate dehydrogenase (LD). Fatty liver, unfortunately, requires a harder-to-access MRI of fat deposits in the organ, to which your doctor is unlikely to consent. The below papers may be a reason dietary choline can be bad for us. NATURE | RESEARCH HIGHLIGHTS CARDIOVASCULAR BIOLOGY Gut microbes raise heart-attack risk Nature 531, 278 (17 March 2016) doi:10.1038/531278b Published online 16 March 2016 http://sci-hub.io/10.1038/531278b Subject terms: Microbiology Cardiovascular biology Gut microbes produce a chemical that enhances clotting in the arteries, increasing the risk of heart attack and stroke. Stanley Hazen of the Cleveland Clinic in Ohio and his colleagues treated human platelets, which form blood clots, with a compound called TMAO. This is made in the body from a waste product of gut microbes, and has been linked to heart disease. The team found that TMAO made the platelets form artery-blocking clots faster. The researchers increased blood TMAO levels in mice by feeding them a diet that was rich in choline, a TMAO precursor, and found that the animals formed clots faster than did those with lower TMAO levels. This effect was not seen in animals that lacked gut microbes or that were treated with antibiotics. When intestinal microbes from mice that produced high levels of TMAO were transplanted into mice with no gut microbes, the recipients' clotting risk increased. The results reveal a link between diet, gut microbes and heart-disease risk, the authors say. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, Li L, Fu X, Wu Y, Mehrabian M, Sartor RB, McIntyre TM, Silverstein RL, Tang WH, DiDonato JA, Brown JM, Lusis AJ, Hazen SL. Cell. 2016 Mar 9. pii: S0092-8674(16)30113-1. doi: 10.1016/j.cell.2016.02.011. [Epub ahead of print] PMID: 26972052 http://sci-hub.io/10.1016/j.cell.2016.02.011 Abstract Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n > 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.
  4. Does anyone else eat natto, the fermented soybean product which is quite popular in Japan? It is the richest food source of vitamin K2 (menaquinone-7 or MK-7) with 1 mg (1000 mcg) of K2 per 100g natto. That is about 20x higher than the next highest source, certain cheeses like Gouda. Unlike vitamin K1 which is found primarily in leafy greens, there is virtually no vitamin K2 in regular fruits and vegetables. Why should we care about vitamin K2 you ask? First and foremost because it has been shown to be protective against osteoporosis [1-2], a concern for CR practitioners. From [2], a study of 244 postmenopausal women supplemented with 180mcg/day of Vitamin K2 (MK-7) for three years: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. CONCLUSIONS: MK-7 supplements may help postmenopausal women to prevent bone loss. Another significant benefit of Vitamin K2 is for cardiovascular health. Vitamin K2 seems to prevent artery calcification (aka hardening of the arteries) [3-5], which happens when calcium circulating in the blood is turned into a crust in the arteries. In study [5] the same group of researchers from [2] measured arterial calcification in the same 244 postmenopausal women on 180mcg/day of K2 for three years, and found multiple markers of arterial stiffness improved with K2 supplementation, concluding: Long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. But those were studies of direct supplementation of vitamin K2 (MK-7), rather than getting it from food. Does eating natto actually raise serum MK-7 levels? Thankfully the answer is yes, according to [6]: erum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. So where to get natto? I buy my natto in frozen form at my local asian market, for about $2.50 for four styrofoam containers each of which contains about 50g of natto. Here is what the package of four look like: I eat half of a container's worth of natto per day (cost ~ $0.30/day). That 25g of natto per day provides about 250mcg of Vitamin K2 (MK-7), which is about 30% more than the dose shown to improve bone health [2] and reduce arterial stiffness [5] in postmenopausal women. What's natto like you ask? There is no getting around the fact that it looks pretty gross, and has a very slimy texture. As a result, many people can't stomach it, but I actually enjoy the taste, especially when mixed into the serving of other legumes and starches I eat. Below is a photo of natto in the styrofoam container. Pretty appetizing, huh?! The chopsticks in the photo are helpful for scale: For those of you who would be too grossed out by natto to eat it, there are supplements available. In fact I take one of these* to increase my K2 beyond what I get from natto - adding an extra 100mcg MK-7 per day for $0.09. But I'm always in favor of getting nutrients from food sources when practical. This is one of the rare cases where the natural food source is price competitive with supplement sources. So for me natto is a good choice. Does anyone else eat natto? If not, you might consider giving it a try! [Note: This post does not address Natto's brain health benefits. For discussion of that, see this post further down this thread.] --Dean *Note - I've updated my supplement regime to this vegan NOW Foods brand K2 supplement, to make sure I'm getting K2 in MK-7 form, rather than (mostly) MK-4 per my previous supplement. --------- [1] J Bone Miner Metab. 2014 Mar;32(2):142-50. doi: 10.1007/s00774-013-0472-7. Epub 2013 May 24. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. Koitaya N(1), Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y. Author information: (1)Department of Food Function and Labeling, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjyuku-ku, Tokyo, Japan. Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. The participants (aged 50-65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects. PMID: 23702931 ------------ [2] Osteoporos Int. 2013 Sep;24(9):2499-507. doi: 10.1007/s00198-013-2325-6. Epub 2013 Mar 23. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Knapen MH(1), Drummen NE, Smit E, Vermeer C, Theuwissen E. Author information: (1)VitaK, Maastricht University, Oxfordlaan 70, 6229 EV, Maastricht, The Netherlands. We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.INTRODUCTION: Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health. METHODS: Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment. RESULTS: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. CONCLUSIONS: MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation. PMID: 23525894 ----------- [3] Acta Physiol Hung. 2010 Sep;97(3):256-66. doi: 10.1556/APhysiol.97.2010.3.2. Vitamin K and vascular calcifications. Fodor D(1), Albu A, Poantă L, Porojan M. Author information: (1)University of Medicine and Pharmacy, 2nd Internal Medicine, Clinic Iuliu Hatieganu, Cluj-Napoca, Romania. dfodor@umfcluj.ro The role of vitamin K in the synthesis of some coagulation factors is well known. The implication of vitamin K in vascular health was demonstrated in many surveys and studies conducted over the past years on the vitamin K-dependent proteins non-involved in coagulation processes. The vitamin K-dependent matrix Gla protein is a potent inhibitor of the arterial calcification, and may become a non-invasive biochemical marker for vascular calcification. Vitamin K(2) is considered to be more important for vascular system, if compared to vitamin K(1). This paper is reviewing the data from recent literature on the involvement of vitamin K and vitamin K-dependent proteins in cardiovascular health. PMID: 20843764 ---------------- [4] Nutrients. 2015 Aug 18;7(8):6991-7011. doi: 10.3390/nu7085318. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification. Scheiber D(1), Veulemans V(2), Horn P(3), Chatrou ML(4), Potthoff SA(5), Kelm M(6,)(7), Schurgers LJ(8), Westenfeld R(9). Author information: (1)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. daniel.scheiber@med.uni-duesseldorf.de. (2)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. verena.veulemanns@med.uni-duesseldorf.de. (3)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. patrick.horn@med.uni-duesseldorf.de. (4)Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands. m.chatrou@maastrichtuniversity.nl. (5)Department of Nephrology, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany. sebastian.potthoff@med.uni-duesseldorf.de. (6)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (7)Cardiovascular Research Institute Duesseldorf, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (8)Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands. l.schurgers@maastrichtuniversity.nl. (9)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. ralf.westenfeld@med.uni-duesseldorf.de. Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMCID: PMC4555157 PMID: 26295257 ------------- [5] Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C(1). Author information: (1)Cees Vermeer, PhD, VitaK, Maastricht University, Biopartner Center Maastricht, Oxfordlaan 70, 6229 EV Maastricht, The Netherlands, Tel: +31 43 388 5865, Fax: +31 43 388 5889, E-mail: c.vermeer@vitak.com. Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. PMID: 25694037 ---------- [6] J Bone Miner Metab. 2000;18(4):216-22. Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals. Tsukamoto Y(1), Ichise H, Kakuda H, Yamaguchi M. Author information: (1)Central Research Institute, Mitsukan Group Co., Ltd., Aichi, Japan. Changes in circulating vitamin K2 (menaquinone-7, MK-7) and gamma-carboxylated osteocalcin concentrations in normal individuals with the intake of fermented soybeans (natto) were investigated. Eight male volunteers were given sequentially fermented soybeans (natto) containing three different contents of MK-7 at an interval of 7 days as follows: regular natto including 775 micrograms/100 g (MK-7 x 1) or reinforced natto containing 1298 micrograms/100 g (MK-7 x 1.5) or 1765 micrograms/100 g (MK-7 x 2). Subsequently, it was found that serum MK-7 and gamma-carboxylated osteocalcin concentrations were significantly elevated following the start of dietary intake of MK-7 (1298 or 1765 micrograms/100 g). Serum undercarboxylated osteocalcin concentrations were significantly decreased by dietary MK-7 (1765 micrograms/100 g) supplementation. Moreover, the changes in serum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. The present study suggests that intake of fermented soybean (natto) increases serum levels of MK-7 and gamma-carboxylated osteocalcin in normal individuals. PMID: 10874601
  5. All, I'm not sure if many people around here still do dairy, especially high fat dairy. But if you do, you might want to think again, and not just for the sake of the animals, but for the sake of your heart. This new study [1] analyzed the data from over 200K people in the Health Care Professionals and Nurses Health Studies followed for 20-30 years. The good news? Dairy fat intake was associated with a slightly lower cardiovascular disease risk than other forms of animal fat. The bad news? Replacing 5% of energy from PUFA for 5% more dairy fat resulted in a 24% increase in your risk of cardiovascular disease. Replacing dairy with whole grains was even better (28% lower risk of CVD). Here is a graph showing the estimated impact of substituting various other foods in place of dairy fat on risk of cardiovascular disease overall (A), as well as broken down by coronary heart disease (B) vs. stroke (C ): The authors summarize as follows: To our knowledge, this is the first large-scale prospective study to examine dairy fat intake and its replacement with other types of fat in relation to CVD risk... These results support current recommendations to replace animal fats, including dairy fat, with vegetable sources of fats and polyunsaturated fat (both n–6 and n–3) in the prevention of CVD. Sorry to be the bearer of bad news, cheese lovers. Whom I kidding, no I'm not... --Dean ------------ [1] Am J Clin Nutr. 2016 Aug 24. pii: ajcn134460. [Epub ahead of print] Dairy fat and risk of cardiovascular disease in 3 cohorts of US adults. Chen M(1), Li Y(2), Sun Q(3), Pan A(4), Manson JE(5), Rexrode KM(5), Willett WC(6), Rimm EB(6), Hu FB(7). Full text: http://sci-hub.cc/10.3945/ajcn.116.134460 BACKGROUND: Few prospective studies have examined dairy fat in relation to cardiovascular disease (CVD). OBJECTIVE: We aimed to evaluate the association between dairy fat and incident CVD in US adults. DESIGN: We followed 43,652 men in the Health Professionals Follow-Up Study (1986-2010), 87,907 women in the Nurses' Health Study (1980-2012), and 90,675 women in the Nurses' Health Study II (1991-2011). Dairy fat and other fat intakes were assessed every 4 y with the use of validated food-frequency questionnaires. RESULTS: During 5,158,337 person-years of follow-up, we documented 14,815 incident CVD cases including 8974 coronary heart disease cases (nonfatal myocardial infarction or fatal coronary disease) and 5841 stroke cases. In multivariate analyses, compared with an equivalent amount of energy from carbohydrates (excluding fruit and vegetables), dairy fat intake was not significantly related to risk of total CVD (for a 5% increase in energy from dairy fat, the RR was 1.02; 95% CI: 0.98, 1.05), coronary heart disease (RR: 1.03; 95% CI: 0.98, 1.09), or stroke (RR: 0.99; 95% CI: 0.93, 1.05) (P > 0.05 for all). In models in which we estimated the effects of exchanging different fat sources, the replacement of 5% of energy intake from dairy fat with equivalent energy intake from polyunsaturated fatty acid (PUFA) or vegetable fat was associated with 24% (RR: 0.76; 95% CI: 0.71, 0.81) and 10% (RR: 0.90; 95% CI: 0.87, 0.93) lower risk of CVD, respectively, whereas the 5% energy intake substitution of other animal fat with dairy fat was associated with 6% increased CVD risk (RR: 1.06; 95% CI: 1.02, 1.09). CONCLUSIONS: The replacement of animal fats, including dairy fat, with vegetable sources of fats and PUFAs may reduce risk of CVD. Whether the food matrix may modify the effect of dairy fat on health outcomes warrants further investigation. © 2016 American Society for Nutrition. DOI: 10.3945/ajcn.116.134460 PMID: 27557656
