Drugs that tamp down inflammation in the brain could slow cognitive decline

Very few vegetables (starchy tubers are the main exception) contain much sugars (and specifically fructose, which is uniquely bad for your liver), so I think it's worth separating out fruit vs vegetables, but yes, there's also a very different metabolic response to acellular sugars (the best review I've seen on the subject is actually a talk given by Gabor Erdosi: https://www.youtube.com/watch?v=8rcfvRGZsDs), but I'd also say that the harm is contextual. If you're metabolically flexible, or if you're actively replenishing muscle or liver glycogen, your body comp is where you want it, and your insulin sensitivity/glucose disposal is good, then yeah, sure, have some fruit if you want. If you're like the majority of American adults though, then it's probably not doing you any favors.

* 2013–2014 NHANES Data shows 70.2% of US adults are overweight or obese. [1] 37.7% being obese. Note, that this percentage is reported at 39.8% in 2015-2016 (using the same NHANES data). [2]

* The NIH estimates that "Between 30 and 40 percent of adults in the United States have NAFLD." [3]

* The CDC says: "An estimated 33.9% of U.S. adults ... had prediabetes in 2015" and "Nearly half (48.3%) of adults aged 65 years or older had prediabetes." (only 1/3 are "aware" of this). Another 9.4% of the population is estimated to be diabetic. [4] That means well over half of American adults are pre-diabetic or diabetic, and that number is only going up.

It's important to recognize that diabetes is only the endpoint and it is usually preceded with Metabolic Syndrome markers. Here's a recent analysis of 2009-2016 NHANES data: https://www.liebertpub.com/doi/10.1089/met.2018.0105

* 80.1% of Americans had at least one marker of MetS by ATP III criteria

* Using more restrictive (calculated in the study) cutoffs gave a result of 12.2% of American adults in "optimal metabolic health"

Sadly, what's notably missing from all of this is measurement of fasting insulin - almost no one gets this measured (and I've both had personal experience and tons of stories from friends where Doctor's will actively fight back when requesting to have your FI tested) - it's been know for decades that hyperinsulemia and insulin resistance (best calculated by HOMA or HOMA2, indices which require FG and FI to calculate) will precede hyperglycemia by years or decades (subclinical diabetes). The insulin assay costs $8 direct-to-consumer pricing in the US when added onto standard FG/A1c testing. (FI is also required to calculate your NAFLD LFS, the best index for diagnosing NAFLD.)

To me, what was sort of shocking/amazing to me after doing my own research is how negligently ignorant GPs/clinicians are about literally the most common disease that's killing their patients.

Based on what I've learned this year, I have some (pretty well-founded IMO) opinions now, but I'm actually not all that interested in these Nutrition Wars arguments (the quality of the research is very poor and population-level dietary policy has honestly been such a disaster, but almost impossible to turn around due to institutional momentum/regulatory capture) but so much of metabolic health is contextual and bio-individual. I'd rather people pick some good surrogate markers they can track sequentially and then make controlled lifestyle modifications and see what actually helps them. Everyone should just do more of what works for them, and do less of what doesn't and worry less about what "experts" say on the matter.

[1] https://www.niddk.nih.gov/health-information/health-statisti...

[2] https://www.cdc.gov/nchs/data/databriefs/db288.pdf

[3] https://www.niddk.nih.gov/health-information/liver-disease/n...

[4] https://www.cdc.gov/diabetes/data/statistics-report/prevalen...

As mentioned, plenty (maybe even most!) vegetables are not very high in digestible carbs - certainly not the ones that are high in fiber and nutrients (you can probably skip the potatoes unless you're on a mono-diet). But this is where I think you really need to reconsider where you're getting you're data from...

> High intake of saturated fat is associated with heart disease.

First off, associations, especially in nutritional epidemiology, is trash:

Ioannidis, John P. A. “The Challenge of Reforming Nutritional Epidemiologic Research.” JAMA, August 23, 2018. https://doi.org/10.1001/jama.2018.11025.

