From the Wikipedia page on Curcumin (section Research):
In vitro, curcumin exhibits numerous interference properties which may lead to
misinterpretation of results.[3][6][20] Although curcumin has been assessed in
numerous laboratory and clinical studies, it has no medical uses established by
well-designed clinical research.[21] According to a 2017 review of over 120
studies, curcumin has not been successful in any clinical trial, leading the
authors to conclude that "curcumin is an unstable, reactive, non-bioavailable
compound and, therefore, a highly improbable lead".[3]
The study claims to have studied a bioavailable forom of curcumin, Theracumin® but it uses a very restricted interpretation of "bioavailability":
The use of adjuvants that block curcumin metabolism, or nanoparticles, liposomes,
phospholipid complexes, and other strategies have improved its bioavailability somewhat,
but only as defined as increased curcumin blood levels8,64–66 with minimum effects on
curcumin availability to the brain.
The study also notes its sample was small:
The relatively small sample size in this study warrants caution in interpreting
our results and limits their generalizability.
It just doesn't sound like their results are going to stand the test of time.
None of your criticisms from wikipedia pertain to this publication. The paragraph is essentially making the argument that a randomized, double blind (DB), placebo controlled (PC) clinical trial (RCT) is unlikely to show that curcurmin is effective. yet, the published article is exactly that, and shows a statistically measurable impact on a clinically meaningful endpoint: a direct refutation of the paragraph.
the fact the "interference properties" and being an "unstable, reactive, non-bioavailable compound" is subsumed by the study design.
claims to have studied a bioavailable form of curcumin
This is not really relevant to the claim or conclusions. could it be that the bioavailability matters? maybe. could it be that curcurmin is a trick molecule to study? yes. but come what may, this is direct evidence (not proof) of a cause-effect relationship between this treatment and the outcome.
the only thing this effects is the chance that other forms of curcurmin will be comparable (and it might have consequences for regulatory status by the FDA).
The study also notes its sample was small
This is a very weak criticism when the study is positive (i.e. shows an effect). when the sample size (and statistical power) of the study is small, you need a BIG EFFECT SIZE to be positive. The fact that the trial was positive actually means that it's more likely to be clinically important, because a big effect size means it protects memory in a dramatic way. This is like penicillin: in the pre-antibiotic era, how many cases of pneumonia do you need to treat in order to be satisfied that penicillin is effective? Not bloody many, because the effect size is so dramatic. Likewise for parachutes. few are the therapies that fall into this category, but when you have an inkling that one does following a DB, PC, RCT, you better pay attention.
So does it need to be replicated? definitely. does the sponsorship matter? definitely; they could have cheated in some way. until then does it make sense to prescribe this to seniors, or encourage them to increase curcurmin in their diet? quite possibly, given the presumably low rate of adverse effects.
Bottom line: this study is not the end-all be-all of curcurmin and memory, but there is legitimate early evidence that the emperor has clothes.
When a small sample size produces a big effect, it does not mean you can be more confident in the effect!
All things equal, you'd expect confidence intervals / credible regions to be very large.
Another way to say this, is that since the measurement error is large, you expect spurious findings that result from something like p-hacking to be large (they have to be to be significant).
>> None of your criticisms from wikipedia pertain to this publication. The paragraph is essentially making the argument that a randomized, double blind (DB), placebo controlled (PC) clinical trial (RCT) is unlikely to show that curcurmin is effective. yet, the published article is exactly that, and shows a statistically measurable impact on a clinically meaningful endpoint: a direct refutation of the paragraph.
I think, if there are solid reasons to believe that studies on curcumin will not turn up any useful results and then a study finds results it calls significant, the chances are that either that study is not designed very well, or its results are not significant, despite the claims of the authors.
Apologies in advance for the controversial example, but this reminds me of the controversy about Daryl Bem's parapsychology research a few years ago- the author claimed his study was methodologically unassailable, but of course he was making an absurd claim (essentially, that people can receive information from the future via ESP).
>Because curcumin's anti-inflammatory properties may protect the brain from neurodegeneration
My very first question was: Please provide a possible physiological pathway for this. I'm so glad it was answered in the very first sentence. So many of these "Superfood does X" studies are just trials with 10 people over a month, with no explanation as to __how__ it could possibly happen. It significantly increases the skepticism I have whenever something like this comes up
I also did not know Turmeric had anti-inflammatory properties. I guess I have reading to do.