  6. All, As I've elaborated on elsewhere, I'm rather obsessive about dental hygiene. This is in part because I want to avoid cavities, but also out of a vague awareness of studies linking teeth & gum problems with heart attack risk, likely mediated by systemic inflammation induced by chronic oral infections. So I was happy to see my recall of the linkage between poor dental health and cardiovascular disease supported by this new study [2], as well as this review [1] of many previous studies, both of which were shared by Al Pater (thanks Al!). From the review [1]: [N]ew onset as well as prevalent periodontitis is associated with increased coronary heart disease risk,7 and there is a graded association between tooth loss and stroke, cardiovascular death, and all-cause mortality in patients with stable coronary artery disease.8 From the case-control study [2]: There was an increased risk for [heart attack] among those with [periodontal disease] (OR = 1.49; 95% CI 1.21-1.83), which remained significant (OR =1.28; 95% CI 1.03-1.60) after adjusting for variables that differed between patients and controls (smoking habits, diabetes, years of education and marital status). So we should all be taking good care of our teeth and gums if we want to avoid cardiovascular disease. --Dean ----------------- [1] Circulation. 2016 Jan 13. pii: CIRCULATIONAHA.115.020869. [Epub ahead of print] Increasing Evidence for an Association Between Periodontitis and Cardiovascular Disease. Stewart R, West M. http://circ.ahajournals.org.sci-hub.io/content/early/2016/01/13/CIRCULATIONAHA.115.020869.abstract Abstract Periodontitis is a chronic inflammatory disease caused by bacterial colonisation, which results in destruction of the tissues between the tooth surface and gingiva, loss of connective tissue attachment, erosion of alveolar bone and tooth loss.1 Periodontitis is common and increases with age. In a US survey about half of adults aged over 30 years have some periodontitis and almost 10% have severe disease.2 Evidence for an association between periodontitis and atherosclerotic vascular disease, including stroke, myocardial infarction, peripheral vascular disease, abdominal aortic aneurysm, coronary heart disease and cardiovascular death, comes from more than 50 prospective cohort and case control studies undertaken during the last 25 years.3-6 More recent analyses from large cohort studies suggest new onset as well as prevalent periodontitis is associated with increased coronary heart disease risk,7 and there is a graded association between tooth loss and stroke, cardiovascular death, and all-cause mortality in patients with stable coronary artery disease.8 If causal, these associations would be of great importance because of the potential that preventing or treating periodontal disease could reduce the risk of major adverse cardiovascular events. KEYWORDS: Editorial; cardiovascular disease risk factors; periodontitis; teeth PMID: 26762522 --------------- [2] Circulation. 2016 Jan 13. pii: CIRCULATIONAHA.115.020324. [Epub ahead of print] Periodontitis Increases the Risk of a First Myocardial Infarction: A Report From the PAROKRANK Study. Rydén L, Buhlin K, Ekstrand E, de Faire U, Gustafsson A, Holmer J, Kjellström B, Lindahl B, Norhammar A, Nygren Å, Näsman P, Rathnayake N, Svenungsson E, Klinge B. Abstract BACKGROUND: -The relationship between periodontitis (PD) and cardiovascular disease (CVD) is debated. PD is common in patients with CVD. It has been postulated that PD could be causally related to the risk for CVD, a hypothesis tested in PAROKRANK. METHODS AND RESULTS: -805 patients (age <75 years) with a first MI and 805 age (mean 62±8), gender (male 81%) and area matched controls without MI underwent standardized dental examination including panoramic x-ray. The periodontal status was defined as healthy (=/>80% remaining bone) or as mild-moderate (79-66%) or severe PD (<66%). Great efforts were made to collect information on possibly related confounders (~100 variables). Statistical comparisons included Student's pair-wise t-test and Mc Nemar's test in 2x2 contingency tables. Contingency tables exceeding 2x2 with ranked alternatives were tested by Wilcoxon signed rank test. Odds Ratios (95% CI) were calculated by conditional logistic regression. PD was more common (43%) in patients than in controls (33%; p<0.001). There was an increased risk for MI among those with PD (OR = 1.49; 95% CI 1.21-1.83), which remained significant (OR =1.28; 95% CI 1.03-1.60) after adjusting for variables that differed between patients and controls (smoking habits, diabetes, years of education and marital status). CONCLUSIONS: -In this large case-control study of PD, verified by radiographic bone loss and with a careful consideration of potential confounders, the risk of a first MI was significantly increased in patients with PD even after adjustment for confounding factors. These findings strengthen the possibility of an independent relationship between PD and MI. KEYWORDS: cardiovascular disease risk factors; myocardial infarction; panoramic dental radiography (OPG); periodontitis PMID: 26762521
  7. All, We had a pretty long thread not too long ago about Total Cholesterol and Heart Attack Risk but as far as I can tell we haven't talked much about the relative value of a standard lipid panel vs. some of the newer tests for various LDL particle sizes, densities etc. I bring it up for two reasons: One is personal. A family member in their early 50s is an APOE4 carrier (single allele) and not surprisingly, has borderline high cholesterol (210 mg/dL total, 120 LDL, 55 HDL). They are otherwise thin, active, healthy with good fasting blood glucose. So it seems they are one of those borderline cases for statins, and I'm wondering whether getting their LDL particle sizes tested might provide some additional useful diagnostic information for making that decision. I would lean against starting statins in their case (due to possible side effects see below), but I'm wondering if the discovery that they have many (or very few) small dense LDL particles might tip the scales one way or the other. The second reason I bring it up is because I just listened to a long (1:20:00) but very interesting interview by Dr. Rhonda Patrick with Dr. Ronald Krauss, who appears to be a pioneer in research into cholesterol and CVD, the effects of diet on CVD risk, statin side effects, particle size testing etc. I found it really educational to learn more about the mechanics of atherosclerosis, e.g. the details of how inflammation is involved and why we might have evolved to work that way. How small LDL particles have the part of their surface structure occluded just where the liver's LDL-receptor tries to attach to them, making the small particles harder to clear from the bloodstream, making them stick around in the bloodstream for longer to get oxidized / glycated and to infiltrate the arterial walls. Lots of good stuff I didn't know before. But a couple caveats. I'm not an expert on the details of how atherosclerosis works, or anything about particle sizes, so while I found it interesting, I can't vouch for the validity of Dr. Krauss's perspective or the information he shared. And I will note that Dr. Krauss co-authored with Dr. Patty Siri-Tarino and several others a pretty poor and misleading meta-analysis which appeared to call into question the link between saturated fat and heart disease. Their meta-analysis has been roundly criticized briefly by Michael in this thread and more thoroughly by PlantPositive here. He also mentioned he's been sponsored by the dairy industry, and has a patent and receives royalties on a new cutting edge LDL particle measurement test called Cardio IQ® Lipoprotein Fractionation, Ion Mobility which is now available from Quest. So all that is to meant to suggest that one should take what Dr. Krauss says in this interview with a pretty grain of salt. I'd be curious to hear what anyone with more knowledge in the area has to say about particle size testing, as well as the information Dr. Krauss shares both about the etiology of atherosclerosis and the significance of "small dense" LDL particle count vs the standard LDL measure on a lipid panel, particularly for people with borderline risk of CVD. To his credit, Dr. Krauss acknowledges that particle testing isn't for everyone. People at either extreme (i.e. very low or very high LDL cholesterol) probably don't need it - for obvious and opposite reasons. It's only in the borderline cases, like my family member, where it might be helpful. He also said the standard heart attack risk calculators, which don't take into account anything about particle size, do a pretty good job, and particle size and counts doesn't add very much to their accuracy / predictive power. But he sticks by idea that mechanistically, it's the small dense LDL particles that matter most for CVD risk. He also talks about how statins do work, but don't work as well as you might think because they upregulate the liver's LDL-receptor, which is pretty ineffective at clearly the most atherogenic particles - the small dense ones. He talks about statin side effects (muscle pain / weakness, but especially increased risk of diabetes, particularly in women). He is very much in favor of diet and lifestyle interventions to manage CVD risk, but as a researcher and clinician, he says there is trouble both proving the benefits of diet/lifestyle on CVD risk in clinical trials, and convincing his patients to adopt diet and lifestyle modifications, due both to compliance issues, and also in terms of getting the funding to do the research to make a convincing case. He says it's much easier to both get funding for, and to conduct, research on statins and other pharmacological interventions, because there is money to be made, and compliance is much less of an issue. Whether or not Dr. Krauss is blowing smoke about the value of particle size testing, it seemed to my (admittedly relatively naive) ears that Rhonda had a good set of questions and Dr. Krauss had clear and well thought out set of answers. For anyone interested in the topic, check out the show notes below and give it a watch/listen and let us know what you think. --Dean Begin Show Notes ============== Dr. Ronald Krauss on LDL Cholesterol, Particle Size, Heart Disease & Atherogenic Dyslipidemia In this podcast, I interview my friend and colleague Dr. Ronald Krauss. Ronald Krauss, M.D. is the director of atherosclerosis research at Children’s Hospital Oakland Research Institute, Adjunct Professor at UCSF and UC Berkeley. Dr. Krauss is really one of the pioneering scientists that changed the way we all think about cholesterol and saturated fat. The work of Dr. Krauss has demonstrated that smaller, denser LDL particles, which he pioneered a test for, known as the "Ion Mobility" test, has special significance when it comes to determining risk of heart disease. Regrettably, this test is not yet universally employed in a clinical setting in the manner in which total LDL cholesterol is, however. This test is called Cardio IQ® Lipoprotein Fractionation, Ion Mobility and is offered by quest diagnostics. Dr. Krauss is responsible for having played a part in the actual guidelines used by the American Heart Association in his role as chairman of the Nutrition Committee. Additionally, Dr. Krauss has also served on both the Committee on Dietary Recommended Intakes for Macronutrients and the Committee on Biomarkers of Chronic Disease of the Institute of Medicine of the National Academy of Sciences. In this podcast, Ron and I discuss what HDL and LDL cholesterol are, what they do in the body and how they play a role in heart disease. We talk about what small, dense LDL particles are, how they form, what effect eating saturated fat versus refined carbohydrates have on LDL particle size and heart disease risk and more generally what the main risk factors for heart disease are. Ron also talks about the good, bad and the ugly of LDL-lowering drugs known as statins and much more. In this conversation, Ron and I discuss... Changes in the availability of funding for good nutritional research."It's a fact that NIH, which is the major funder of biomedical research in the world, has basically pulled the plug on clinical research support as a general area of emphasis. The infrastructure for doing good nutritional studies, in particular, has relied on a mechanism that is now being withdrawn." - Dr. Ronald M Krauss The important difference between consumption of dietary cholesterol, which has a negligible influence on heart disease risk, and cholesterol produced endogenously in the body (which can be a marker of risk, depending