Following from a sub-thread in the discussion on the New York Academy of Science Conferrence on The Role of Nutrition in Dementia Prevention and Management by two highly intelligent Forum participants:
(The Board software will only let me embed 3 quotes within each other, so what follows all proceeds from Stavia's response to that initial thesis):ApropoE4 wrote:The answers [about ketosis and saturated fat] are in turn: 1. nobody's got a clue. 2. in light of (1), just do what's good for the gen. pop., being more diligent about it.
I would suggest to all concerned that spending decades on a ketogenic diet in the current state of the evidence is a very large — and unwise — bet. If you are trying to prevent AD, you're talking about spending literally a decade or more in a ketogenic state. There is simply no evidence at all on what the long-term health consequences of doing this are: no trials of ketogenic diets have lasted more than a few months (the longer-term low-carb diet trials all intentionally move people off of full-on keto (Atkins "Induction" phase) to a more moderate-carb maintenance approach (Atkins “Ongoing Weight Loss”)), and very few people in the population practice keto diets for any length of time at all, so there is zero prospective epidemiology on long-term outcomes.Stavia wrote:I hear you Apropo, and I agree re large bets. I dont make large bets.ApropoE4 wrote:It's not cynicism, but in the presence of high uncertainty you need to avoid large bets. As far as I know there is no evidence to support a ketogenic diet to prevent, cure, or delay AD. There is some evidence that it helps manage symptoms when the disease is already active. So it's not that there isn't certainty, but there isn't even any indication of probabilityStavia wrote: If the glucose metabolism story is a significant issue for us, then not chasing ketosis as an alternate fuel might have permanent conesquences. [...] Of course there is no certainty, but IMO some yes/no decisons need to be made.
I hear your cynicism ApropoE4, but I dont want to have regrets that I didnt carefully consider options, including long term consequences either way, without bias.
Indeed, the study that keto advocate David Perlmutter disingenuously cites as supporting his recommendations(4) does no such thing, but rather supports a moderately low-carb, Zonish 20: <47 : 37% protein:carb:fat profile (Table 2), with the biggest difference amongst extreme quantiles being low intake of sugar, with which everyone from Ornish to Atkins and the Dietary Guidelines for Americans all endorse. (More dissection of Perlmutter nonsense on the CR Society Listserv, whose Archives are unfortunately down once again just at the moment).
It's possible that at least some Paleo and recent hunter-gatherer populations may have spent much of their lives in a ketogenic state, but we have no data on their risk of age-related dementia: life expectancies were simply too short for AD to have been an outcome that could be sampled (if indeed it could be diagnosed, or evaluated in fossils). (Paleo enthusiasts will say that the life expectancy thing is a red herring, as you have to consider life after censoring out child and infant mortality; even when you do this, life expectancy for recent h-gs has been in the low fifties.(1,2) Similarly, (3) reports that "Up until age 15 or so, hunter-gatherers experience death rates >100-fold higher than in today’s Japan and Sweden, and hunter-gatherer mortality remains >10-fold higher for the entire life span." Plus, Paleo/h-g populations got a hell of a lot of physical activity, which sure seems to be protective against AD and possibly disproportionately so in ApoEε4 carriers, so attributing any findings of low dementia rates, if such data existed, to diet (let alone diet-induced ketosis specifically, rather than low sugar, lots of veggies, etc) would be to pick one data point out of a shotgun scatter).
And even the limited evidence to which ApropoE4 alludes, suggesting that a ketogenic diet may help people with existing AD (not, again, to prevent or delay AD onset) finds that ketogenic diets seem to be ineffective precisely in ApoEε4 carriers:
http://www.neurobiologyofaging.org/arti ... 2/abstract
And remember, one can't make the risk:benefit calculation for keto in a vacuum: one must include the opportunity cost of more evidence-based dietary patterns that seem essentially incompatible. Notably, there is plenty of evidence for the protective effects of the decidedly non-ketogenic Mediterranean diet. Olive oil, most vegetables, fish, wine, and low sugar intake are keto-compatible, but legumes, dairy (other than cheese), fruit, and minimal land-based meat do not.
Similarly, there is substantial evidence that higher saturated fat intake increases one's odds of dementia. It's of course possible to devise a keto diet with low SaFA intake, but it is rather difficult, and certainly incompatible with either use of MCT oil, coconut oil (don't get me started ...), or reliance on standard low-carb cookbooks and blog recipes. (In fact, if you're shooting for 70% fat, even if you had zero fat in your diet except for EVOO, you'd already be at 7% of Calories from SaFA, which the AHA's SaFA limit; if you eat any meat, cheese, coconut oil, etc at all, you'd be over the top).
1: Hillard Kaplan, Kim Hill, Jane Lancaster, and A. Magdalena Hurtado (2000). A Theory of Human Life History Evolution: Diet, Intelligence and Longevity. Evolutionary Anthropology. 9 (4): 156–185. doi:10.1002/1520-6505(2000)9:4<156::AID-EVAN5>3.0.CO;2-7
http://www.unm.edu/~hkaplan/KaplanHillL ... lution.pdf
2: Gurven, M. and H. Kaplan (2007). Longevity among Hunter-Gatherers: A Cross-Cultural Examination. Population and Development Review 33(2): 321-365. E-ISSN: 17284457
http://www.anth.ucsb.edu/faculty/gurven ... 007pdr.pdf
3: Burger O, Baudisch A, Vaupel JW. Human mortality improvement in evolutionary context. Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18210-4. doi: 10.1073/pnas.1215627109. Epub 2012 Oct 15. PubMed PMID: 23071331; PubMed Central PMCID: PMC3497824.
4: Roberts RO, Roberts LA, Geda YE, Cha RH, Pankratz VS, O'Connor HM, Knopman DS, Petersen RC. Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia. J Alzheimers Dis. 2012;32(2):329-39. doi: 10.3233/JAD-2012-120862. PubMed PMID: 22810099; PubMed Central PMCID: PMC3494735.