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Outlive is a book by Stanford and John Hopkins graduate Dr. Attia. I suspect it is also ghost written to a large degree based on the introduction. While the book is quite thick, the reading is engaging and not overly technical. Authors present the idea of using health span rather than life span as a measure for wellness success. They adequately point out the limitations of current medical system and even studies being very short sighted in terms of 1 to 5 years. They bring up the term evidence informed rather than evidence-based as we typically require of medical studies. For his data, Centurion data, animal models, human studies of the most common chronic disease, molecular studies related to aging, and epidemiology are the sources of evidence for more long-term interpretations of ways to live a healthy long life.

Genetically, he mentions ApoE variants related to dementia and FOXO3 related to longevity. The useful point with the latter is that slight nutrient deficiency and exercise seems to activate FOXO3.


Related to nutrient or calorie deficiency leading to the longer longevity, the mechanism author points to is mTOR. This is the mechanistic target of rapamycin which is the only known compound which extends life in mammals. AMPK inhibits mTOR and stimulates new mitochondria to replace old worn energy plants. When nutrients are scarce Mtor is suppressed and cells going to recycling mode breaking down senescent cells and cleaning house. Unlike the book from Jillian Michaels, author states that the benefits of resveratrol and nicotinamide are not confirmed. Interestingly, the data on resveratrol showed benefit for overweight mice but when NIH tested normal mice longevity was not extended. Regarding rapamycin, the author states that moderate to high doses in a cyclical manner have an immune enhancing rather than immune suppressive effect such as when used for organ transplants. The bolus affect inhibits mTOR C1 responsible for longevity but not the M tor C2 which is more of the immune suppressing effect. Author mentions the difficulty with getting a proactive immune modulator approved for the purpose of delaying aging but also mentions the already approved metformin which is under trials. A degree of age delaying seems reasonable to me at this point based on advanced glycation end products that are associated with aging and may be reduced by metformin. This is something I now looked into further due to the cross over discussion with other references I previously reviewed. Metformin works through somewhat unknown mechanisms but "inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NF?B pathway suppression" per 2016 study J Diabetes Res. Whether inflammation or actual amount of AGEs are reduced in humans is data I will now watch for!

In the next section on food abundance the author recommends, like I do, for an annual DEXA scan for visceral body fat. The author persuasively discusses the power of the liver and maintaining proper glucose control. Specifically he states 5 g of glucose across the entire bloodstream would be considered normal whereas just 7 g would equal diabetes. He describes that for glucose that is in the bloodstream while not being engaged in exercise in which muscle can instantly uptake the sugar, the excess energy from glucose will end up in fat cells as triglycerides. LDL and HDL were explained in much more detail than an average physician level knowledge would provide in my opinion. Rather than Good and Bad cholesterold, the auther points to apoA and apoB with apoB being the concern that carries LDL AND OTHER LIPOPROTEINS that contribute to atherosclerosis. HE points out the final consensus in 2015 that "cholesterol is not a nutrient of concern for overconsumption" and clarifies that it is internally manufactured cholesterol not dietary cholesterol to affects humans (unlike the rabbits in studies). There is an excellent analogy of how vessels get blocked by apoB that moves across endothelium and gets stuck easier than apoA and once stuck, can get oxidized and start to clump into clusters. As the clusters are seen as body as needing cleaned up, immune cells called macrophages eat up the unwanted oxidized LDL but if too much is available, explode into a foam cell and create fatty streaks and plaques in the artery that can be seen even with naked eye. Smooth muscle forms reactive fibrous cap over the plaque. This eventually becomes calcified which we see on Coronary calcium scans. HDL is able to save the macrophage before it explodes and return the cholesterol back to the liver for processing. HDL levels do improve outcomes when HDL is high but meds that increase HDL do NOT seem to improve outcomes. Author points to the function of HDL that matters, a factor we can not currently measure. He does assert measuring apoB is much more relevant than LDL with JAMA 2021 study showing each SD of apoB elevation is 38% increased MI risk. HE next mentions those with normal lab values and seemingly fit proper weight individuals that are found to have significant vessel disease. Lp(a) is a likely culprit and this protein travels with apoB and LDL gathering oxidized LDL on the way to getting stuck in endothelium. There it promotes accelration of arterial plaques. Do not confuse apo(a) with apoA associated with HDL. High Lp(a) does not improve with exercise and diet but does decrease by 30% with PCSK9 inhibitors (Dr Short note this includes Proprotein convertase subtilisin/kexin type 9 inhibitors alirocumab, evolocumab, and inclisiran) and AGGRESSIVE decreasing of apoB (Statins). Aggressive to author means infant levels LDL less than 20!?????????

