If you look at the evidence hierarchy, this study is at the lowest form of evidence (it's a narrative review -i.e expert opinion), they didn't even run a study.
The ultimate study would multiple randomized controlled trials showing sugar/fructose when controlled for calories, causes increased Alheimer's disease. Since we haven't seen that, we should not draw conclusions.
As the saying goes 'correlation does not imply causation'. We don't even have correlation yet, the headline is an overreach.
Agree that it's a poor headline and that the fructose/Alzheimer's hypothesis is quite speculative, but I don't think calling it a "junk study" or gesturing at evidence hierarchies is particularly helpful.
Theory (almost) always precedes evidence, and coming up with a novel, biologically-plausible explanation for a common ailment is absolutely a valid, useful scientific contribution.
Your general point, that drawing firm conclusions would be radically premature, is spot on. I just stiffen up a bit when I encounter "RCT or GTFO" type arguments; where in the world do you think the ideas for which RCT to run come from?
While I agree that these theory based papers are useful, and are often the precursor to experiments, I believe the general understanding of "study has found X" in pop culture is that there is "hard evidence" of the finding being tauted. Theories are risky to place too much credence in without being steeped in the field yourself (is this a theory that most people in the field agree with, or is the one suggesting it an outlier?).
As usual science communication is never done as well as we could all hope, but I personally like this "hierarchy of evidence" approach in understanding if something is ready to be consumed by the general public, rather than requiring further discussion with the scientific community.
Agreed. At this point I am also not willing to just let science off the hook and blame it all on the press: If our smartest people can not find ways to differentiate between ideating and good results in a way that a sensationalist press can't simply ignore, then just maybe they are not trying all that hard.
I wish sci comms practice would have a standard set of terms for stages of development/belief. Here the headline should be something like “theory proposed that …”
Theory (almost) always precedes evidence, and coming up with a novel, biologically-plausible explanation for a common ailment is absolutely a valid, useful scientific contribution.
This is the case in physics and astronomy. People make predictions that are not only untested, but we have to invent equipment to test them.
One of the great early accomplishments in science was when astronomers, observing our Sun, noted an unknown yellow spectral line signature. In 1868, Norman Lockyer predicted that it must be created by a hitherto unknown element, which he named “Helium” after the Greek Titan of the Sun, Helios.
In 1895, two Swedish chemists detected helium in ore samples here on Earth, and in the great tradition of the scientific method, we had a theory, a prediction, and a confirmation of the theory by test.
I'm not sure it's always the case that theory precedes evidence, even in physics. We still have loads of evidence that theory does not explain, dark matter, dark energy and superconductivity being the most well known. Theory is often devised to explain something weird or unexpected that experimentalists observe.
Upon reflection, you’re making an excellent point!
Einstein predicted things we’re still confirming empirically, but then again, he started by asking himself how the speed of light could be constant for every observer, which was the result of an experiment that failed to confirm a different theory.
There's nothing wrong with research like this per se. I think the way it's publicised is the main issue. Broadly I think there are two types of papers: those who are only relevant to other researchers, and those who are interesting to the public as a whole. This is very much in the former category.
how do you expect we will ever get a randomized control trial controlling for fructose in diet?
Your right, but RCT would take how long? 50 years? How can you make people not eat fructose or limit that for 50 years?
Wouldnt call the article junk sciensce. We also need hypothesis builing articles. I think they are proposing a specific mechanism of action about how fructose might cause Alzheimers.
I believe there are other clues also pointing in this direction, which I wont bore you with.
Just want to note, that I think everyone would prefer high powered RCTs, but I dont believe they are feasible to fund and run
We won't. That's why nutrition epidemiology studies are so bad and mostly useless. It's ok to simply say "let's not do this study which we know won't add anything to our knowledge of how nutrition affects health outcomes in real people". See David Chapman for an entertaining review: https://metarationality.com/nutrition
I would say this comment is a bit unfavorable. The study details some metabolic pathways that were recently discovered and are activated by fructose intake. They then explore a hypothesis as to why this could lead to certain outcomes like Alzheimer's.
Not exactly a "junk study." It's step 1 in a chain of studies that could validate this hypothesis.
A review article is not necessarily junk science. This sort of paper is the first step in allowing us to conduct the more interventional studies you recommend.
Trusting a random commenter to dismiss the contents of an article for you seems almost as bad as only reading the headline. In both cases you're putting full faith in someone else to summarize the article in a way that serves their interests more than yours.
You probably still want to at least look at the research yourself, trusting other "off-hand" comments is, uh, ironically, akin to the moral from the "off-hand" parent comment in this case
Right, I never drink straight fruit juice. Those large bottles of orange or apple juice commonly seen in supermarkets I consider dangerous, everyone ought to avoid them.