Also interesting that they used (what seems to be) a name brand supplement instead of Turmeric
I am a neurologist. this is actually the exact opposite of what you should care about, which is "does it work to treat ___"
In this trial, and 99% of other trials, there is no mechanism provided by the study, only a measurement of causality (which is the same thing as effectiveness).
The authors may think they know based on other, prior, basic science research (as they are postulating here), but it does not affect the conclusions of the trial ( whether they do or don't (or even if they are wrong).
Obviously it's intellectually satisfying to understand WHY, but it's not as important as "is it true?"
I am having trouble accepting your argument. Judea Pearl presents [0] the debate over whether smoking causes cancer as an illustration for why correlation is not sufficient. Two plausible, contradictory, models ('smoking causes cancer', 'no it doesn't, something else does') could not be settled by observing correlations. The debate was resolved through the addition of an explanatory mechanism, and a test of the mechanism's influence. Pearl, and others, have worked on the mathematical machinery necessary to examine this kind of causality.
Obviously you don't understand HN.. everyone here is a "very smart software engineer" and knows far better than a simpleton like you with your decades of medical training and experience.
The problem with “is this true?” Investigations is that there are tons of potential pitfalls and a combination of experimental limitations, poor academic incentives, and insufficient statistical and scientific training make this very hard to do well. I think it’s bad science, that will one day retrospectively be viewed as invalid scientific method.
I think the way to combat this is to avoid studies that solely attempt to demonstrate an effect, but to complement that part of an investigation with additional studies that demonstrate a plausible explanation. This reduces the risk of false positives and increases our confidence in the result.
The additional studies could take the form (for example) of deliberately intervening such that the effect should be manipulated by the intervention in a predictable and measurable way. Essentially, come at the hypothesis “from another angle”.
As far as neurology and psychiatry go, if we're not asking "how?", it's because we're very far from comprehending. Our brains are exceedingly complicated. If two neurons can ride a bicycle, imagine the complexity arising in a system with billions and billions.
More generally, however, a plausible mechanism is a great aid in determining the potential value of further researching a correlation because as we all know, correlation != causation, but correlation + mechanism pretty much is causation, which means correlation + plausible mechanism is very interesting. It's not wrong to ask "how?" here, though it might not yield much given the nature of the field. Certainly, anti-inflammatory properties can plausibly have positive effects on the psyche, so that's a mechanism worth some looking into.
For all the claims of bioavailability, I was surprised to see that Theracumin(R) doesn't seem to contain piperine[1] or any perines (which are usually in curry powder courtesy of black pepper). The 90mg dosage also seemed low, I have been taking 500mg of 95% extract daily for a couple of years.
Turmeric has helped me quite a bit with my inflamed joints after learning about it at a yoga ashram. Now I cook a lot with it. What i have noticed though is that supplements do nothing for me. I only feel a difference when it's fresh powder or even better ground from a root.
I have done several experiments where I stopped taking it. Every time my joints got worse and then better after resuming cooking with Turmeric.
To add to your experience, i have managed to treat several severe tooth/gum abscesses with fresh sliced tumeric root steeped for 4-12 weeks in brazilian sugarcane rum (51 pinga). It kills the pain almost instantly and after a few days of use, the infection disappears. I now swish it in my mouth once a month or so as a preventative measure.
It's important to note that there are more than 10 varieties of tumeric, and have markedly different morphologies.
Also: growing conditions or perhaps some other factor affects the depth of the yellow color of a crop, as well as smell, which seem to be indicators of potency.
Lately, particularly since the recent judicial decision in India regarding the intellectual property rights of tumeric which denied a patent to a western company, I've seen general attitudes toward 'curcumin' in western academia revert their opinion about it's potential.
i dont expect any study that isolates the curcumin molecule (which ks widely known to be non-bioavailable on its own) to be very effective.
furthermore (conspriacy theory warning) considering the lack of scruples of the bio-based businesses (med agri gen chem), i wouldn't be surprised to see medically inert or even toxic varieties of 'unprofitable' and/or 'competitor' plants to flood the market in places where tumeric isn't grown amongst traditional small farmers. just a thought, and fits the monsanto narrative in the us and india.
I post this whenever HN brings up a comment about supplements -- but I created a site to help track people trying out a lot of supplements and how it impacted health and sleep.
HN and QuantifiedSelfers find this as a niche site to record correlations and habits for self improvement.
More it more I'm learning that inflammation is a huge problem in modern health. I'd be very interested in a list of anti-inflammatory foods, supplements and behaviors.