on a complete profile). The good, bad and the ugly of LDL-lowering drugs known as statins and much more. What differentiates fructose from fruit versus fructose as an added sugar, namely: speed of absorption, presence or absence of other beneficial compounds (fiber, micronutrients, polyphenols, etc.), and differences in dose. How LDL (low-density lipoprotein), and particularly the ApoB protein inside of LDL, is needed to transport cholesterol, triglycerides, and fatty acids throughout the bloodstream in order to deliver them to other tissues in the body that may need them. What small, dense LDL particles are, how they form, what effect eating saturated fat versus refined carbohydrates have on LDL particle size and heart disease risk and more generally what the main risk factors for heart disease are. The functional difference between large, buoyant LDL particles and small, dense LDL particles and introduces us to the traits of what he terms "atherogenic dyslipidemia." These traits consist of: High levels of small, dense LDL cholesterol. Low levels of HDL cholesterol. High levels of triglyceride-rich lipoproteins (very-low-density lipoproteins or "VLDL") and their remnants. How small, dense LDL particles increase the risk of atherosclerosis. There is only one ApoB protein per LDL particle, which is what enables ApoB to be a surrogate blood biomarker for LDL particle number. How access to the ApoB protein can become obscured due to conformation changes in the small, dense LDL particles. As the size of the particle decreases, this conformation change reduces the ability for the particle to bind to the LDL receptor and be recycled by the liver. How VLDL particles, the precursor to LDL, demonstrate an interaction with LPS (also known as endotoxin, a component of bacterial cell membranes), and how it's possible that some of the negative associations with this particle size may be a result of their simply being in the blood stream longer: this gives them a greater opportunity to undergo inflammatory transformations.This part is especially exciting to me because it may be an interesting link by which gut health (where much of the bacteria and immune cells in the body are located) and the importance of controlling inflammation to cardiovascular health. How saturated fat appears to increase the larger, more buoyant LDL particles, which do not have the same robust correlation to heart disease risk that the smaller, more dense particles do. Dr. Krauss also takes the stance that consumption of saturated fat does not have as strong of a link to heart disease risk as previously suggested by others, and may be less relevant except in the case of what he termed "hyper-responders." These "hyper-responders" have gene polymorphisms that cause them to respond differently to saturated fat. How increased carbohydrate consumption, especially simple sugars may have been an unintended consequence of the push for low-fat diets, and how this increased traits associated with atherogenic dyslipidemia: namely, a shift from the larger, more buoyant LDL particles to the smaller, more dense LDL particles. Broadly, the differences between the various types of lipoprotein particles, including very-low-density lipoproteins (VLDL), and high-density lipoprotein (HDL) and what their roles are in the body. This really is one of the better science-based podcasts I've posted to date. It's often a bit nuanced, but hopefully with the help of some of the annotations in the video you will find it as enriching as I have. Dr. Krauss is a real pioneer in the field and drops huge amounts of knowledge, so go check it out now! ============== End Show Notes
  8. All, The benefits of yoga has been discussed on various threads lately, so I figured it was time to consolidate the discussions into a single master thread, particularly since there is a new study I wanted to post (see below). First we saw in this thread that yoga beats both walking and a mediterranean diet for CVD risk reduction. Then we saw in this post by Cloud that 12 weeks of yoga reduces inflammatory markers in recovering cancer patients. Now, a new study [1] (popular press story) found that 12 weeks of yoga beat out the "gold standard" memory training technique in people with mild cognitive impairment. The yoga group had lower depression scores, and improved verbal and visuospatial memory compared with memory training. While the study was small, its effects were pretty impressive, and were accompanied by changes in brain region connectivity as measured by FMRI brain scans. With all this evidence of benefit, it seems like a good idea to start practicing yoga, and consider having the next CR Conference at a yoga center like Saul suggests - maybe Sthira and Saul can teach the rest of us! --Dean ---------- [1] J Alzheimers Dis. 2016 Apr 5;52(2):673-84. doi: 10.3233/JAD-150653. Changes in Neural Connectivity and Memory Following a Yoga Intervention for Older Adults: A Pilot Study. Eyre HA(1,)(2), Acevedo B(1), Yang H(1), Siddarth P(1), Van Dyk K(1), Ercoli L(1), Leaver AM(3), Cyr NS(1), Narr K(3), Baune BT(2), Khalsa DS(4), Lavretsky H(1). Author information: (1)Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA. (2)Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia. (3)Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, UCLA, Los Angeles, CA, USA. (4)Alzheimer's Research and Prevention Foundation, Tucson, AZ, USA. BACKGROUND: No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity. OBJECTIVES: This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI). METHODS: Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active "gold-standard" control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance. RESULTS: Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex. CONCLUSION: Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies. PMID: 27060939
  9. Sthira, you'll love this one [1] posted by Al Pater (thanks Al!) to the CR email list. It compared various group lifestyle interventions, including yoga, walking, Mediterranean diet and group smoking cessation classes for their effect over the following 10 years on risk of cardiovascular disease. It found: [Y]oga was associated with the largest 10-year cardiovascular disease risk reductions (maximum absolute reduction 16.7% for the highest-risk individuals). Walking generally ranked second (max 11.4%), followed by Mediterranean diet (max 9.2%), and group therapy for smoking (max 1.6%). Of course, the effectiveness of a treatment is dependent on subject compliance and treatment efficacy. That's why smoking cessation treatments were almost completely ineffective - almost nobody quits for very long. The authors acknowledge this, saying: We have presented a rank order of strategies that do not include taking any pills or medication. As such, non-adherence with lifestyle change and other health behaviors, including pill-taking, is of concern and may dilute intervention effects. Our calculations are based on intention to-treat rates from the clinical trials, which incorporate non-adherence. For a current smoker, successfully quitting smoking is the most effective lifestyle change. Smoking cessation is, however, difficult to achieve and group therapy for stopping smoking has only a small probability of success. From an intention-to-treat perspective, if yoga is as effective as reported in currently published meta-analyses, then yoga could be considered among the strongest lifestyle interventions for reducing CVD risk. Too bad they didn't include a dance intervention group. Based on the benefits of dance discussed here, I bet it might have done best of all! --Dean ---------- [1] Comparative Effectiveness of Personalized Lifestyle Management Strategies for Cardiovascular Disease Risk Reduction. Chu P, Pandya A, Salomon JA, Goldie SJ, Hunink MG. J Am Heart Assoc. 2016 Mar 29;5(3). pii: e002737. doi: 10.1161/JAHA.115.002737. PMID: 27025969 Free Article http://jaha.ahajournals.org/content/5/3/e002737.full http://jaha.ahajournals.org/content/5/3/e002737.full.pdf+html Abstract BACKGROUND: Evidence shows that healthy diet, exercise, smoking interventions, and stress reduction reduce cardiovascular disease risk. We aimed to compare the effectiveness of these lifestyle interventions for individual risk profiles and determine their rank order in reducing 10-year cardiovascular disease risk. METHODS AND RESULTS: We computed risks using the American College of Cardiology/American Heart Association Pooled Cohort Equations for a variety of individual profiles. Using published literature on risk factor reductions through diverse lifestyle interventions-group therapy for stopping smoking, Mediterranean diet, aerobic exercise (walking), and yoga-we calculated the risk reduction through each of these interventions to determine the strategy associated with the maximum benefit for each profile. Sensitivity analyses were conducted to test the robustness of the results. In the base-case analysis, yoga was associated with the largest 10-year cardiovascular disease risk reductions (maximum absolute reduction 16.7% for the highest-risk individuals). Walking generally ranked second (max 11.4%), followed by Mediterranean diet (max 9.2%), and group therapy for smoking (max 1.6%). If the individual was a current smoker and successfully quit smoking (ie, achieved complete smoking cessation), then stopping smoking yielded the largest reduction. Probabilistic and 1-way sensitivity analysis confirmed the demonstrated trend. CONCLUSIONS: This study reports the comparative effectiveness of several forms of lifestyle modifications and found smoking cessation and yoga to be the most effective forms of cardiovascular disease prevention. Future research should focus on patient adherence to personalized therapies, cost-effectiveness of these strategies, and the potential for enhanced benefit when interventions are performed simultaneously rather than as single measures. KEYWORDS: cardiovascular risk reduction; comparative effectiveness; lifestyle modification
  10. All, Sthira, in a recent post to the exercise thread ,which I wantonly edited (my bad, sorry Sthira...) in order to create this new thread on animal cruelty, mentioned how beneficial dance is for health & longevity, complementing my daughter, who is a dancer. In vindication Sthira's assessment, this new study [1] (press release, popular press article) found that engaging in social dancing, particularly rigorous social dancing (enough to make one "out of breath and sweaty"), reduced cardiovascular mortality risk by 50% relative to people who didn't dance. Dancing was about twice as beneficial for CVD mortality as walking, even after controlling for a pretty extensive set of potential confounders, including age, sex, socioeconomic status, smoking, alcohol, BMI, chronic illness, psychosocial distress, and total physical activity amount. Discussing the study, one of the authors said: "We should not underestimate the playful social interaction aspects of dancing which, when coupled with some more intense movement, can be a very powerful stress relief and heart health promoting pastime... The Bee Gees said it best - you should be dancing," Maybe we should have a dance party one evening at the CR Conference.☺ --Dean ---------- [1] American Journal of Preventive Medicine Available online 1 March 2016, DOI: http://dx.doi.org/10.1016/j.amepre.2016.01.004 Dancing Participation and Cardiovascular Disease Mortality: A Pooled Analysis of 11 Population-Based British Cohorts Dafna Merom, PhD, Ding Ding, PhD, Emmanuel Stamatakis, PhD Free full text: http://www.ajpmonline.org/article/S0749-3797(16)00030-1/pdf Abstract Introduction Little is known about whether cardiovascular benefits vary by activity type. Dance is a multidimensional physical activity of psychosocial nature. The study aimed to examine the association between dancing and cardiovascular disease mortality. Methods A cohort study pooled 11 independent population surveys in the United Kingdom from 1995 to 2007, analyzed in 2014. Participants were 48,390 adults aged ≥40 years who were free of cardiovascular disease at baseline and consented to be linked to the National Death Registry. Respondents reported participation in light- or moderate-intensity dancing and walking in the past 4 weeks. Physical activity amount was calculated based on frequency, duration, and intensity of participation in various types of exercise. The main outcome was cardiovascular disease mortality based on ICD-9 codes 390−459 or ICD-10 codes I01−I99. Results During 444,045 person-years, 1,714 deaths caused by cardiovascular disease were documented. Moderate-intensity, but not light-intensity, dancing and walking were both inversely associated with cardiovascular disease mortality. In Cox regression models, the hazard ratios for cardiovascular disease mortality, adjusted for age, sex, SES, smoking, alcohol, BMI, chronic illness, psychosocial distress, and total physical activity amount, were 0.54 (95% CI=0.34, 0.87) for moderate-intensity dancing and 0.75 (95% CI=0.62, 0.90) for moderate-intensity walking. Conclusions Moderate-intensity dancing was associated with a reduced risk for cardiovascular disease mortality to a greater extent than walking. The association between dance and cardiovascular disease mortality may be explained by high-intensity bouts during dancing, lifelong adherence, or psychosocial benefits.
