The prospective cohort study, named PURE, found that in >135,000 participants from 18 countries, nutritive carbohydrates increase human mortality, whereas dietary fat reduces it, requesting a fundamental change of current nutritional guidelines. Experimental evidence from animal models provides synergizing mechanistic concepts as well as pharmacological options to mimic low-carb or ketogenic diets.
Main Text It has been known since the 1930s that global reduction of food uptake, so-called calorie restriction, extends the lifespan of rodents, other model organisms, including rhesus monkeys, and possibly humans due to an interacting set of experimentally established mechanisms. By contrast and based on observational coincidence rather than prospective causality, dietary recommendations to maintain human health have selectively focused on reduction of nutritive fats, specifically of saturated triglycerides contained within, since the 1970s. An increasing number of prospective studies in large cohorts of humans in the last two decades have repeatedly questioned this practice but have remained widely unnoticed in the general public and also in major parts of the scientific community.
Recently, the findings of the PURE study, consisting of >135,000 individuals recruited from 18 countries of different developmental stages worldwide, has been published (Dehghan et al., 2017). While clinical parameters, socio-economic factors, and detailed food and exercise questionnaires were obtained during initiation of the study, and individuals with pre-existing cardiovascular diseases (but not diabetes) were excluded, after a median follow-up of 7.4 years, together more than 10,000 deaths or events, like myocardial infarction or stroke, had occurred. These were then statistically correlated with the parameters at initiation. Dehghan et al. (2017)) found that carbohydrate intake was associated with increased total mortality. By contrast, any (saturated/monounsaturated/polyunsaturated) type of dietary fat reduced the likelihood of dying. Moreover, there was no link to cardiovascular events or related mortality, except for saturated fats, which were unexpectedly associated with a lower risk of stroke. Consistently, Dehghan et al. (2017)) conclude that “global dietary guidelines should be reconsidered.”
Most dietary carbohydrates relevant for human nutrition contain the monosaccharide D-glucose as a key building block, which, consequently, is transported into the blood to exert release of insulin from the pancreatic ß cells. Glucose is ultimately transported into and metabolized within multiple cell types in a partly insulin-dependent fashion. Impaired insulin and/or insulin-like growth factor 1 (IGF-1) signaling has been shown to extend the lifespan of various model organisms (Friedman and Johnson, 1988 and follow-ups). The glucose-induced release of insulin to activate the corresponding signaling cascade may be considered the key reason as to how increased carbohydrate uptake promotes mortality (Figure 1). Conversely, hyperinsulinemia not only is a hallmark of lifespan-impairing type 2 diabetes, but also specifically promotes malignant growth as reflected by an increased incidence of cancers in diabetics. Notably, while the PURE study could not establish an increase in mortality from cardiovascular causes (see above), the observed increase in global mortality likely is related to the second-frequent cause of death, namely cancers, in states of high-carbohydrate uptake.
From a therapeutic perspective, if carbohydrates are relevant factors in promoting mortality, then not only reduced uptake of these, but also inhibition of carbohydrate uptake or glucose catabolism should extend lifespan. This has been experimentally tested (Figure 1).
(1)The conversion of D-glucose into metabolic intermediates, namely glycolysis, can be inhibited by compounds like (the highly efficient but rather toxic) 2-deoxy-D-glucose or (the less efficient but completely harmless) D-glucosamine (GlcN). The latter is widely used to treat arthrosis with the questionable claim of inducing cartilage regeneration. Both compounds have been shown to extend C. elegans lifespan (Schulz et al., 2007, Weimer et al., 2014), while only GlcN extends lifespan in rodents (Weimer et al., 2014). Notably, GlcN uptake has been also associated with reduced mortality in a large human cohort (Bell et al., 2012). (2)Acarbose is an inhibitor of alpha-glucosidase, an enzyme that releases D-glucose from complex nutritive carbohydrates, most importantly starch, in the intestine. It has been used for the treatment of diabetics to prevent absorption of carbohydrates from the gut since the 1980s. Consistent with the role of carbohydrates in impairing health, acarbose has been shown to extend the lifespan of mice (Harrison et al., 2014). (3)Inhibitors of the renal sodium-glucose co-transporter 2 (SGLT-2) promote removal of D-glucose from the blood via the urine. These rather newly developed inhibitors are being used for the treatment of diabetics. Potential effects on lifespan of model organisms or humans have not been published to date but appear warranted. (4)The antidiabetic compound metformin, which is currently under prospective investigation in regards to lifespan extension (TAME study), exerts its action by reducing glucose production (gluconeogenesis) from the liver, and hence to cause a reduction in circulating blood glucose. Next, a number of studies have evaluated the effects of specific macronutrients on lifespan, initially in S. cerevisiae (Lin et al., 2002), subsequently in C. elegans (Schulz et al., 2007 and follow-ups), and mice. Out of the latter, two studies in the previous issue of Cell Metabolism have studied this in mice starting at 12 months of age. In regards to the PURE study, most notably, the almost complete removal of carbohydrates (<1%) from the diet to generate a ketogenic diet extended lifespan compared to a high-carb diet. However, reconstituting only 10% of energy of the ketogenic diet by sugar abolished this effect (Roberts et al., 2017), suggesting that specifically sugar (rather than carbohydrates in general) has the most relevant effect on lifespan. Along this line, it is also interesting to note that when nutritive sugar content is kept constant, a different (and less extreme) high-carb diet exerts the best effects on murine lifespan. By contrast, a high-fat diet still containing the same amount of sugar, but no other carbs reduced lifespan slightly. Lastly, when combining high-fat and high-carb components from the two previous diets, the worst effect on lifespan was observed (Keipert et al., 2011). Moreover, lifespan extension in mice was also obtained when dietary protein was replaced by carbs, possibly independent of the total uptake in calories (Solon-Biet et al., 2014). Taken together, these studies suggest that dietary sugar may be one important, but not the only, nutritional factor in limiting healthspan in rodents, hence additional studies are definitely required to establish firm evidence in model organisms.