Beware. We don't know that the inflammation is not compensatory. Since we know its purpose IS to be compensatory, it seems more reasonable to default to it being compensatory, than the original problem; or better, to withhold our judgement.
Inflammation is a symptom of most auto-immune diseases. Usually the inflammation is caused by your own auto-immune system attacking your healthy cells.
Some examples Uveitis (eye inflammation), Crohn's (bowels), Reumatoid Artritis (Joints). Usually these diseases come in pairs, so some people are just more susceptible to whatever causes these diseases. Right now there is no cure but in the last decades huge progress has been made in suppressing these diseases using biologics, but they have the side effect of suppressing your immune system which may be dangerous.
I agree. "How" is a difficult question to answer, and involves basic research. "X does Y" studies need a hypothesis, a bunch of test subjects, and some statistical wrangling. Far easier than basic research. I'm now at a point to take all statistical studies with a pinch of salt. Molecular studies are more interesting and while micro and may miss the macro picture, are more promising.
Not to say it's not useful (a plausible method of action + weak evidence is more suggestive that further study is needed than weak evidence alone, and that understanding could lead to further developments), but the question of does this work is far more important, and can be answered without knowing the how.
I vaguely remember reading that the physiology of acetaminophen is still not completely understood. I doubt we will be lucky to figure this one out quickly. I also remember reading that the level of dementia in India is much lower than western nations and turmeric was thought to be part of the reason for that.
Given what we’re learning about the impact of gut microbiome on CNS, immune system, and other systems I wonder if the GI effect is it, but with secondary effects related to activity of bacterial colonies.
Gut biome is insanely important, I've had digestive issues for over a year and it's been depressing that they couldn't find the cause.
I finally gave up waiting and decided to experiment myself, started drinking a yakult every morning and last thing at night, within two weeks things started... Moving and now 6 weeks in its like it used to be, bloatings gone, regular as clockwork, energy levels are up and I generally feel better.
I still have other issues that are more serious but the medication handles those ok.
I started taking vitamin D a few weeks before that as well and that seemed to help as well.
Small study, probably not preregistered (didn't find anything about it in the description). Likely Publication Bias or p-hacking. I'm starting to get interested when it's been independently replicated.
Almost entirely irrelevant, provided it's properly powered--and based on the effect size and p-values, it is. Furthermore, for an 18 month trial, 40 people is larger than most.
> probably not preregistered
I mean, true, and we should definitely promote pre-reg, but, 1. so few are preregistered that I'm not sure it's prudent to disregard a study based on this and 2. it's an academic study, neither a clinical trial nor a public-health decree--not a typical study type that necessitates pre-registration.
> Likely Publication Bias or p-hacking.
What? You're arrived at this conclusion based on... the fact that it's "small" and you couldn't find preregistration about it?
> I'm starting to get interested when it's been independently replicated.
The University of California, Los Angeles, owns a U.S. patent (6,274,119) entitled “Methods for Labeling ß-Amyloid Plaques and Neurofibrillary Tangles”, which has been licensed to TauMark, LLC. Drs. Small, Satyamurthy, Huang, and Barrio are among the inventors and have financial interest in TauMark, LLC. Dr. Small also reports having served as an advisor to and/or having received lecture fees from Allergan, Argentum, Axovant, Cogniciti, Forum Pharmaceuticals, Herbalife, Janssen, Lundbeck, Lilly, Novartis, Otsuka, and Pfizer. Dr. Heber reports receiving consulting fees from Herbalife, and the McCormick Science Institute. The manufacturer of Theracurmin, Theravalues Corporation, provided the Theracurmin and placebo for the trial, funds for laboratory testing of blood curcumin levels, and funds for Dr. Small's travel to the 2017 Alzheimer's Association International Conference for presentation of the findings.
it's not turmeric, it's curcumin, which is about 2% of turmeric by mass (so, you'd need to eat ~4.5g turmeric daily to match study doses)
Typical Indian cooking uses turmeric in pretty much everything. I wouldn't be surprised if daily consumption of turmeric is very close to the figures you mentioned.
I don't' work in the field so I find it hard to interpret these studies. What's your opinion about the size of improvements in practice?
For example, How meaningful is the 20.3 point difference in Buschke SRT test?
Cohen's d (mean difference divided by SD) above 0.60 with the memory or attention seems good (73 % of the people who take the dose get above the mean test score). But difference that is detectable in a test is not telling me how big the effect would be in the daily performance unless I'm familiar with the test.