  11. Dean Pomerleau

    Let the sun shine in

    Admin Note: I'm moving this post by Al to the other thread where this study about sun exposure and longevity has already begun.
  12. There is a really interesting new meta-analysis [1] in this week's issue of The Lancet on the association between height and health/longevity. Here is a popular press article on the study, with the title Big And Tall: Nutritious Meals May Make Us Taller But They Could Also Increase Our Cancer Risk. The researchers looked at 121 epidemiological studies of over a million people that assessed the association of height with health and lifespan. The heart of the paper are these two graphs: showing how in both men and women, being taller reduces risk of coronary heart disease, but increases risk of cancer. Here is a graphical representation of the over/undernutrition-based mechanisms the authors postulate to explain the observations: The link to cancer via higher insulin in people who eat a lot (and hence grow taller) is familiar. What was a bit surprising was their suggestion that increased levels of grow factors like IGF-1 in taller people may actually improve insulin sensitivity and hence reduce diabetes and cardiovascular disease. --Dean ------------- [1] The Lancet Diabetes & Endocrinology Available online 28 January 2016 DOI: http://dx.doi.org/10.1016/S2213-8587(15)00474-X| Divergent associations of height with cardiometabolic disease and cancer: epidemiology, pathophysiology, and global implications Norbert Stefan, MD, Hans-Ulrich Häring, MD, Frank B Hu, MD, Dr Matthias B Schulze, DrPHcorrespondenceemail Full text: http://dx.doi.org.sci-hub.io/10.1016/S2213-8587(15)00474-X Summary Among chronic non-communicable diseases, cardiometabolic diseases and cancer are the most important causes of morbidity and mortality worldwide. Although high BMI and waist circumference, as estimates of total and abdominal fat mass, are now accepted as predictors of the increasing incidence of these diseases, adult height, which also predicts mortality, has been neglected. Interestingly, increasing evidence suggests that height is associated with lower cardiometabolic risk, but higher cancer risk, associations supported by mendelian randomisation studies. Understanding the complex epidemiology, biology, and pathophysiology related to height, and its association with cardiometabolic diseases and cancer, is becoming even more important because average adult height has increased substantially in many countries during recent generations. Among the mechanisms driving the increase in height and linking height with cardiometabolic diseases and cancer are insulin and insulin-like growth factor signalling pathways. These pathways are thought to be activated by overnutrition, especially increased intake of milk, dairy products, and other animal proteins during different stages of child development. Limiting overnutrition during pregnancy, early childhood, and puberty would avoid not only obesity, but also accelerated growth in children—and thus might reduce risk of cancer in adulthood.
  13. All, Testosterone (T) and other sex hormone levels have always been a topic of interest and concern to CR practitioners. Some men (like me) report dramatically reduced T levels, down to levels not typically seen in any men except the very elderly. Others seem to maintain their T at fairly normal levels for their age. So which is better? On the one hand, low testosterone has sometimes been considered a CR "badge of courage" (among men anyway) - indicating one is practicing serious CR, and a positive reflection of the body trading off fecundity for upregulation of maintenance & repair functions (similar to low IGF-1). Women live longer than men across cultures, which some attribute to differences in T level, and eunuchs have been found to live longer, by as much as 15-20 years [2]! On the other hand, low T often (but not always) has a dramatic effect on libido, and one's overall aggressive drive to succeed / accomplish things. On the health side, negative health outcomes are frequently associated with hypogonadism (low T) in men, including bone health issues [4], sarcopenia [4], cognitive decline [5], and an increased risk of cardiovascular disease. Regarding the latter, some studies (e.g. see [3] for review) have found T supplementation in hypogonadal men reduces cardiovascular disease risk, but the effect may be limited to obese men with metabolic syndrome, or may result from pharmaceutical industry bias in T supplementation trials [6]. Interestingly, this meta-analysis [6] found that in trials not sponsored by Big Pharma, CVD risk was increased among men receiving supplemental T (OR 2.06, 95% CI 1.34 to 3.17). So overall, the relationship between the low T that many serious male CR practitioners exhibit and our long-term health & longevity remains an open question. Moreover, hypogonadism in the general population is typically associated with obesity and metabolic syndrome, obviously a very different etiology than hypogonadism in CR practitioners, making the picture even more muddled... So I reacted with interest, but also some trepidation, when I saw Al Pater post this new study [1] (thanks Al!), on the association of T and other sex hormones with all-cause, cancer and cardiovascular mortality in men. So let's dive in. First off, this was not a supplementation trial - they measured the natural levels of T, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Sex Hormone Binding Globulin (SHBG), free testosterone (FT), and estradiol (E) and in 5300 men of all ages and followed them for an average of 18.5 years to see how many died, from what causes, and how their deaths were associated with these sex hormones. Here are some interesting statistics at baseline, from the free full text Table 1 (see below): As expected, T and FT was lower in older men, whereas LH, FSH, and SHBG increased. Interestingly, smokers had higher T, FT, LH, FSH, E and SHBG than non-smokers at baseline. Exercise, and particular "competitive sport" participation, was associated with increased T, FT, and lower LH. Could be reverse causality - people with high T are more aggressive and therefore more likely to be attracted to competitive sports... Overweight and obese men had dramatically lower T and FT at baseline - which will be important later. Here is the baseline data for sex hormones by demographics for anyone interested in the details (click to enlarge): Now the interesting part - the mortality results (some of which comes from the text of the supplemental material). First for cancer mortality: There was a between-quartile trend towards increased cancer mortality with higher T, but the differences was only really significant in smokers in the highest quartile of T (OR 1.53, 95%CI: 1.14 – 2.08). In non-smokers, T and FT had virtually no impact on cancer mortality. But there was a pretty strong trend towards more cancer with higher levels of LH and FSH. Keep an eye on LH in particular, it will be important later... And now, CVD mortality: Men with total testosterone levels in the highest quartile had a reduced risk of CVD mortality compared to men in the lowest quartile (HR 0.72, 95% CI: 0.53– 0.98). The same relationship held for FT. It is looking bad for us hypogonadal CRers... But this increased CVD risk with low T (and FT) was in the fully-adjusted model, which included factoring out BMI from the analysis (recall overweight/obese men had dramatically lower T and FT at baseline). In a model that adjusted for waist circumference instead of BMI, and especially in a model that adjusted for # of markers of metabolic syndrome, the increased risk of CVD with lower T and FT dropped dramatically to the point of no longer being significant between the highest and lowest quintiles of T = (OR 0.66, 95%CI: 0.38-1.16). In other words, to first approximations, if you ignore low T and FT resulting from (or associated with) metabolic syndrome, the association between low T (and FT) and increased CVD goes away... And now, the all-important All-cause mortality: There was no significant differences in all-cause mortality across age-standardized quartiles of T (OR 1.01, 95%CI: 0.87-1.18) - to some degree higher cancer risk and lower CVD risk with higher T offset each other, so all-cause mortality was a wash with higher T. The same lack of significant mortality effect was seen for inter-quartile comparison of FT (OR 0.87, 95%CI: 0.75-1.00), but when the trend from lowest to highest quartile of FT was considered, lower FT was associated with increased all-cause mortality (p for trend < 0.02). Again, looking (somewhat) bad for hypogonadal CRers... An increased all-cause mortality was seen for men in the highest (vs. lowest) quartiles of LH and estradiol, (HR 1.32, 95% CI: 1.14 –1.53) and (HR 1.23, 95% CI: 1.06 –1.43), respectively. If you are confused by now, perhaps this graphical depiction of the major study findings for all-cause and CVD mortality (with my color highlights) will help (click to enlarge): As you can see, if we focus on all-cause mortality, higher SHBG, higher LH, and lower FT are associated with increased risk. So what the heck does all this mean?!?! Here is my take on it, basically paraphrasing the authors' discussion / speculation. Obesity, and especially metabolic syndrome, are associated with increased mortality risk, and reduced T and FT levels. It may therefore be that low T (& FT) is a marker for impaired androgen signalling in men with metabolic syndrome - i.e. their sex-hormone signalling is messed up, just like some of their other pathways (e.g. insulin signalling) are messed up by all the fat they are carrying. As a result, their LH is elevated - i.e. the "captain" is asking (via increased LH) the "engine room" (i.e. Leydig cells) to produce more T, but the Leydig cells aren't up to the task perhaps because they are gummed up with fat, so T remains low despite elevated LH calling for more. This could be similar in some respects to diabetes, in which insulin doesn't work to clear glucose because of fat so the body calls for the pancreas to produce more, and eventually the beta cells in the pancreas give up the ghost and can't make enough insulin to clear blood glucose. So what does this mean for CR practitioners? In us, T is low on purpose from the body's perspective (if I may speak teleologically) - as indicated by our low LH levels (my bloodwork shows my LH to always be near or below the low end of the RR since starting CR). In other words, rather than T being low because the body can't/won't make it (as is the case in guys with metabolic syndrome), our T is low because our body doesn't need or want it. Again it is perhaps a story similar to IGF-1 and insulin. We (hopefully) have low fasting insulin not because our beta cells are messed up and can't make it (like in late-stage diabetes resulting from metabolic syndrome), but because our bodies don't need/want much insulin - we've got enough insulin to clear the modest amount of glucose we have to process, especially since our insulin sensitivity remains high. So in short, our low T and low FT may reflect an entirely different, (hopefully) healthier state to be in than having low T and FT as a result of metabolic syndrome. But then again, that might be just wishful thinking. In particular, our low T and FT may be "intentional" on the part of our body and it may not be good for us in the long run. In other words, our bodies may be hunkering down to survive the (self-induced) famine by lowering T and FT, but in the process sacrificing "non-critical" systems like muscle mass, bone health, and cognitive function - systems that apparently benefit downstream from higher levels of testosterone. It seems it could go either way. But in any case, we're unlikely to be in as bad shape along these dimensions as men who have low T and FT as a result of metabolic syndrome. I hope this has done more to clarify than confuse. But re-reading, I'm not so sure... --Dean ---------- [1] J Clin Endocrinol Metab. 