Archer, Edward, Carl J. Lavie, and James O. Hill. “The Failure to Measure Dietary Intake Engendered a Fictional Discourse on Diet-Disease Relations.” Frontiers in Nutrition 5 (November 13, 2018). https://doi.org/10.3389/fnut.2018.00105.

Archer, Edward, Michael L. Marlow, and Carl J. Lavie. “Controversy and Debate: Memory-Based Methods Paper 1: The Fatal Flaws of Food Frequency Questionnaires and Other Memory-Based Dietary Assessment Methods.” Journal of Clinical Epidemiology 104 (December 2018): 113–24. https://doi.org/10.1016/j.jclinepi.2018.08.003.

I don't think people realize just how bad the quality of data is in these sort of survey studies. IMO anything w/ an HR/OR of But more interestingly, is how nutritional myths can sustain after it's been overturned. It turns out that on meta-analysis (n=347747), again keeping in mind how we should treat observational studies, the HR between eating the highest and lowest saturated fat consumption is... exactly 1.0.

Siri-Tarino, Patty W, Qi Sun, Frank B Hu, and Ronald M Krauss. “Meta-Analysis of Prospective Cohort Studies Evaluating the Association of Saturated Fat with Cardiovascular Disease.” The American Journal of Clinical Nutrition 91, no. 3 (March 1, 2010): 535–46. https://doi.org/10.3945/ajcn.2009.27725.

Lets see what some other teams say. This analysis uses the GRADE approach for evidence analysis:

"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."

Souza, Russell J. de, Andrew Mente, Adriana Maroleanu, Adrian I. Cozma, Vanessa Ha, Teruko Kishibe, Elizabeth Uleryk, et al. “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.” BMJ 351 (August 12, 2015). https://doi.org/10.1136/bmj.h3978.

There have still been plenty of studies so lets focus on adequately controlled RCTs, the highest evidence we might have:

"When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86–1.31), total CHD events (RR = 1.02, CI = 0.84–1.23), CHD mortality (RR = 1.13, CI = 0.91–1.40) and total mortality (RR = 1.07, CI = 0.90–1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65–0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70–1.07), CHD mortality (RR = 0.90, CI = 0.70–1.17) and total mortality (RR = 1.00, CI = 0.90–1.10).

Conclusion

Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations."

Hamley, Steven. “The Effect of Replacing Saturated Fat with Mostly N-6 Polyunsaturated Fat on Coronary Heart Disease: A Meta-Analysis of Randomised Controlled Trials.” Nutrition Journal 16 (May 19, 2017). https://doi.org/10.1186/s12937-017-0254-5.

This isn't the only RCT meta-analysis confirming this. Here's one w/ n=62421 from another team:

"The current available evidence found no significant difference in all-cause mortality or CHD mortality, resulting from the dietary fat interventions. RCT evidence currently available does not support the current dietary fat guidelines. The evidence per se lacks generalisability for population-wide guidelines."

Harcombe, Zoë, Julien S. Baker, James J. DiNicolantonio, Fergal Grace, and Bruce Davies. “Evidence from Randomised Controlled Trials Does Not Support Current Dietary Fat Guidelines: A Systematic Review and Meta-Analysis.” Open Heart 3, no. 2 (August 1, 2016): e000409. https://doi.org/10.1136/openhrt-2016-000409.

So how did this come to be in the first place? Harcombe et al have done a ton of interesting research on this topic, which I'll include for those wanting to dive into the history of the topic (I'm personally a bit bored by the whole lipid heart stuff; turns out that MetS is a 10X greater risk factor, and also if you get a CAC scan every 5 years and keep a 0 score, you're CHD risk is basically nil) :

Harcombe, Zoë, Julien S. Baker, Stephen Mark Cooper, Bruce Davies, Nicholas Sculthorpe, James J. DiNicolantonio, and Fergal Grace. “Evidence from Randomised Controlled Trials Did Not Support the Introduction of Dietary Fat Guidelines in 1977 and 1983: A Systematic Review and Meta-Analysis.” Open Heart 2, no. 1 (January 1, 2015): e000196. https://doi.org/10.1136/openhrt-2014-000196.

