You’ve never heard about it before because it isn’t true 
. I disagree with most of Dr. Glorioso’s criticisms of the book, but her discussion of Outlive, metformin, and PD is where I don’t just disagree with her viewpoint, but see a clear departure from the facts and the evidence.
First, there are no “clinical trials pointing to a potential increase in risk of Parkinson’s disease in metformin users.” If there were, it would have been yanked off the market or at least black-boxed years ago: it certainly wouldn’t be the first-line T2D drug in every country on earth. I expect she is misremembering or misunderstanding observational studies such as these, some but not all of which find that metformin use by diabetics is associated with greater risk of PD.
In the Twitter thread reposted by @RapAdmin, she makes an argument from Complex I inhibition, but repeatedly ignores the facts (noted by user HairyBiologist and by geroscientist Jamie Justice) that these studies report Complex I inhibition in the liver, not the brain, and that it is a much weaker inhibitor than rotenone even there. And regardless, that’s a mechanism, not an outcome.
She brings this up in the context of claiming that Attia “has backpedalled on promoting Metformin for longevity in his blog but basically promotes it in this book”. Attia has been saying he doesn’t think metformin is a longevity therapeutic consistently on the blog and in the podcast since at least 2018, and I don’t remember him promoting it in the book. The only entry for metformin in the index is on page 87, which can’t reasonably be said to be ‘promoting’ metformin as a geroprotectant.
Then she says:
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Centenarians and smoking: this is not exactly a point of disagreement but there is a link between longevity and smoking in super centenarians and I don’t think this is an accident. People die increasingly from neurodegenerative diseases in the oldest ages and smoking is linked to less Parkinson’s disease. That’s not to say that we all should smoke- definitely not- smoking causes lung cancer and heart disease. But in people above a certain age- say 80 years old- we should consider creating nicotine pathway drugs or prescribing nicotine patches- my two cents. I think this has been wildly understudied.
Now, I’m glad she backed away from suggesting that peope should smoke to prevent PD, but this is still all based on false premises and failure to account for absolute risk. First, there is no “link between longevity and smoking in super centenarians”: I’m guessing that she’s jumped to conclusions from the singular case of Jeanne Calment. In Nir Barzilai’s centenarians, 59.6% of centenarians had smoked at least 100 cigarettes during their lives, compared to 74.5% of their contemporaries in NHANES I. In Thomas Perls’ New England Centenarian Study, 11% of centenarians reported having smoked more than 2 pack-years during their entire lives, which is substantially less than the general population today, let alone in the mid-20th century when they lived their lives.
She may be thinking of a report on the Okinawan supercentenarians: ""Approximately half (42%) of the supercentenarians had a history of smoking; however, of those participants who did smoke, most began later in life and tended to smoke < 20 cigarettes per day and/or quit by their 70s (data not shown). " Compare this to the general Japanese population:
In the late 1960s, 74% of men and 13% of women reported that they were current smokers, and 13% of men and 2% of women reported that they were former smokers (table 2). In later survey periods, the percentages of current smokers decreased in both sexes and the percentages of former smokers increased. Among current and formers smokers, 25% of men (5842 individuals) and 5% of women (357 individuals) reported that they had started smoking before the age of 20." Impact of smoking on mortality and life expectancy in Japanese smokers: a prospective cohort study - PMC
Beyond that, her whole hypothesis here is inconsistent with the absolute risks involved. Smoking greatly reduces life expectancy by increasing the risk of lung, colorectal, kidney, bladder, and other cancers, as well as CVD and COPD. Yes, there is some epidemiological evidence that smoking reduces the risk of PD, and Parkinson’s disease is a terrible disease, but it is relatively rare and even less commonly kills its victims. Even amongst people aged 85+, only 3% of people have PD — and of course, not everyone with PD dies from PD. The idea that people have a better chance of living to 110 by reducing the risk of a rare disease like PD while greatly increasing the risk of the top two killers and several others of the top 10 is a clear case of an “extraordinary claim requiring extraordinary evidence.”