2015 Oct 21:jc20152460. [Epub ahead of print] The association of reproductive hormone levels and all-cause, cancer and cardiovascular disease mortality in men. Agergaard Holmboe S, Vradi E, Kold Jensen T, Linneberg A, Husemoen LL, Scheike T, Skakkebæk NE, Juul A, Andersson AM. Full Text: http://press.endocrine.org/doi/pdf/10.1210/jc.2015-2460 Abstract CONTEXT: Testosterone levels (T) have been associated with mortality, but controversy exists. OBJECTIVE: To investigate associations between serum levels of total testosterone, SHBG, free testosterone, estradiol, LH and FSH, and subsequent mortality with up to 30 years of follow-up. DESIGN: A prospective cohort study consisting of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with complete registry follow-up. SETTING AND PARTICIPANTS: 5,350 randomly selected men from the general population aged 30, 40, 50, 60 or 70 years at baseline. MAIN OUTCOME MEASURES: All-cause mortality, cardiovascular disease (CVD) mortality and cancer mortality. RESULTS: 1,533 men died during the follow-up period; 428 from CVD and 480 from cancer. Cox proportional hazard models revealed that men in highest LH quartile had an increased all-cause mortality compared to lowest quartile (HR=1.32, 95%CI: 1.14 to 1.53). Likewise, increased quartiles of LH/T and estradiol increased the risk of all-cause mortality (HR=1.23, 95%CI: 1.06 to 1.43, HR=1.23, 95%CI: 1.06 to 1.43). No association to testosterone levels was found. Higher LH levels were associated with increased cancer mortality (HR=1.42, 95%CI: 1.10 to 1.84) independently of smoking status. Lower CVD mortality was seen for men with testosterone in the highest quartile compared to lowest (HR=0.72, 95%CI: 0.53 to 0.98). Furthermore, negative trends were seen for SHBG and free testosterone in relation to CVD mortality, however insignificant. CONCLUSION: The observed positive association of LH and LH/T, but not testosterone, with all-cause mortality suggests that a compensated impaired Leydig cell function may be a risk factor for death by all causes in men. Our findings underpin the clinical importance of including LH measurement in the diagnostic work-up of male patients seeking help for possible androgen insufficiency. PMID: 26488309 ------------ [2] Curr Biol. 2012 Sep 25;22(18):R792-3. doi: 10.1016/j.cub.2012.06.036. The lifespan of Korean eunuchs. Min KJ, Lee CK, Park HN. Free Full Text: http://www.cell.com/current-biology/abstract/S0960-9822(12)00712-9 Abstract Although many studies have shown that there are trade-offs between longevity and reproduction, whether such trade-offs exist in humans has been a matter of debate [1,2] . In many species, including humans, males live shorter than females, which could be due to the action of male sex hormones. Castration, which removes the source of male sex hormones, prolongs male lifespan in many animals, but this issue has been debated in humans [3] . To examine the effects of castration on longevity, we analyzed the lifespan of historical Korean eunuchs. Korean eunuchs preserved their lineage by adopting castrated boys. We studied the genealogy records of Korean eunuchs and determined the lifespan of 81 eunuchs. The average lifespan of eunuchs was 70.0 ± 1.76 years, which was 14.4–19.1 years longer than the lifespan of non-castrated men of similar socio-economic status. Our study supports the idea that male sex hormones decrease the lifespan of men. PMID: 23017989 -------------- [3] Expert Opin Drug Saf. 2014 Oct;13(10):1327-51. doi: 10.1517/14740338.2014.950653. Epub 2014 Aug 19. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Corona G(1), Maseroli E, Rastrelli G, Isidori AM, Sforza A, Mannucci E, Maggi M. Author information: (1)Azienda-Usl Bologna, Maggiore-Bellaria Hospital, Medical Department, Endocrinology Unit , Bologna , Italy. INTRODUCTION: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events. AREAS COVERED: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed. EXPERT OPINION: The present systematic review and meta-analysis does not support a causal role between TS and adverse CV events. Our results are in agreement with a large body of literature from the last 20 years supporting TS of hypogonadal men as a valuable strategy in improving a patient's metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease. PMID: 25139126 --------------- [4] Clin Endocrinol (Oxf). 2005 Sep;63(3):280-93. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Isidori AM(1), Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Author information: (1)Cattedra di Andrologia, Universita 'La Sapienza', Rome, Italy. andrea.isidori@uniroma1.it OBJECTIVES: Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. DATA SOURCE: A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. REVIEW METHODS: Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. RESULTS: Overall, 1,083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64.5 years (range 49.9--77.6) and mean serum testosterone was 10.9 nmol/l (range 7.8--19). Testosterone treatment produced: (i) a reduction of 1.6 kg (CI: 2.5--0.6) of total body fat, corresponding to -6.2% (CI: 9.2--3.3) variation of initial body fat, (ii) an increase in fat free mass of 1.6 kg (CI: 0.6--2.6), corresponding to +2.7% (CI: 1.1--4.4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size=0.3 standard mean difference (SMD), CI: -0.0 to 0.6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3.7% (CI: 1.0--6.4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = -0.6 SMD, CI: -1.0 to -0.2). Testosterone also reduced total cholesterol by 0.23 mmol/l (CI: -0.37 to -0.10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003). Sensitivity and meta-regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. CONCLUSION: The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems. PMID: 16117815 ------------- [5] Mol Neurobiol. 2015 Jul 8. [Epub ahead of print] Low Testosterone Level and Risk of Alzheimer's Disease in the Elderly Men: a Systematic Review and Meta-Analysis. Lv W(1), Du N(1), Liu Y(1), Fan X(1), Wang Y(1), Jia X(2), Hou X(3), Wang B(4). Sex steroids can positively affect the brain function, and low levels of sex steroids may be associated with worse cognitive function in the elderly men. However, previous studies reported contrary findings on the relationship between testosterone level and risk of Alzheimer's disease in the elderly men. The objective of this study was to comprehensively assess the relationship between low testosterone level and Alzheimer's disease risk in the elderly men using a meta-analysis. Only prospective cohort studies assessing the influence of low testosterone level on Alzheimer's disease risk in elderly men were considered eligible. Relative risks (RRs) with 95 % confidence intervals (95 % CI) were pooled to assess the risk of Alzheimer's disease in elderly men with low testosterone level. Seven prospective cohort studies with a total of 5251 elderly men and 240 cases of Alzheimer's disease were included into the meta-analysis. There was moderate degree of heterogeneity among those included studies (I (2) = 47.2 %). Meta-analysis using random effect model showed that low plasma testosterone level was significantly associated with an increased risk of Alzheimer's disease in elderly men (random RR = 1.48, 95 % CI 1.12-1.96, P = 0.006). Sensitivity analysis by omitting one study by turns showed that there was no obvious change in the pooled risk estimates, and all pooled RRs were statistically significant. This meta-analysis supports that low plasma testosterone level is significantly associated with increased risk of Alzheimer's disease in the elderly men. Low testosterone level is a risk factor of worse cognitive function in the elderly men. PMID: 26154489 ------------- [6] BMC Med. 2013 Apr 18;11:108. doi: 10.1186/1741-7015-11-108. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. Xu L(1), Freeman G, Cowling BJ, Schooling CM. Author information: (1)School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China. Comment in Evid Based Med. 2014 Feb;19(1):32-3. BACKGROUND: Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. METHODS: A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using "("testosterone" or "androgen") and trial and ("random*")" with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. RESULTS: Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). CONCLUSIONS: The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy. PMID: 23597181
  14. All, It looks like an apple a day helps keep the grim reaper away, at least in elderly women according to this new study [1] shared by Al Pater (thanks Al!). Researchers followed 1500 Australian women for 15 years, assessing their intake of various fruits every few years. Over the years their reported intake of apples and other fruits remained quite stable. The authors focused on the four fruits that made up the bulk (75%) of total fruit consumption - apples (20%), pears (11%), citrus fruit (23%), & bananas (21%). They found that women who ate more than 100g of apple per day (for reference, an average medium apple weighs 182g) had a 35% lower risk of all-cause mortality during the follow-up period, even after adjusting for a bunch of potential confounders, including age, BMI, smoking status, socio-economic status, diabetes, CVD, cancer, use of antihypertensive medication, use of cholesterol-lowering medication, use of low-dose aspirin, physical activity, energy intake and alcohol intake. Here are a couple interesting figures from the full text (available from Al). First, a needle plot of morality for the different fruits and causes of death: As you can see, pears and especially citrus weren't all that great for mortality. But apples, bananas and total fruit were all beneficial. Interestingly, bananas were the best of all these fruit for cardiovascular mortality, perhaps because of the important role potassium plays in CVD risk [2]. The one reservation/caveat I can see is that higher apple intake is associated with lots of other markers for an overall healthy diet, as you can see from this figure: Women who ate a lot of apples also ate (not surprisingly) a lot more fiber, flavonoids, total fruit etc. Although the authors didn't report on it, I suspect they also probably ate more vegetables, less trans and saturated fat, etc. So while apples are certainly healthy, they may also be an indicator of an overall healthy diet and lifestyle, and therefore not the (entire) cause of reduced mortality in these women. --Dean -------------- [1] Apple intake is inversely associated with all-cause and disease-specific mortality in elderly women. Hodgson JM, Prince RL, Woodman RJ, Bondonno CP, Ivey KL, Bondonno N, Rimm EB, Ward NC, Croft KD, Lewis JR. Br J Nutr. 2016 Mar;115(5):860-7. doi: 10.1017/S0007114515005231. Epub 2016 Jan 20. Abstract Higher fruit intake is associated with lower risk of all-cause and disease-specific mortality. However, data on individual fruits are limited, and the generalisability of these findings to the elderly remains uncertain. The objective of this study was to examine the association of apple intake with all-cause and disease-specific mortality over 15 years in a cohort of women aged over 70 years. Secondary analyses explored relationships of other fruits with mortality outcomes. Usual fruit intake was assessed in 1456 women using a FFQ. Incidence of all-cause and disease-specific mortality over 15 years was determined through the Western Australian Hospital Morbidity Data system. Cox regression was used to determine the hazard ratios (HR) for mortality. During 15 years of follow-up, 607 (41·7 %) women died from any cause. In the multivariable-adjusted analysis, the HR for all-cause mortality was 0·89 (95 % CI 0·81, 0·97) per sd (53 g/d) increase in apple intake, HR 0·80 (95 % CI 0·65, 0·98) for consumption of 5-100 g/d and HR 0·65 (95 % CI 0·48, 0·89) for consumption of >100 g/d (an apple a day), compared with apple intake of <5 g/d (P for trend=0·03). Our analysis also found that higher apple intake was associated with lower risk for cancer mortality, and that higher total fruit and banana intakes were associated lower risk of CVD mortality (P<0·05). Our results support the view that regular apple consumption may contribute to lower risk of mortality. Key words Apples; Fruits; All-cause mortality; Disease-specific mortality; CVD; Cancer PMID: 26787402 -------------- [2] J Clin Hypertens (Greenwich). 2002 May-Jun;4(3):198-206. Importance of potassium in cardiovascular disease. Sica DA(1), Struthers AD, Cushman WC, Wood M, Banas JS Jr, Epstein M. Author information: (1)Section of Clinical Pharmacology and Hypertension, Division of Nephrology, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA 23298, USA. dsica@hsc.vcu.edu The pivotal role of potassium (K+) in cardiovascular disease and the importance of preserving potassium balance have become clinical hot points, particularly as relates to new and emerging cardioprotective and renoprotective therapies that promote potassium retention. Although clinicians may be aware of the critical nature of this relationship, quite frequently there is some uncertainty as to the best way to monitor potassium levels in the face of a host of pathologic states and/or accompanying drug therapies that affect serum levels and/or total body potassium balance. Moreover, guidelines for monitoring of serum potassium levels are at best tentative and oftentimes are translated according to the level of concern of the respective physician. To address these uncertainties, an expert group was convened that included representatives from multiple disciplines. They attempted to reach consensus on the importance of K+ in hypertension, stroke, and arrhythmias as well as practical issues on maintaining K+ balance and avoiding K+ depletion. Because of the complexity of this topic, issues of hyperkalemia will be addressed in a forthcoming manuscript. Copyright 2002 Le Jacq Communications, Inc. PMID: 12045369