It was registered as a clinical trial (https://clinicaltrials.gov/ct2/show/NCT01383161?term=NCT0138...). If you are concerned about p-hacking and replicability, what should worry you is that the outcome measures posted during registration are rather vague, i.e. ".. show less evidence of cognitive decline (as measured with neuropsychological assessments)"
At baseline, they performed an extensive neuropsychologist test battery, including a bunch of subtests:
-Trail Making Test A
-WAIS-III Digit Symbol Substitution
-WAIS-III Block Design Test
-Rey-Osterrieth Complex Figure Test (copy)
-Trail Making Test B
-Stroop Interference
-F.A.S.
-Buschke-Fuld Selective Reminding Test [SRT]
-Wechsler Memory Scale-3rd Edition [WMS-III]
-Verbal Paired Associations I
-Benton Visual Retention Test
-Buschke-Fuld SRT
-Rey-Osterrieth Complex Figure Test [recall]
-WMS-III Verbal Paired Associations II
-Boston Naming Test
-Animal Naming Test
The outcome measures they report are:
-TMT-A
-SRT
-BVMT-R
I would be _very_ surprised if those were the only tests they performed at followup after a 18 month (expensive) clinical trial. If these measures had been specified as the only outcome measures of interest, noone would question the results. But, when it was not registered, and when no other measures are reported, not even in the supplementary, the reader is left to wonder why that is.
Excellent point. Outcome measures should have been more clearly defined in pre-registration. As it was done, p-hacking and selective reporting were still possible.
Great "credibility check". There should be a "nutriction facts table" for scientific papers quoted at articles. Sample size, preregistration, replication, p-value.
At least a practice to include that in the abstract
Maybe along the lines of 'A statistical definition for reproducibility and replicability'? I think there are more attributes to be included, but it seems like a good place to start on a 'nutrition label' for papers.
The problem you describe is a real one, but a bit different than the other criticism raised here so far.
Chocolate has the Mars Company and other Big Sugar companies behind it pushing for justifying chocolate as a "health food" in the public mind. It is very obvious that they are wiling to distort the truth for better sales; people who can ease their conscious about eating unhealthy sweets buy more chocolate[0]. There might be some real effect to eating raw cocoa, but that does not really translate to your average chocolate bar with insane amounts of fat and sugar.
Tea/Coffee is kind of similar, as would be the "drink x glasses of water per day"-advice, which is a distortion of science by bottled water companies (fruits, vegetables and other food contains a ton of water already).
For this reason I also don't buy that salt is safe: there are very strong vested interests in the food industry that want salt to be (considered) safe to sell more food, whereas I cannot see a comparable bias on the "eat less salt"-side.
For this research the situation seems to be have some of the mentioned problems, but not to the same degree:
On the one hand, that tumeric has an in-vitro effect is pretty well established. The issue is that the normal form we put on our food is probably not absorbed in a dosage that has a significant effect. However, this was a trial with a bio-available form, in a high enough dosage, so that obvious flaw is out of the picture.
On the other hand, that bio-available form is a product, so the company behind it wants it to be effective. Still, Big Pharma is under more scrutiny than Big Sugar, so I have cautious hopes this might actually work out in the end (and it won't be sold in the form of calorie-rich sweets at least).
Admittedly, I'm biased here: my grandmother on my mother's side, and my grandfather on my father's side both had Alzheimers (or something very similar to it at least). My parents are now their late sixties, I would really like to see them stay healthy and happy for a few more decades.
Aren’t we? People are living longer than ever before. The issue is in determining effect size. I’m sure some amount of all those things you mentioned is “good” in some sense, but in what quantity and for how long?
It's great to be skeptical, but it's really lame to be skeptical and lazy. It's a terrible combination that causes patients not to trust their doctors.
This is becoming an increasingly worrying trend - to bunk any analysis with a comment on 'small sample size, biases' that somehow moves to the top of the comment pile.
Statistically, there is no such thing as a 'small sample size', in isolation. It is always related to the power and effect that the researchers want to work with.
Moreover, even if a study is statistically insignificant, it DOES NOT mean that the opposite conclusion is true. It might often merit some further examination of cultural and historical trends. In this case, for instance, turmeric has been used for medicinal properties in Asian cultures for centuries. Theories of evolution suggest that this wouldn't be the case (and it would've died a natural death), if there wasn't some merit.