I predict HN will look on this favorably anyway, because my experience is that a rather large number of them are practitioners of ketogenic or other high-fat low-carb diets and 'fructose bad' may as well be part of their religion.
"...other foods can also stimulate fructose production in the body and induce features of metabolic syndrome. These include foods that provide the glucose substrate for the polyol pathway, such as high glycemic carbohydrates, and foods that stimulate aldose reductase, such as *salty foods and alcohol*. Umami foods (especially processed *red meats, organ meats, shellfish, and beer* that is rich in yeast extracts) also engage the purine degradation pathway leading to uric acid.
The second more proximate factor has been the dramatic rise in the intake of added sugars that contain fructose and glucose, such as *table sugar (sucrose) and high-fructose corn syrup (HFCS)*."
And...
"Interestingly, *whole fruits tend not to activate this pathway* owing to a relatively low fructose content in individual fruits and the presence of neutralizing factors (such as fiber, vitamin C, potassium, and flavanols) and because the small intestine metabolizes some fructose before it reaches the liver and brain."
So basically processed meats, table sugar & high-fructose corn syrup are bad for you. I'm shocked /s
> So basically processed meats, table sugar & high-fructose corn syrup are bad for you. I'm shocked /s
The interesting part of the research is that the authors identified a common player that might progress the development of chronic diseases: high uric acid levels.
Uric acid has historically been associated with gout. But more recently, there has been growing interest in the role of uric acid on the development of chronic diseases like metabolic disease, cardiovascular disease and Alzheimer.
An interesting (imo) pop-medscience video by Dr. David Perlmutter - Uric Acid: A KEY Cause of Weight Gain, Diabetes, Heart Disease & Dementia https://www.youtube.com/watch?v=QZ6jPCcFNa8
Uric acid may be a complex symptomatic expression rather than a cause.
My own journey may reflect this. I suffered from gout and also other worrisome blood work markers that indicated metabolic syndrome. I am now largely vegan, alcohol free and avoid sugar and processed food. I have not had a gout attack for a long time. Then in a recent blood test my uric acid was through the roof. My (excellent) doctor first wanted to raise the amount of allopurinol I was taking but I suffer from side effects and was reluctant. My doctor did some research and found that uric acid levels are raised during periods of weight loss.
With regards to gout, I don't think it's symptomatic: actual uric acid crystals are causing the inflammation that is called gout. The crystals are deposited when the serum level of UA goes above ~400umol/l.
But it's fascinating to hear your story, where you have high UA serum but no gout attack. Were you on 300mg allo or more?
With Alzheimer's and cardiovascular disease, there is much uncertainty, agreed!
My mom got Alzheimer's at age 58. She was trim, ate organic, exercised daily, never smoked or drank, and had a happy social life.
She was always a super light sleeper though, and had her own room because dad would wake her up at night. I wonder whether her brain's lymphatic system was working.
Only other thing that stuck in my mind is not long before her symptoms, she had like six metal fillings removed and replaced with porcelain all at the same time.
Her aunt got it early too and was a health nut juicer for years who lived a healthy lifestyle.
That study was what got me to start routinely flossing after many years of off-and-on attempts. Read it, have flossed basically every day since. I’m aware that they didn’t show a causative link and that evidence for flossing itself is limited, but my gums feel better and don’t bleed anymore, so I figure it can’t be a bad thing either way.
No, I just assume I'll get it in a few years, although neither of her siblings got it.
I'm less healthy than she was at my age (52). My exit plan doesn't involve long term health care insurance, that's for sure.
Mom's still alive at 75, so that's a long run with this disease. I would say it's been about three years since she has declined to that stage where no mentally well person would want to be alive.
I've spent about 10 years doing research into brain metabolism and Alzheimer's. This is an interesting paper! It explains a lot of observed phenomena in the novel context of fructose metabolism. I certainly am convinced that fructose has short-term effects on regional brain activity and whole-body metabolism.
However they don't make great links between fructose and known AD pathology. Beta-amyloid buildup is now pretty convincingly a critical step in the progression of AD. They link a few low-quality papers claiming fructose increases amyloid, but the evidence is pretty weak. Similarly, APOE genotypes are well documented AD risk factors. The authors aren't really able to explain APOE's role in the context of fructose.
Fun read (for me, anyway), but not particularly convincing. Hopefully it provokes some more research to try to fill in some of the missing links.
Just another theory. I swear this domain is mostly people throwing shit at the wall to see what sticks.
I wouldn't be surprised if diet is one of many factors involved. But I really don't see much value by most of the studies at this point. Maybe we'll get to see who's right in a decade or two.
I’ve been saying this for a while - science is great at breaking things down to the atomic level and figuring out what does what, individually. But science sometimes is not so good at the systematic, or synergistic view of multiple variables. We keep trying to break things down to one variable that cures all when it’s probably a mixture of a lot of things + different for people with different genetic.