The PURE study has already been criticized for misleadingly generalizing a statistical effect that may be also due to confounding factors. Specifically, income- and geography-dependent nutritional habits of specific subgroups would not be applicable to westernized high-income societies (which, however, had been included into PURE). Indeed, Dehghan et al. (2017)) did not analyze which specific source of carbohydrates (e.g., sugar/refined carbs versus whole-grain products) may contribute to the detrimental effects of carbs observed, especially since income and wealth do impact the quality of dietary choices significantly. This criticism, however, misses the fact that a (not immediately accessible) re-analysis additionally adjusting for household income and wealth, as well as for socioeconomic status of the respective country, did not affect the key observations of the study by any means (appendix, p. 34 of Dehghan et al., 2017).
Taking the body of preceding evidence both from model organisms as well as human epidemiology into account, we therefore believe that current nutritional recommendations in regards to macronutrients, but most importantly in regards to refined carbs and sugar, should indeed be fundamentally reconsidered. Moreover, pharmacological options to mimic low-carb nutrition (i.e., without the need for an actual reduction of carbohydrate intake; Figure 1) may offer a promising approach easier to obtain than achieving changes in nutritional habits of the general population.
Could eating processed foods, such as breakfast and deli meats, be detrimental to your health? Well, according to the World Health Organization (WHO), the answer is yes. Research has shown that eating lunch meat, bacon, or sausage on a daily basis equates to smoking a pack of cigarettes each day and has a similar effect on your health. So, which is actually worse for you, processed meats or smoking? Which causes more deaths worldwide? To find out, let’s delve deeper into the world of junk science. Afterall, deli meats and cigarettes are both labeled Class 1-A carcinogens by the WHO.
Is feeding your child cold cut deli meats now considered “child abuse?”
Surely you wouldn’t put cigarettes on a sandwich and eat it, because then you’d be consuming ammonia, bleach, aluminum, formaldehyde and insecticide. But, if you eat American processed meats, you’ve just consumed all of those carcinogens anyway. Did you just pack a BLT or a ham and cheese sandwich in your child’s school lunch box? If so, you could be doing some serious damage to your their health.
The WHO has made the declaration that eating processed meats regularly is just as dangerous to your health as smoking cigarettes, when it comes to the main causes of cancer. Wonder why? Well for one, the nitrites and nitrates used to preserve meats and protect their color are precursors to N-nitroso compounds (NOCs) that induce tumors in several organs in multiple animal species.
In fact, a study published in the journal Cancer links these preserved cold cut meats to bladder cancer at a 30 percent higher risk for those who consume them. The study used over 300,000 men and women from eight U.S. states over an eight-year period.
What’s worse is that when humans consume sodium nitrite it forms some of the most highly carcinogenic chemical compounds EVER RECORDED in the nutrition world (they’re called nitrosamines). Therefore, feeding your child cold cuts regularly is just as bad as buying them a pack of cigarettes each week and saying, “smoke up!”
And that, my friends, is child abuse.
Top Cancer-Causing Carcinogens: Cigarettes, Alcohol, Asbestos, Arsenic and… wait for it… Bacon, Ham and Sausages
Yes, the UN health body has added a new “terrorist” to the health watch list – cured and processed meats. These group 1 carcinogens lead to bowel cancer, pancreatic cancer and prostate cancer. Who knew? Well, vegetarians and vegans have known for years. It’s not just about farm animal cruelty, but human cruelty too. The IARC (International Agency for Research on Cancer) experts concluded that just one two-ounce portion of processed meat daily increases your chance of getting colon cancer by nearly 20 percent. That’s pretty scary. By the way, that’s only about two SLICES of ham, turkey, chicken, roast beef, salami or bologna, and most people pile them on so thick you can’t even hold the sandwich with one hand.
Just to think everybody, for years, has been avoiding red meat, thinking THAT was the main culprit of disease and disorder, now only to find out it’s basically all cured and processed meats, no matter the color. So much for that red meat myth. Another mainstream lie debunked. Thus, avoiding “red meat” is not a health strategy.
In a statement from the IARC that was published in the journal Lancet Oncology, “We’ve known for some time about the probable link between red and processed meat and bowel cancer, which is backed by substantial evidence.”
Bottom line: Keep your kids off cigarettes, bacon, hot dogs, sausages and deli meat as much as humanly possible. Actual scientific research is proving that the typical American diet of bacon cheeseburgers, ham sandwiches, flu shots and mainstream television turns out to be quite the effective serial killer.
This news is all just another great reason to go vegetarian or vegan and never look back. Plus, if you think you’ll be missing out on some key nutrients, you’re dead wrong. Check out the video below featuring the avid and quite entertaining health researcher Mic the Vegan. It’s good to learn something new every day, and then put it to good use.
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