Similar to other authors, monounsaturated fat in olive oil macadamia nuts and avocados are recommended whereas he states a third of those who go on a ketogenic diet have a reflexive dramatic increase in apoB particles (LDL,VLDL, Lp(a)) thus should not be on this type of diet. Author medication choices are Crestor first (Nexletol for statin intolerant) combined with Zetia to block increased absorbtion of cholesterol when statin is blocking cholesterol synthesis. For Lp(a) targeting, alirocumab (Praluent) and evolocumab (Repatha). 4 grams per day EPA/fish oil to target triglycerides.


Next chapter discusses cancer and new treatments which I find to be less relevant for a prevention strategy. He does mention fasting as effective for cancer patients responding to chemotherapy in randomized trials. This is consistent with my interpretation it cancer cells are metabolically hungry and thus reducing their energy source can allow the immune system to catch up. Author mentions liquid biopsies for multi cancer detection of the blood as well as diffusion weighted imaging MRI which has a high false positive but is much more sensitive for detecting cancerous tumors. I do agree that rather than focus on prevention of cancers, early detection should be major focus due to the variability's involved. However, those who are healthy, eat well, and have low exposure to toxins do logically have lower risk of cancer.

In relationship to neurologic degenerative disease, author points to APO E testing and that a drop rapidly of estrogen in women seems to be a trigger for this genetic risk. Thus, perimenopausal hormone replacement may be more persuasive for those at risk of Alzheimer's.

He mentions a correlation of cerebral blood flow with Alzheimer's being decreased and this decrease as a linear correlation with dementia. The differentiation of vascular versus Alzheimer's dementia is questioned. With studies showing metabolic overlap to risk, insulin resistance may play a causal role in the development and progression of Alzheimer's. Addressing this as well as lowering homocysteine with the vitamin B, optimizing omega-3 fatty acids and exercise all may be beneficial. Exercise is the most beneficial per author.

Much like Jillian Michaels book the author divides health domains into 5 keys. Those include exercise nutrition sleep emotional health and exogenous molecules.

In regards to exercise, author points to the VO2 max as the single marker for longevity. He recites various data with the summary that long-term mortality has no upper limit of benefit in association with aerobic fitness (JAMA).


For fitness needed for good healthspan, author recommends setting a physical task list that addresses multiple aspects of our functional capacity. The list he provided:

Regarding fitness studies, the author brings up 1 study which is consistent with my understanding of fasting. Those with metabolic syndrome when exercising have to rely entirely on glucose whereas professional cyclist would burn primarily fat under the same exercise. Basically, my interpretation is that metabolic syndrome has lipid enzymes inactivated because there is always a source of glucose.

Recommended exercise is actually just past walk level but for 4 45 minute sessions per week. Then adding a VO2 max top exertion exercise. For non-aerobic, author focuses on strength not muscle mass. For stability, he recommends eccentric stepping such as 3 seconds.

Regarding dietary studies the author mentions a large NIH study on calorie restriction showed no benefit in monkeys when the calorie restriction diet consisted of 28% sugar but longevity was significantly improved with diminished calories on a 4% sugar diet. The net interpretation is that all calories are not the same and more specifically, I see this as data that sugar intake decreases longevity.

Continuous glucose monitoring is recommended in data derived from CGM includes that not all carbs are created equal. Rice including brown rice is quite glycemic as well as oatmeal but we learned from another book that steel cut oatmeal is not as processed therefore likely is not as glycemic. Exercise well sugar is in the bloodstream is more effective. Cortisol and stress hormones have a surprising impact on blood glucose even if someone is fasting or restricting carbohydrates. Spinach and broccoli and other nonstarch vegetables have virtually no impact on blood sugar. Foods that have high protein and high fat such as eggs or short ribs have virtually no effect on blood sugar assuming no sugar sauce. Recommended protein intake is .75g to 1 g per pound body weight. At 195 pounds, I should have 190 g protein per author.

For sleep, the author points out that cortisol is likely the cause of hide overnight glucose. He also reiterates the information from other books I have are reviewed that sleep deprivation decreases levels of leptin the hormone that tells us we are no longer hungry. Poor sleep is also associated with higher resting heart rate and lower heart rate variability. He mentions the negatives of mostly medicines but does not sometimes prescribe low-dose trazodone or the supplement Ashwanganha. He mentions a drop in body temperature of 1 to 2 degrees helps sleep therefore going from a hot bath to bed is helpful because of the drop in temperature not because of the actual hot water.

The last chapter diverged notably as the author shared his challenges with emotional health. IF interpersonal conflict is a main theme in your life, this section should be read first hand.