>In this case, for instance, turmeric has been used for medicinal properties in Asian cultures for centuries. Theories of evolution suggest that this wouldn't be the case (and it would've died a natural death), if there wasn't some merit.
Lots of things that are completely useless have been used for thousands of years for their medicinal purposes. The evolution argument only holds if there were some negative effects here. Anything that doesn't do harm to the body can easily integrate into the huge body of knowledge called superstition. Eating it is tasty and doesn't hurt, there's nothing more needed to explain that Asian cultures have it as a medicinal herb.
If it for example was good for you but caused somewhat unpleasant side-effects, your evolutionary argument might have more merit. Anything that works as well as homeopathy (it doesn't), but doesn't harm either (like homeopathy), won't be sorted out.
> In this case, for instance, turmeric has been used for medicinal properties in Asian cultures for centuries. Theories of evolution suggest that this wouldn't be the case (and it would've died a natural death), if there wasn't some merit.
That is utter nonsense. To give just one counter-example, bloodletting was used for millennia for conditions where it’s completely ineffective (and, in fact, actively harmful: bloodletting has killed scores of people). In fact, you simply can’t apply an argument from evolution here. Evolution doesn’t optimise for “goodness”. It optimises something (and only over the long term). That “something” can often be positively detrimental to other outcomes, and even to general fitness (e.g. the laryngeal nerve).
Statistics makes basic assumptions that are false. For example, most things don't fit a bell curve.
These assumptions are more relevant in small sample sizes. Making them inherently unreliable. What's missing is not a p-value, but an estimate for the uncertainty around that p-value.
It's possible, but I think (not that I'm an expert) that this is not the first piece of evidence to suggest this. A year or two was recently speaking with a researcher who studies Alzheimer's and he had told me about how in cultures where more curry and turmeric was consumed there was significantly less Alzherimer's. I'll try to find a source for this and update my comment.
Not only is that anecdotal, but even if it's true it is correlative in the weakest sense. There are undoubtedly countless other features for which "cultures" (how does one define this concretely btw) with low Alzheimer's rates also are outliers.
Examine.com has a page for curcumin. They cite 5 sources with notable impacts on reducing depression, but they summarize with this:
"Curcumin seems to be somewhat more effective than placebo in reducing symptoms of depression. It may take 2-3 months to see any outcomes. Skepticism is warranted though, as the studies comparing curcumin to placebo were not well designed and produced effect sizes not too far apart, even though the differences were statistically significant."
agree that replication is important and that it's too early to believe fully, but when a study size is small and you still find a difference, then it implies the effect size is large.
If you meet statistical significance, then diminishing n means increasing clinical significance.
> but when a study size is small and you still find a difference, then it implies the effect size is large
That’s only true if it holds across multiple studies. Otherwise it might simply be random variability. By your argument, a study with n=4 that showed an effect would imply a huge effect size. No. It implies that the measured signal is highly variable, and that you got lucky on 1:3 odds. Check out regression towards the mean [1].
(Note that if you’ve got a good underlying model of the variability, n=4 can work. In fact, it’s routinely done in specific applications, such as transcriptomics. But even there it’s far from ideal, and it’s supported by a stringent error model.)
Effect size is the amount of change that has been observed, in this case the ability to memorize things.
Significance is the probability of the result being coincidence. So "highly significant" only means "most probably not coincidence".
That means you can have a "highly significant" result where the actual result (= effect size) is tiny.
In study design, both are related: The higher the number of test persons, the easier it is to archive significance. Therefore, proper design would be to first guesstimate (based on existing literature etc.) the effect size, then define the minimum number of test persons necessary.
Personal anecdote: was born and brought up in south India and my grandma used to make me drink turmeric + ground black pepper milk every night. It was a standard practice to serve it with black pepper, even though I’m sure they didn’t really know about bioavailability. Kids were forced to drink it when they have the flu.
Used to hate it as a kid, but of late I’ve been looking to replace one coffee/tea with turmeric milk.
> was born and brought up in south India and my grandma used to make me drink turmeric + ground black pepper milk every night
I grew up in a part of South India with a fairly high natural background radiation (thorium, mostly) and I did wonder if the practice boosted survival via accidental cancer protection from an alpha decay environment.
Natural selection is weird because the goal of taking turmeric might have nothing to do with the survival advantages.
About a half-teaspoon or so of turmeric, and about a teaspoon of black pepper. A teaspoon of black pepper might be a bit aggressive, so adjust it to suit your taste, but my mom seems to think lots of pepper is necessary to reduce coughing/phlegm when you're down with a cold.