Some problems are harder to solve than others. It usually stems from a long testing period. Try X, wait. Try Y, wait. If the wait period is decades, you have a problem.
Broadly, statistics and large sample sets are used to combat that.
Human understanding, or lack thereof, for a given problem also contributes to suboptimal theories.
I have fructose malabsorption and when I eat or drink too much of it, I get brain fog (slow reaction, dizziness etc.) for one or two days. Would be interesting to see if fructose malabsorption and Alzheimer's correlate.
Each of our mitochondria need infrared to remove oxidative stress.(inflammation)
They use infrared to do that but we now live inside more and more (especially elderly and sick) and thus we are in a constant crisis of chronic inflammation.
I know it sound new age, but the research is there, like Vit-D with the sun must have sounded ridicule at the time, the need for infrared was not apparent when most people worked outside.
I recently learned about the infrared interaction w/ mitochondria, currently undergoing near-red/low-power laser therapy to recover numbness after fracturing the face.
Anecdata, but haven't people with dementia (not just Alzheimer's) been found to have very strong sugar cravings too? I've heard the term "Diabetes of the brain" for it.
From my own experience, all the syrups that lots of modern food include cause me massive memory and sleep problems.
I do have some gut bacteria imbalances, that might increase the bad effects of sugar, but still, I could not function if I wont avoid added sugars, which is pretty hard task today.
So I'm not surpised by this study, cause I feel it immediatley how the sugar disables my brain.
I've long been curious about understanding the processes involved in creating our processed food and just what sort of chemicals and treatments the raw material pass through to get to what we know and identify on the grocery shelves.
This seems overly cynical. You’re taught as a freshman science student that a research paper should describe its own deficiencies and point to next steps. It’s a pretty basic part of writing about research.
It many ways it is. If your livelihood is based on your research then it's necessary for you to frame your research as important. Existentially important is even better. This way it outcompetes other studies/research/etc for funding from various sources. Why would anyone support your research if it wasn't urgent and important, etc?
This is how incentives work. It's why, for instance, you have gain of function research occurring in many cases. SARS was really interesting but it turns out it was never going to be a large risk for society. Who is going to continue to fund research into it? So, your incentive is to find a way to convince people that fund things that it could in fact find a way to be a global pandemic and gain of function "research" is a great way to do this. Of course you justify it by saying "it could happen and if it did happen then we'd want to know how to prepare for it so lets find the worst ways it could get to that state before it does itself". Now that you've created something terrifying, it's much easier to get gobs of funding for your research.
I’m not saying things are corrupt. Just how they are because of how incentives are structured. For instance, who would fund a climatologist that says climate change probably won’t be too bad based on his models? You’d be far better off trying to find the model that predicts disaster. That will turn heads and open wallets.
Someone with more domain knowledge, does this study hold water? Even perhaps as a reason to look further into the relationship between diet and Alzheimer’s?
I watched an interesting presentation on YouTube about how fructose is digested in the body, its totally different to glucose, and arguably more harmful becuase the liver can only handle so much, there are various metabolic products which also need to be dealt with... So I do believe this may be very plausible.
if you read Johnson's work, it's typically both. Direct fructose consumption as well as the polyol pathway being on and your body converting 'extra' glucose into fructose.
excess fructose (in particular in ultra-processed forms) causes metabolic derangement but consuming too much of those other 3 esp from ultra processed foods, also activates the "switch" leading to endogenous fructose production and more derangement.
The role of sedentarism in all this is somewhat under-explored though.
Probably "Sugar The Bitter Truth" by Lustig 2009 which was "controversial" at the time but more than a decade later its pretty much mainstream.
You're always going to have members of the general public and docs who don't keep upon on continuing nutritional education (snark, there isn't any) saying stuff that was out of date decades ago but I'd say the stuff in that video is pretty much mainstream now.
Unfortunately not, because fructose is also produced endogenously. As mentioned in other comments here, whole fruit consumption seems to not even be the real issue.
Maybe treating AD as a singular disease is confusing researchers into thinking there is a single factor causing this. It’s a spectrum disease, damn do we have to remind them this?
This is an area of active research and it's misleading to claim that there is any kind of consensus that AD is a spectrum disease. If anything, the recent success of anti-amyloid drugs has pushed the consensus the other way.
If you look at the evidence hierarchy, this study is at the lowest form of evidence (it's a narrative review -i.e expert opinion), they didn't even run a study.
The ultimate study would multiple randomized controlled trials showing sugar/fructose when controlled for calories, causes increased Alheimer's disease. Since we haven't seen that, we should not draw conclusions.
As the saying goes 'correlation does not imply causation'. We don't even have correlation yet, the headline is an overreach.