  15. All, Anyone who has been following discussions around here will realize that I've been criticizing salmon as a healthy food, and Saul has been vehemently defending it, which has lead to some amusing exchanges, e.g. here, here and especially here, where Saul wrote: Well, the evidence just keeps piling up against Saul's sacred cow, er, fish. Background Summary: PCBs are bad sh*t. PCBs (or polychlorinated biphenyls) are man-made organic chemicals widely manufactured and used in a variety of industries, but mostly for cooling and insulating fluid for electrical devices, all over the world up until 1979 when they were banned. Unfortunately, PCBs are very persistent, remaining in the water and soil for many years, and bioaccumulating the in flesh (mostly fat) of animals. Fish, especially fatty fish, seems to be the food in the human diet where the most PCBs bioaccumulate, as illustrated by this graph (data from [2]) of PCB content in 12,000+ food samples from around Europe: Notice that fish oil is off the chart, but people typically only consume a gram or two of FO per day, and this graph represents micrograms per kilograms. Fish itself (all types) was about 5x higher than any other animal products. Fruit, vegetables and cereals had close to zero PCBs. Interestingly though, most exposure in North America comes from beef, dairy and other animal flesh rather than fish, since we eat so much more of them than fish: So how bad are PCBs? Pretty bad across the board, including causing cancer, endocrine disruption, reproductive and neurological effects. See here for more details about all the bad effects PCBs have on human health. With that background, this new study [1] posted by Al (thanks Al!) looked at dietary PCBs levels based on self-reported food-frequency questionnaires from ~36,000 elderly Swedish women, and then followed them for an average of 12 years to see how heart attack risk related to dietary PCB exposure. First, off a helpful chart of demographics of study participants by quartile of dietary PCB intake: As you can see from my highlights, the dietary PCB (and mercury) levels in these women was strongly correlated with fish and long-chain omega-3 intake. Women who ate the most fish had almost 3x the level of PCBs of those who ate the least. So what about heart attacks? Here is what the authors' found: Women in the highest quartile of dietary PCB exposure (median 286 ng/day) had a multivariable-adjusted RR of myocardial infarction of 1.21 (95% confidence interval [CI], 1.01–1.45) compared to the lowest quartile (median 101 ng/day) before, and 1.58 (95% CI, 1.10–2.25) after adjusting for EPA-DHA. Stratification by low and high EPADHA intake, resulted in RRs 2.20 (95% CI, 1.18–4.12) and 1.73 (95% CI, 0.81–3.69), respectively comparing highest PCB tertile with lowest. The intake of dietary EPA-DHA was inversely associated with risk of myocardial infarction after but not before adjusting for dietary PCB. In other words, having the highest intake of PCBs (mostly from fish) was associated with a 21% increase in the risk of heart attack relative to being in the lowest PCB intake group. But it was only a 21% increase because EPA/DHA was pulling the other way, helping to prevent heart attacks. If you statistically factor out the EPA/DHA benefits, PCBs alone would raise heart attack risk by 58% in the top vs. bottom quartile group. Analyzed the other way, EPA/DHA intake wasn't associated with fewer heart attacks, largely because of the PCBs that typically accompany them, it would appear. In fact, those in the highest quartile of DHA/EPA intake had a (non-significant) 11% increase in risk of heart attack. But when they statistically factored out the PCBs, DHA/EPA was (weakly and non-significantly) associated with a 26% reduction in heart attack risk. The relevant data is summarized in this table with my highlights, for anyone who wants to see the details: To summarize, it looks like if you can get DHA/EPA without the accompanying PCBs, it may be a slight win for heart attack risk. But when the DHA/EPA comes as a package deal with PCBs (would you like fries with that?), as it did for these fish-eating Swedish women, it's bad news. And its looks it might be even worse for us skinny folks, since they found: In a stratified analysis, we observed a higher RR [of high dietary PCBs] (2.39; 95% CI, 1.15–4.96) among lean women (waist circumference b80 cm) than among those with abdominal adiposity, however the interaction was not statistically significant (p value = 0.18) and the confidence interval was wide. ... Our results indicate a stronger association between PCB and risk of myocardial infarction among lean women meanwhile no association among women with abdominal adiposity. One likely explanation behind the observation is the higher concentrations of circulating PCBs in blood and lower dilution of PCBs in adipose tissue of lean than of obese woman [22]. Fortunately, it is possible to ensure one gets DHA/EPA without the PCBs, by choosing an algae source of DHA/EPA, like this one, rather than taking one's chances eating fish what one hopes is low in contaminants like PCBs, but which can often be mislabelled. --Dean ------------ [1] Int J Cardiol. 2015 Mar 15;183:242-8. doi: 10.1016/j.ijcard.2015.01.055. Epub 2015 Jan 27. Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction - a population-based prospective cohort study. Bergkvist C(1), Berglund M(2), Glynn A(3), Wolk A(1), Åkesson A(4). Sci-hub.io full text: http://www.sciencedirect.com.sci-hub.io/science/article/pii/S0167527315000820 BACKGROUND: Fish consumption may promote cardiovascular health. The role of major food contaminants, such as polychlorinated biphenyls (PCBs) common in fatty fish, is unclear. We assessed the association between dietary PCB exposure and risk of myocardial infarction taking into account the intake of long-chain omega-3 fish fatty acids. METHODS: In the prospective population-based Swedish Mammography Cohort, 33,446 middle-aged and elderly women, free from cardiovascular disease, cancer and diabetes at baseline (1997) were followed-up for 12 years. Validated estimates of dietary PCB exposure and intake of fish fatty acids (eicosapentaenoic acid and docosahexaenoic acid; EPA-DHA) were obtained via a food frequency questionnaire at baseline. RESULTS: During follow-up 1386 incident cases of myocardial infarction were ascertained through register-linkage. Women in the highest quartile of dietary PCB exposure (median 286 ng/day) had a multivariable-adjusted RR of myocardial infarction of 1.21 (95% confidence interval [CI], 1.01-1.45) compared to the lowest quartile (median 101 ng/day) before, and 1.58 (95% CI, 1.10-2.25) after adjusting for EPA-DHA. Stratification by low and high EPA-DHA intake, resulted in RRs 2.20 (95% CI, 1.18-4.12) and 1.73 (95% CI, 0.81-3.69), respectively comparing highest PCB tertile with lowest. The intake of dietary EPA-DHA was inversely associated with risk of myocardial infarction after but not before adjusting for dietary PCB. CONCLUSION: Exposure to PCBs was associated with increased risk of myocardial infarction, while some beneficial effect was associated with increasing EPA and DHA intake. To increase the net benefits of fish consumption, PCB contamination should be reduced to a minimum. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. PMID: 25679993 ------------ [2] EFSA Journal 2010; 8(7):1701. [35 pp.]. doi:10.2903/j.efsa.2010.1701. European Food Safety Authority; Results of the monitoring of non dioxin-like PCBs in food and feed. Free Full text: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/1701.pdf ABSTRACT Non dioxin-like polychlorinated biphenyls (NDL-PCBs) are persistent organic chemicals that accumulate in the environment and humans and are associated with a broad spectrum of health effects. Processing and distribution of PCBs has been prohibited in almost all industrial countries since the late 1980s but they still can be released into the environment from electrical appliances, building paint and sealants and waste sites that contain PCBs. In 2002 the European Commission prescribed a list of actions to be taken to reduce the presence of dioxins and PCBs in food and feed and Member States were recommended to monitor the situation. A total of 12,563 food and feed samples collected in the period 1995 - 2008 from 18 EU Member States, Iceland and Norway were retained for a detailed analysis of the occurrence of the six indicator NDL-PCBs (# 28, 52, 101, 138, 153, and 180). Overall, 18.8% of the results for single congeners were below the limit of quantification (LOQ) but their distribution varied highly between food and feed groups. PCB-153 and PCB-138 were the most commonly detected congeners. In food, the highest mean contamination level was observed in fish and fish derived products followed by eggs, milk and their products, and meat and meat products from terrestrial animals. The lowest contamination was observed in foods of plant origin. A similar pattern was observed in feed where high contamination was reported in feed containing fish derived products and comparatively very low levels in feed of plant or mineral origin. The sum of the six NDL-PCBs was on average close to five times higher than the sum of the 12 dioxin-like PCBs. This relationship varied across food groups and is presumably related to the origin of samples and the contamination source. Country-specific clustering has been observed in several food and feed groups.
  16. All, As discussed in this thread, evidence suggests ALA may be beneficial for brain health in most people, while DHA/EPA may be a mixed blessing - only helpful for avoid Alzheimer's disease (but not other forms of dementia) in those with the APOE4 allele. And as discussed in this thread, fatty fish high in DHA/EPA may be detrimental for cardiovascular health if contaminated with PCBs, as was the case in several studies of Swedish fish eaters. But this new study [1] shared by Al Pater (thanks Al!) found in another population of fish eaters, this time from Spain, dietary DHA/EPA may in fact be beneficial for avoiding cardiovascular mortality. But dietary DHA/EPA was not significantly beneficial for all-cause mortality. For dietary Alpha Linolenic Acid (ALA) which is an omega-3 from plants (e.g. walnuts, olive oil, flax, chia seeds) the opposite was the case. Namely, dietary ALA reduced all-cause mortality, but not cardiovascular mortality risk. Putting the two together, people who met the dietary recommendations for both DHA/EPA and ALA had the lowest all-cause mortality risk - 37% lower than those who didn't meet either recommendation. Perhaps the fish from Spain have less PCBs than Swedish fish (no - I don't mean the candy :-) ). The full text of the study did not address DHA/EPA supplements - DHA/EPA intake was assessed solely from dietary sources. So it is not clear if a similar beneficial effect could be achieved through a combination of ALA from plant sources and DHA/EPA supplements as fish oil or algae oil, both of which are less likely to be contaminated with mercury or PCBs than the flesh of whole fish. --Dean ------ [1] J Am Heart Assoc. 2016 Jan 26;5(1). pii: e002543. doi: 10.1161/JAHA.115.002543. Dietary Alpha-Linolenic Acid, Marine Omega-3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study. Sala-Vila A, Guasch-Ferré M, Hu FB, et al. http://jaha.ahajournals.org/content/5/1/e002543.long http://jaha.ahajournals.org/content/5/1/e002543.full.pdf+html Abstract BACKGROUND: Epidemiological evidence suggests a cardioprotective role of Alpha-linolenic acid (ALA), a plant-derived Omega-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine Omega-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long-chain n-3 polyunsaturated fatty acids (=/>500 mg/day). METHODS AND RESULTS: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-cause mortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-cause mortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). CONCLUSIONS: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids. KEYWORDS: fatty acid; nutrition; sudden cardiac death PMID: 26813890