Fun fact - tumeric was the trigger for India creating a patent fighting engine around Indian traditional medicine (Ayurveda and unaani) including a gene bank and international legal force around biopiracy.
It's an interesting result, but they do note that the subpopulation is somewhat self-selected: "Only approximately 15% of the screened volunteers were included in the study, and our recruitment method yielded a sample of motivated, educated, physically healthy subjects concerned about age-related memory problems. The sample, therefore, was not representative of the general population. "
There’s a difference between bioavailability and half life. Metabolic enzyme inhibition increases half life due to decreased hepatic metabolism of certain drugs. Bioavailability is how much of a drug your body absorbs from the initial dose.
Very interesting to see this posted. In Japan its ingredients are used in an anti-hangover drink, this youtube video https://youtu.be/Ij_aJI5O9Rs goes somewhat deeper into it, where the poster tried a combination of it and pepper to strengthen the effect.
Note: this was a relatively small sample (40 total, split in half for placebo/not), who were elderly people who already have "mild" memory problems, and given a concentrated turmeric derivative rather than just sprinkling it over food.
In summary: very cool, and I'd offer these curcumin supplements to anyone 50+ but sprinkling turmeric on your breakfast cereal ain't going to do much for high schoolers.
Actually the age range was 51-84, so middle plus old age, not all "elderly". Normal people flourish and are in their prime around 50.
Volunteers had "objective cognitive performance scores and clinical histories consistent with normal aging or MCI (i.e., mild neurocognitive disorder) and inconsistent with dementia (i.e., major neurocognitive disorder)." [emphasis added]
"Normal people flourish and are in their prime around 50."
This is false. The only advantage people in their fifties have is experience. Your body is past its peak physically and mentally. People flourishing in their fifties are by and large reaping the benefits of things done in their younger decades, not because they are peaking.
I'm not saying that someone that is 50 years old is decrepit, but ask nearly any academic and they'll tell you they were better when they were younger. Ask nearly any athlete (ultramarathoners being an exception) and they'll tell you they were better when they were younger.
> Normal people flourish and are in their prime around 50
How do you mean? I don't think most people in their 50s would describe themselves as being "in their prime".
For example, ELO ratings of Chess players tend to decline in their 30s[1]. For NBA players, their "prime" is typically the late 20s, with performance declining in their 30s.
There are side effects to be aware of taking curcumin together with other medications:
"Medications for diabetes (Antidiabetes drugs)
Interaction Rating: Moderate Be cautious with this combination.
Talk with your health provider.
Turmeric might decrease blood sugar in people with type 2 diabetes. Diabetes medications are also used to lower blood sugar. Taking turmeric along with diabetes medications might cause your blood sugar to go too low. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.
Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others."
Turmeric might slow blood clotting. Taking turmeric along with medications that also slow clotting might increase the chances of bruising and bleeding.
Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates)
Interaction Rating: Moderate Be cautious with this combination.
Talk with your health provider.
Some medications are changed and broken down by the liver. Turmeric might decrease how quickly the liver breaks down some medications. Taking turmeric along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking turmeric talk to your healthcare provider if you take any medications that are changed by the liver.
Some medications that are changed by the liver include some calcium channel blockers (diltiazem, nicardipine, verapamil), chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), glucocorticoids, alfentanil (Alfenta), cisapride (Propulsid), fentanyl (Sublimaze), lidocaine (Xylocaine), losartan (Cozaar), fexofenadine (Allegra), midazolam (Versed), and others."
Readit News
the fact the "interference properties" and being an "unstable, reactive, non-bioavailable compound" is subsumed by the study design.
This is not really relevant to the claim or conclusions. could it be that the bioavailability matters? maybe. could it be that curcurmin is a trick molecule to study? yes. but come what may, this is direct evidence (not proof) of a cause-effect relationship between this treatment and the outcome.the only thing this effects is the chance that other forms of curcurmin will be comparable (and it might have consequences for regulatory status by the FDA).
This is a very weak criticism when the study is positive (i.e. shows an effect). when the sample size (and statistical power) of the study is small, you need a BIG EFFECT SIZE to be positive. The fact that the trial was positive actually means that it's more likely to be clinically important, because a big effect size means it protects memory in a dramatic way. This is like penicillin: in the pre-antibiotic era, how many cases of pneumonia do you need to treat in order to be satisfied that penicillin is effective? Not bloody many, because the effect size is so dramatic. Likewise for parachutes. few are the therapies that fall into this category, but when you have an inkling that one does following a DB, PC, RCT, you better pay attention.So does it need to be replicated? definitely. does the sponsorship matter? definitely; they could have cheated in some way. until then does it make sense to prescribe this to seniors, or encourage them to increase curcurmin in their diet? quite possibly, given the presumably low rate of adverse effects.