Harcombe, Zoë, Julien S. Baker, and Bruce Davies. “Evidence from Prospective Cohort Studies Did Not Support the Introduction of Dietary Fat Guidelines in 1977 and 1983: A Systematic Review.” British Journal of Sports Medicine 51, no. 24 (December 2017): 1737–42. https://doi.org/10.1136/bjsports-2016-096409.

Harcombe, Zoë. “Dietary Fat Guidelines Have No Evidence Base: Where next for Public Health Nutritional Advice?” Br J Sports Med 51, no. 10 (May 1, 2017): 769–74. https://doi.org/10.1136/bjsports-2016-096734.

Harcombe, Zoe. “US Dietary Guidelines: Is Saturated Fat a Nutrient of Concern?” British Journal of Sports Medicine 53, no. 22 (November 1, 2019): 1393–96. https://doi.org/10.1136/bjsports-2018-099420.

Oh, just in case anyone wants to dive into the best risk factors I found (and I've done a lot of digging on risk factors) for avoiding heart disease:

Reverse prediabetes (HR: 0.44):

Vistisen, Dorte, Mika Kivimäki, Leigh Perreault, Adam Hulman, Daniel R. Witte, Eric J. Brunner, Adam Tabák, Marit E. Jørgensen, and Kristine Færch. “Reversion from Prediabetes to Normoglycaemia and Risk of Cardiovascular Disease and Mortality: The Whitehall II Cohort Study.” Diabetologia, May 23, 2019. https://doi.org/10.1007/s00125-019-4895-0.

Maintain a CAC=0 (HR: 0.41):

Blaha Michael J., Cainzos-Achirica Miguel, Greenland Philip, McEvoy John W., Blankstein Ron, Budoff Matthew J., Dardari Zeina, et al. “Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease.” Circulation 133, no. 9 (March 1, 2016): 849–58. https://doi.org/10.1161/CIRCULATIONAHA.115.018524.

And a few interesting final thoughts on etiology (and circling back to the original topic of inflammation):

Malhotra, Aseem, Rita F. Redberg, and Pascal Meier. “Saturated Fat Does Not Clog the Arteries: Coronary Heart Disease Is a Chronic Inflammatory Condition, the Risk of Which Can Be Effectively Reduced from Healthy Lifestyle Interventions.” Br J Sports Med 51, no. 15 (August 1, 2017): 1111–12. https://doi.org/10.1136/bjsports-2016-097285.

Tsoupras, Alexandros, Ronan Lordan, and Ioannis Zabetakis. “Inflammation, Not Cholesterol, Is a Cause of Chronic Disease.” Nutrients 10, no. 5 (May 12, 2018). https://doi.org/10.3390/nu10050604.

(Cholesterol is a whole different can of worms than saturated fat (I'll leave that as an exercise to the reader), but cholesterol is also a terrible marker. "Most major heart attacks occur in people with normal cholesterol": https://www.sciencedaily.com/releases/2017/04/170412105837.h...)

Stress, injury, etc

> associations, especially in nutritional epidemiology, is trash: > I think you really need to reconsider where you're getting you're data from...

I'm going to go with established medical science on this one.

> Most medical, scientific, heart-health, governmental, and professional authorities agree that saturated fat is a significant risk factor for cardiovascular disease, including the World Health Organization,[1] the Food and Nutrition Board of the National Academy of Medicine,[2] the Academy of Nutrition and Dietetics,[3] the Dietitians of Canada,[3] the Association of UK Dietitians,[4] the American Heart Association,[5] the British Heart Foundation,[6] the Heart and Stroke Foundation of Canada,[7] the World Heart Federation,[8] the British National Health Service,[9] the United States Food and Drug Administration,[10] and the European Food Safety Authority.[11] All of these organizations recommend restricting consumption of saturated fats to reduce that risk.

https://en.wikipedia.org/wiki/Saturated_fat_and_cardiovascul...

A pleasure!