  17. Your mom didn't know how right she was when she told you to eat your fruits & vegetables (F/V), at least if you are a girl... This new study [1] in the journal Circulation assessed the diets of 2500 young black and white men and women (~25 years of age, 62% female) and then measured their level of artery calcification 20 years later using computed tomography - arguably the 'gold standard' for assessing artery health. It found that people eating the most F/V (highest tertile - 7-9 servings / day) were 25% less likely 20 years later to have developed calcified arteries relative to the lowest F/V eaters (2-4 servings / day). From the full text, here are a few of the highlights, including one kicker: Fruits and vegetables were about equally protective Including legumes in with the vegetable category kept the association about the same - i.e. legumes were about as good for arteries as fruits & veggies. Of course people eating lots of F/V had healthier diets in other ways as well, but the inverse association between F/V and artery calcification was still significant even after controlling for these other dietary factors. Shockingly left out of the abstract was the fact that the inverse relationship between F/V intake and artery calcification (CAC) was only observed in women! To quote the full text: [R]eported intake of F/V did not appear to be associated with prevalent CAC among men: OR (95% CI) 1.0 (ref), 0.77 (0.52-1.12), 0.89 (0.60-1.31), p-value for trend 0.67 Here was their explanation for this surprising results: The lack of association between F/V intake and CAC in men in our study may be due to a lack of power, as our study included only 935 male participants. However, a less significant association between CVD and F/V intake in men has been seen in other studies. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heart study demonstrated a 15% (95% CI: 6% to 23%) lower risk for CHD mortality per 80gram/day increase in fruit and vegetable intake in women, but a non-significant 2% (95% CI: -2% to +2%) CHD mortality reduction in men (p-value for heterogeneity 0.007) [2] Similar findings were reported in a cohort of Japanese women and men.3 In the CHD risk factor study INTERHEART, the 3 lifestyle behaviors associated with a lower risk of CHD were F/V intake, exercise, and moderate alcohol consumption, and the protective effects of exercise and moderate alcohol consumption were larger in women compared to men with a trend towards F/V intake being more protective in women as well.[3] So why did the researchers leave out this surprising lack of inverse relationship between F/V intake and later artery calcification in men from both the abstract and from the popular press coverage of this study? Perhaps so as to avoid undermining the credibility of their (laudable) public health message, as summarized in the concluding sentence of the abstract: Our results reinforce the importance of establishing a high intake of F/V as part of a healthy dietary pattern early in life. Somehow I was unaware of the attenuated CVD benefits men seem to get from eating lots fruits and vegetables. --Dean ---------- [1] Circulation. 2015 Oct 26. pii: CIRCULATIONAHA.114.012562. [Epub ahead of print] The Association of Fruit and Vegetable Consumption During Early Adulthood With the Prevalence of Coronary Artery Calcium After 20 Years of Follow-Up: The CARDIA Study. Miedema MD(1), Petrone A(2), Shikany JM(3), Greenland P(4), Lewis CE(3), Pletcher MJ(5), Gaziano JM(2), Djousse L(2). Free full text: http://circ.ahajournals.org/content/early/2015/10/14/CIRCULATIONAHA.114.012562.long BACKGROUND: -The relationship between intake of fruits and vegetables (F/V) during young adulthood and coronary atherosclerosis later in life is unclear. METHODS AND RESULTS: -We studied participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of young, healthy black and white individuals at baseline (1985-1986). Intake of F/V at baseline was assessed using a semi-quantitative interview administered diet history and CAC was measured at year 20 (2005-2006) using computed tomography. We used logistic regression to adjust for relevant variables and estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) across energy-adjusted, sex-specific tertiles of total servings of F/V per day. Among our sample (n=2,506), the mean (SD) age at baseline was 25.3 (3.5) years and 62.7% were female. After adjustment for demographics and lifestyle variables, higher intake of F/V was associated with a lower prevalence of CAC: OR (95% CI) =1.00 (reference), 0.78 (0.59-1.02), and 0.74 (0.56-0.99), from the lowest to the highest tertile of F/V, p-value for trend <0.001. There was attenuation of the association between F/V and CAC after adjustment for other dietary variables but the trend remained significant: OR (95% CI): 1.00 (reference), 0.84 (0.63-1.11), and 0.92 (0.67-1.26), p-value for trend <0.002]. CONCLUSIONS: -In this longitudinal cohort study, higher intake of F/V during young adulthood was associated with lower odds of prevalent CAC after 20 years of follow-up. Our results reinforce the importance of establishing a high intake of F/V as part of a healthy dietary pattern early in life. PMID: 26503880 ------------ [2] Eur Heart J. 2011;32:1235–1243. Fruit and vegetable intake and mortality from ischaemic heart disease: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heart study. Crowe FL, Roddam AW, Key TJ, Appleby PN, Overvad K, Jakobsen MU, Tjønneland A, Hansen L, Boeing H, Weikert C, Linseisen J, Kaaks R, Trichopoulou A, Misirli G, Lagiou P, Sacerdote C, Pala V, Palli D, Tumino R, Panico S, Bueno-de-Mesquita HB, Boer J, van Gils CH, Beulens JW, Barricarte A, Rodríguez L, Larrañaga N, Sánchez MJ, Tormo MJ, Buckland G, Lund E, Hedblad B, Melander O, Jansson JH, Wennberg P, Wareham NJ, Slimani N, Romieu I, Jenab M, Danesh J, Gallo V, Norat T, Riboli E; ------------ [3] Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): casecontrol study. Lancet. 2004;364:937–952.
  18. Dean Pomerleau

    Total Cholesterol and Heart Attacks

    [Another one for the "non-CR diet and health" forum. If such a forum ever gets created, I promise I'll use my moderator super-powers to move all these threads to the new forum!] Dr. Greger's latest video titled Everything in Moderation? Even Heart Disease? has this interesting graph from [1] of cardiovascular disease and heart attacks as a function of total serum cholesterol level (click to enlarge): It shows that 35 percent of heart attacks occur in people with total serum cholesterol between 150 and 200 mg/dL. I had no idea it was that high. And virtually no heart attacks occur in people with cholesterol below 150 mg/dL, which is why many people (including me) have said it makes you virtually "heart attack proof". But then I started thinking, wait a minute. Couldn't this simply be a reflection of population statistics, and not reflect a causal relationship between cholesterol level and heart attacks? To understand this possibility, consider a similar plot of height vs. # of heart attacks. Assuming heart attacks are totally independent of height, you'd still see a similar bell curve of the number of heart attacks plotted against height, for the simple reason that height is distributed along a bell curve. So 50% of heart attacks would occur in men below the median height of 5'10" in the US, and furthermore only a tiny fraction of heart attacks (~3%) would occur in men shorter than 5'2", which is two standard deviations below the median. Does that mean that having a very short stature makes you heart attack proof? Of course not, it just means that there aren't many men shorter than 5'2" to contribute to the heart attack statistics. As an admirer of both Dr. Greger's work, I am sometimes disappointed when he uses potentially misleading statistics like this one to advance his perspective on diet and health (i.e. the value of following a plant-based diet - which I very much agree with). So what is the more accurate picture of the relationship between cholesterol and heart attack risk? Here is a graph, from [2], which BTW has a very good overview of various blood markers, including cholesterol sub-components and their association with CHD: As you can see from the graph on the right, CHD mortality rate (as opposed to total # of heart attacks) appears to be pretty asymptotic below 200 mg/dL. It's only when you get up to a total cholesterol of about 225 mg/dL that you see CHD mortality rate rising significantly, above which it goes through the roof. This is what's called evidence-based medicine, and it is why the American Heart Association and European equivalent (the European Societies for Cardiology, Hypertension and Diabetes) recommend keeping total cholesterol below 190-200, rather than necessarily trying to push it below 150 using diet or statins. With the latter, you might end up like this guy : So despite what Dr. Greger suggests, keeping one's total cholesterol below 150 mg/dL, as opposed to somewhere in the range of 150-200 mg/dL, doesn't appear to provide a dramatic benefit in terms of heart attack risk. To be fair, Dr. Greger has another video on the optimal cholesterol level for heart health that does seem to get the science better. It ignores total cholesterol level, and instead looks at all the randomized control trials of cholesterol lowering drugs, which suggest that an LDL level below 70 mg/dL (about 1/2 the average LDL level in US adults, 130 mg/dL) does make one virtually "heart attack proof". But then again, the relevance of results from people who are taking statins, not to mention the relevance for us of statin-induced LDL reduction or other positive effects of statins, make it far from certain that these results apply to people keeping LDL cholesterol low through diet and lifestyle choices. --Dean --------------- [1] Atherosclerosis. 1996 Jul;124 Suppl:S1-9. Lipids, risk factors and ischaemic heart disease. Castelli WP(1). Author information: (1)Framingham Cardiovascular Institute, MA 01701-9167, USA. Over 200 risk factors for cardiovascular disease (CVD) have now been identified. Among these, the three most important are (1) abnormal lipids, including the fact that there are more than 15 types of cholesterol-containing lipoproteins and four different types of triglyceride-rich particles, some of which are very atherogenic, (2) high blood pressure, and (3) cigarette smoking. In addition, many other factors including diabetes, haemostatic factors such as fibrinogen, factor VII, plasminogen activator inhibitors, and new factors such as apolipoprotein E4 and homocysteine, are known to increase the risk of developing clinical CVD. A low risk for CVD requires that these various factors are present in the circulation in the correct proportions. Two simple tests for determining plasma lipid levels can be used to identify those individuals with an atherogenic lipid profile and who are, therefore, at increased risk for CVD. Firstly, the ratio of total cholesterol to high density cholesterol (HDL cholesterol) should be determined, followed by measurement of plasma triglyceride concentrations. This will allow differentiation of whether the low density lipoproteins (LDL), HDL cholesterol or triglyceride-rich particles such as the small dense beta-very low density lipoproteins (VLDL) are the major cause for concern. Once identified, those individuals with a high lipid risk profile should be treated before, rather than after, experiencing coronary heart disease (CHD). PMID: 8831910 ------------------- [2] The Journal of the International Federation of Clinical Chemistry and Laboratory Medicine Vol 13:2 (2003) THE ROLE OF LIPIDS IN THE DEVELOPMENT OF ATHEROSCLEROSIS AND CORONARY HEART DISEASE: GUIDELINES FOR DIAGNOSIS AND TREATMENT Victor Blaton Department of Clinical Chemistry, Hospital AZ Sint-Jan AV, Brugge, Belgium pdf: http://www.ifcc.org/ifccfiles/docs/140206200306.pdf
  19. [Another one for the "Non-CR Health forum"...] Recently there has been much hype in the popular press, including a Time Magazine story, with this provocative cover: that claim we've been wrong about saturated fat (like butter) all along. These stories have been based on meta-analyses like this one [1], that purport to find no association between saturated fat and chronic diseases, even cardiovascular disease. One of my favorite nutrition bloggers, PlantPositive, did a thorough debunking of the Time story and the people & studies it uses as sources. Among other faults of these previous meta-analyses outlined in PlantPositive's post, some of the biggest problems include: Over correction by factoring out serum cholesterol in the analysis - which is elevated by saturate fat intake and so shouldn't be controlled for. Failing to factor out the low cholesterol of saturated fat eaters who take statins to control their cholesterol. Failing to account for the health effects of what people choose to eat instead when they don't eat saturated fat-rich foods. As I recall (but an unable to verify due to the archives being down... ), we talked about all these studies and their shortcomings on the CR email list before. But now, we have something even better than critical analysis of flawed studies. We have a new prospective cohort study [2] of some of the best data available on diet, lifestyle and health from the Health Professionals and Nurses Health Studies. It appears to do a much better job, particularly with respect to the third confounder - food substitution effects. Here is popular press coverage of the new study. The Harvard researchers have followed these two cohorts of 42K men and 84K women for over 30 years, assessing their diet, lifestyle and health repeatedly during that time. This study looked at their fat consumption habits, and in particular changes in those habits over time and how those changes relate to coronary heart disease (CHD). In a nutshell, they found that: Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10). Here is a graphical depiction of these results: As you can see, trans fat is toxic relative to any other foods, including saturate fat - no surprise. More interestingly, it is about a wash to substitute saturated fat with refined carbohydrates when it comes to heart disease risk. But substituting any of the following for saturated fat results in significantly reduced CHD risk - MUFA, PUFA and whole grain carbohydrates. PUFAs appear particularly protective. Unfortunately the study did not address other healthy carbohydrate sources besides whole grains, like fruits, vegetables or legumes (which I willing to bet would do at least as well as whole grains at reducing CHD risk relative to saturated fat). They also didn't discriminate between the health effects of different types of saturated fats, some of which might not be as bad as others (i.e. those found in plants vs. animal sources). One concern is that when people clean up their diet by eliminating saturated fat, they might also undertake other health promoting lifestyle changes, making it appear that reducing saturated fat was beneficial when it actually was the other changes that made the difference. The authors addressed this potential problem by controlling for a host of other factors in their analysis, including: The multivariable model was adjusted for total energy intake, the energy contribution from protein, cholesterol intake, alcohol intake, smoking status, body mass index, physical activity, use of vitamins and aspirin, family history of myocardial infarction and diabetes, and presence of baseline hypercholesterolemia and hypertension. These results confirm what I think most people have believed all along - that saturated fat is detrimental to heart health, but probably no more so than what people will normally eat instead, crappy carbs. This explains those previous studies that found lower saturated fat intake was often not associated with lower risk of heart disease - people who ate less saturated fat were eating more refined carbs instead, and so weren't any better off. But when you replace saturated fat-rich foods with healthy fats or healthy carbs, you reduce your risk of heart disease dramatically. --Dean --------------- [1] BMJ. 2015 Aug 11;351:h3978. doi: 10.1136/bmj.h3978. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. de Souza RJ(1), Mente A(2), Maroleanu A(3), Cozma AI(4), Ha V(5), Kishibe T(6), Uleryk E(7), Budylowski P(8), Schünemann H(9), Beyene J(10), Anand SS(11). OBJECTIVE: To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled. Heterogeneity was assessed and quantified. Potential publication bias was assessed and subgroup analyses were undertaken. The GRADE approach was used to evaluate quality of evidence and certainty of conclusions. RESULTS: For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90 501-339 090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12 942-230 135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27). Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18 (1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73 to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated fat and all outcomes was "very low." The certainty of associations of trans fat with CHD outcomes was "moderate" and "very low" to "low" for other associations. CONCLUSIONS: Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats. © de Souza et al 2015. PMCID: PMC4532752 PMID: 26268692 ------------ [2] J Am Coll Cardiol. 2015 Oct 6;66(14):1538-48. doi: 10.1016/j.jacc.2015.07.055. Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study. Li Y(1), Hruby A(1), Bernstein AM(2), Ley SH(1), Wang DD(1), Chiuve SE(3), Sampson L(1), Rexrode KM(4), Rimm EB(5), Willett WC(5), Hu FB(6). BACKGROUND: The associations between dietary saturated fats and the risk of coronary heart disease (CHD) remain controversial, but few studies have compared saturated with unsaturated fats and sources of carbohydrates in relation to CHD risk. OBJECTIVES: This study sought to investigate associations of saturated fats compared with unsaturated fats and different sources of carbohydrates in relation to CHD risk. METHODS: We followed 84,628 women (Nurses' Health Study, 1980 to 2010), and 42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years. RESULTS: During 24 to 30 years of follow-up, we documented 7,667 incident cases of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates from whole grains were significantly associated with a lower risk of CHD comparing the highest with lowest quintile for PUFAs (hazard ratio : 0.80, 95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend = 0.003). In contrast, carbohydrates from refined starches/added sugars were positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p trend = 0.04). Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10). CONCLUSIONS: Our findings indicate that unsaturated fats, especially PUFAs, and/or high-quality carbohydrates can be used to replace saturated fats to reduce CHD risk. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. PMCID: PMC4593072 [Available on 2016-10-06] PMID: 26429077
  20. In my exploration of nutrigenomics, I came across this interesting recent study [1] that looked at the interaction between a particular gene polymorphism (rs4977574 - available on 23andMe) and cardiovascular disease (CVD), as mediated by consumption of either vegetables or wine. The researchers followed 24,000 people for 15 years, during which time about 3000 of them developed cardiovascular disease. So it was a pretty big cohort, with lots of people experiencing the outcome in question - cardiovascular disease. Across the entire population, eating more veggies and drinking more wine resulted in less CVD - not too surprising given previous research on the health benefits of these foods. Things got more interesting when the researchers looked at polymorphisms of SNP rs4977574. Having one or two of the risk alleles (G worse than A) for this SNP on chromosome 9 has been previously shown to be associated with an increased risk of CVD [2]. For example, study [3] found for every G allele one carries, one has about a 13% increased risk of CVD. Study [2] was similar - in the 20-25% of the population that carry two G alleles for this SNP, risk of CVD was increased 30-40% relative to people with AA for rs4977574. This new study [1] found something very similar - for each additional G allele at rs4977574, people were 16% more likely to develop CVD. And these polymorphisms are quite common, ~30% of the study population were AA for rs4977574, 50% were AG, and 20% were GG. But things got really interesting when they looked at how vegetable and wine consumption influenced with the link between this polymorphism and CVD. For people with two 'normal' alleles for rs4977574 (AA), increasing vegetable intake was associated with lower CVD, just like in the population as a whole - no surprise. But for people with either one or two G's for rs4977574, higher vegetable intake didn't help! In other words, compared with high consumers of vegetables who carried two A's for rs4977574 (the reference group), people with AG for rs4977574 were 20-30% more likely to develop CVD, and people with GG for rs4977574 were 40-50% more likely to develop CVD, regardless of how many vegetables they ate! The opposite was true for wine. Wine didn't help reduce risk of CVD in AA carriers for rs4977574, but it did reduce risk in AG and GG carriers, by ~30% and ~40% respectively! In fact, drinking wine appeared to nearly entirely counteract the baseline increased risk of CVD in AG and GG carriers, relative to AA carriers. Here is the relevant table of results from the paper for those interested in the precise details: In summary, this study suggests that if you have one or (especially) two G alleles for rs4977574, you are at higher risk for cardiovascular disease, and that consuming wine, but not vegetables, can help lower your risk. FYI, 23andMe shows I've got one G allele for rs4977574 - which is a bummer since I love veggies and don't drink alcohol. :( Of course its only one study, and one gene locus, so the results should be taken with a grain of salt. I don't plan to eat fewer veggies or take up drinking as a result of this study, particularly since alcoholism runs in my family. I figure my good cholesterol numbers and healthy diet/lifestyle make it unlikely I'll die of CVD anyway. But it seems like another interesting example how genes and diet/lifestyle can interact to influence health in significant and sometimes surprising ways. --Dean ------------------------------------------- [1] BMC Med Genet. 2014 Dec 31;15(1):1220. [Epub ahead of print] The chromosome 9p21 variant interacts with vegetable and wine intake to influence the risk of cardiovascular disease: a population based cohort study. Hindy G, Ericson U, Hamrefors V, Drake I, Wirfält E, Melander O, Orho-Melander M. Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331503/pdf/12881_2014_Article_138.pdf AbstractBackgroundChromosome 9p21 variants are associated with cardiovascular disease (CVD) but not with any of its known risk markers. However, recent studies have suggested that the risk associated with 9p21 variation is modified by a prudent dietary pattern and smoking. We tested if the increased risk of CVD by the 9p21 single nucleotide polymorphism rs4977574 is modified by intakes of vegetables, fruits, alcohol, or wine, and if rs4977574 interacts with environmental factors on known CVD risk markers.MethodsMultivariable Cox regression analyses were performed in 23,949 individuals from the population-based prospective Malmö Diet and Cancer Study (MDCS), of whom 3,164 developed CVD during 15 years of follow-up. The rs4977574 variant (major allele: A; minor allele: G) was genotyped using TaqMan® Assay Design probes. Dietary data were collected at baseline using a modified diet history method. Cross-sectional analyses were performed in 4,828 MDCS participants with fasting blood levels of circulating risk factors measured at baseline.ResultsEach rs4977574 G allele was associated with a 16% increased incidence of CVD (95% confidence interval (CI), 1.10¿1.22). Higher vegetable intake (hazard ratio (HR), 0.95 [CI: 0.91¿0.996]), wine intake (HR, 0.91 [CI: 0.86¿0.96]), and total alcohol consumption (HR, 0.92 [CI: 0.86¿0.98]) were associated with lower CVD incidence. The increased CVD incidence by the G allele was restricted to individuals with medium or high vegetable intake (Pinteraction¿=¿0.043), and to non- and low consumers of wine (Pinteraction¿=¿0.029). Although rs4977574 did not associate with any known risk markers, stratification by vegetable intake and smoking suggested an interaction with rs4977574 on glycated hemoglobin and high-density lipoprotein cholesterol (Pinteraction¿=¿0.015 and 0.049, respectively).ConclusionsOur results indicate that rs4977574 interacts with vegetable and wine intake to affect the incidence of CVD, and suggest that an interaction may exist between environmental risk factors and rs4977574 on known risk markers of CVD. PMID: 25551366 --------------------- [2] Science. 2007 Jun 8;316(5830):1488-91. Epub 2007 May 3. A common allele on chromosome 9 associated with coronary heart disease. McPherson R1, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC. Author information AbstractCoronary heart disease (CHD) is a major cause of death in Western countries. We used genome-wide association scanning to identify a 58-kilobase interval on chromosome 9p21 that was consistently associated with CHD in six independent samples (more than 23,000 participants) from four Caucasian populations. This interval, which is located near the CDKN2A and CDKN2B genes, contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension, or diabetes. Homozygotes for the risk allele make up 20 to 25% of Caucasians and have a approximately 30 to 40% increased risk of CHD. PMID: 17478681 --------------------------------- [3] J Intern Med. 2013 Sep;274(3):233-40. doi: 10.1111/joim.12063. Epub 2013 Mar 25. Chromosome 9p21 genetic variation explains 13% of cardiovascular disease incidence but does not improve risk prediction. Gränsbo K1, Almgren P, Sjögren M, Smith JG, Engström G, Hedblad B, Melander O. Author information AbstractOBJECTIVES:To evaluate the proportion of cardiovascular disease (CVD) incidence that is explained by genetic variation at chromosome 9p21 and to test whether such variation adds incremental information with regard to CVD prediction, beyond traditional risk factors. DESIGN, SETTING AND PARTICIPANTS:rs4977574 on chromosome 9p21 was genotyped in 24 777 subjects from the Malmö Diet and Cancer study who were free from CVD prior to the baseline examination. Association between genotype and incident CVD (n = 2668) during a median follow-up of 11.7 years was evaluated in multivariate Cox proportional hazard models. Analyses were performed in quartiles of baseline age, and linear trends in effect size across age groups were estimated in logistic regression models. RESULTS:In additive models, chromosome 9p21 significantly predicted CVD in the entire population (hazard ratio 1.17 per G allele, 95% confidence interval 1.11-1.23, P < 0.001). Effect estimates increased from the highest (Q4) to the lowest quartile (Q1) of baseline age, but this trend was not significant. The overall population attributable risk conferred by chromosome 9p21 in fully adjusted models was 13%, ranging from 17% in Q1 to 11% in Q4. Addition of chromosome 9p21 to traditional risk factors only marginally improved predictive accuracy. CONCLUSION:The high population attributable risk conferred by chromosome 9p21 suggests that future interventions interfering with downstream mechanisms of the genetic variation may affect CVD incidence over a broad range of ages. However, variation of chromosome 9p21 alone does not add clinically meaningful information in terms of CVD prediction beyond traditional risk factors at any age.
  21. All: https://healthyheartscore.sph.harvard.edu No bloodwork -- just lifestyle factors. Designed around this study: A story about this from NPR: http://www.npr.org/blogs/health/2014/11/14/364086181/more-squash-less-bacon-calculating-your-real-life-heart-risk Interestingly, it flagged my BMI as a significant risk, but still gave me an overall "ideal" risk score. Reference 1: Chiuve SE, Cook NR, Shay CM, Rexrode KM, Albert CM, Manson JE, Willett WC, Rimm EB. Lifestyle-Based Prediction Model for the Prevention of CVD: The Healthy Heart Score. J Am Heart Assoc. 2014 Nov 14;3(6). pii: e000954. PubMed PMID: 25398889. http://jaha.ahajournals.org/content/3/6/e000954.full
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