Bottom line: this study is not the end-all be-all of curcurmin and memory, but there is legitimate early evidence that the emperor has clothes.
edits: mainly spelling, formatting
All things equal, you'd expect confidence intervals / credible regions to be very large.
Another way to say this, is that since the measurement error is large, you expect spurious findings that result from something like p-hacking to be large (they have to be to be significant).
I think, if there are solid reasons to believe that studies on curcumin will not turn up any useful results and then a study finds results it calls significant, the chances are that either that study is not designed very well, or its results are not significant, despite the claims of the authors.
Apologies in advance for the controversial example, but this reminds me of the controversy about Daryl Bem's parapsychology research a few years ago- the author claimed his study was methodologically unassailable, but of course he was making an absurd claim (essentially, that people can receive information from the future via ESP).
Edit: removed cruft.
My very first question was: Please provide a possible physiological pathway for this. I'm so glad it was answered in the very first sentence. So many of these "Superfood does X" studies are just trials with 10 people over a month, with no explanation as to __how__ it could possibly happen. It significantly increases the skepticism I have whenever something like this comes up
I also did not know Turmeric had anti-inflammatory properties. I guess I have reading to do.
Also interesting that they used (what seems to be) a name brand supplement instead of Turmeric
In this trial, and 99% of other trials, there is no mechanism provided by the study, only a measurement of causality (which is the same thing as effectiveness).
The authors may think they know based on other, prior, basic science research (as they are postulating here), but it does not affect the conclusions of the trial ( whether they do or don't (or even if they are wrong).
Obviously it's intellectually satisfying to understand WHY, but it's not as important as "is it true?"
[0] http://singapore.cs.ucla.edu/LECTURE/lecture_sec3.htm
I think the way to combat this is to avoid studies that solely attempt to demonstrate an effect, but to complement that part of an investigation with additional studies that demonstrate a plausible explanation. This reduces the risk of false positives and increases our confidence in the result.
The additional studies could take the form (for example) of deliberately intervening such that the effect should be manipulated by the intervention in a predictable and measurable way. Essentially, come at the hypothesis “from another angle”.
More generally, however, a plausible mechanism is a great aid in determining the potential value of further researching a correlation because as we all know, correlation != causation, but correlation + mechanism pretty much is causation, which means correlation + plausible mechanism is very interesting. It's not wrong to ask "how?" here, though it might not yield much given the nature of the field. Certainly, anti-inflammatory properties can plausibly have positive effects on the psyche, so that's a mechanism worth some looking into.
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For example, How meaningful is the 20.3 point difference in Buschke SRT test? Is it noticeable in daily life, or just something detected in testing.
1: https://www.ncbi.nlm.nih.gov/pubmed/9619120
I have done several experiments where I stopped taking it. Every time my joints got worse and then better after resuming cooking with Turmeric.
No idea how it works but it seems to work.
It's important to note that there are more than 10 varieties of tumeric, and have markedly different morphologies.
Also: growing conditions or perhaps some other factor affects the depth of the yellow color of a crop, as well as smell, which seem to be indicators of potency.
Lately, particularly since the recent judicial decision in India regarding the intellectual property rights of tumeric which denied a patent to a western company, I've seen general attitudes toward 'curcumin' in western academia revert their opinion about it's potential.
i dont expect any study that isolates the curcumin molecule (which ks widely known to be non-bioavailable on its own) to be very effective.
furthermore (conspriacy theory warning) considering the lack of scruples of the bio-based businesses (med agri gen chem), i wouldn't be surprised to see medically inert or even toxic varieties of 'unprofitable' and/or 'competitor' plants to flood the market in places where tumeric isn't grown amongst traditional small farmers. just a thought, and fits the monsanto narrative in the us and india.
Also funny that some men on TRT take turmeric(with some black pepper) to lessen the amount of estrogen converted from testosterone.
HN and QuantifiedSelfers find this as a niche site to record correlations and habits for self improvement.
https://betterself.io/ (Open sourced)
Some examples Uveitis (eye inflammation), Crohn's (bowels), Reumatoid Artritis (Joints). Usually these diseases come in pairs, so some people are just more susceptible to whatever causes these diseases. Right now there is no cure but in the last decades huge progress has been made in suppressing these diseases using biologics, but they have the side effect of suppressing your immune system which may be dangerous.
Till date, it has not failed once to cure the inflammation/infection/pain. The infection is gone within a day or atmost a couple of days.
As they usually do on their own.
I finally gave up waiting and decided to experiment myself, started drinking a yakult every morning and last thing at night, within two weeks things started... Moving and now 6 weeks in its like it used to be, bloatings gone, regular as clockwork, energy levels are up and I generally feel better.
I still have other issues that are more serious but the medication handles those ok.
I started taking vitamin D a few weeks before that as well and that seemed to help as well.
https://www.sciencedirect.com/science/article/pii/S000629520...
Almost entirely irrelevant, provided it's properly powered--and based on the effect size and p-values, it is. Furthermore, for an 18 month trial, 40 people is larger than most.
> probably not preregistered
I mean, true, and we should definitely promote pre-reg, but, 1. so few are preregistered that I'm not sure it's prudent to disregard a study based on this and 2. it's an academic study, neither a clinical trial nor a public-health decree--not a typical study type that necessitates pre-registration.
> Likely Publication Bias or p-hacking.
What? You're arrived at this conclusion based on... the fact that it's "small" and you couldn't find preregistration about it?
> I'm starting to get interested when it's been independently replicated.
Yeah, if only there were another trial that showed a positive cognitive effect of bioavailable curcumin... https://www.ncbi.nlm.nih.gov/pubmed/25277322
I mean, the title of this post is by far the most wrong thing about this article, as...
1. it's not turmeric, it's curcumin, which is about 2% of turmeric by mass (so, you'd need to eat ~4.5g turmeric daily to match study doses).
2. curcumin doesn't even have any reasonable bioavilability by itself, so they're using a bioavailable analogue.
The University of California, Los Angeles, owns a U.S. patent (6,274,119) entitled “Methods for Labeling ß-Amyloid Plaques and Neurofibrillary Tangles”, which has been licensed to TauMark, LLC. Drs. Small, Satyamurthy, Huang, and Barrio are among the inventors and have financial interest in TauMark, LLC. Dr. Small also reports having served as an advisor to and/or having received lecture fees from Allergan, Argentum, Axovant, Cogniciti, Forum Pharmaceuticals, Herbalife, Janssen, Lundbeck, Lilly, Novartis, Otsuka, and Pfizer. Dr. Heber reports receiving consulting fees from Herbalife, and the McCormick Science Institute. The manufacturer of Theracurmin, Theravalues Corporation, provided the Theracurmin and placebo for the trial, funds for laboratory testing of blood curcumin levels, and funds for Dr. Small's travel to the 2017 Alzheimer's Association International Conference for presentation of the findings.
>Almost entirely irrelevant, provided it's properly powered--and based on the effect size and p-values, it is.
Sorry to state this so strongly but I feel it's important to point out that this is misinformation of the most egregious kind.
There is no examination of statistical power in this article whatsoever so there is no basis for your claim that this study is properly powered.
Large effect sizes are not evidence of adequate statistical power. Quite the opposite is true. E.g. See this article: https://www.nature.com/articles/nrn3475/figures/5
'Effect inflation is worst for small, low-powered studies, which can only detect effects that happen to be large.'
Typical Indian cooking uses turmeric in pretty much everything. I wouldn't be surprised if daily consumption of turmeric is very close to the figures you mentioned.
I don't' work in the field so I find it hard to interpret these studies. What's your opinion about the size of improvements in practice?
For example, How meaningful is the 20.3 point difference in Buschke SRT test?
Cohen's d (mean difference divided by SD) above 0.60 with the memory or attention seems good (73 % of the people who take the dose get above the mean test score). But difference that is detectable in a test is not telling me how big the effect would be in the daily performance unless I'm familiar with the test.
At baseline, they performed an extensive neuropsychologist test battery, including a bunch of subtests:
The outcome measures they report are: I would be _very_ surprised if those were the only tests they performed at followup after a 18 month (expensive) clinical trial. If these measures had been specified as the only outcome measures of interest, noone would question the results. But, when it was not registered, and when no other measures are reported, not even in the supplementary, the reader is left to wonder why that is.At least a practice to include that in the abstract
[0] https://www.biorxiv.org/content/early/2016/07/29/066803
[1] https://cran.r-project.org/web/packages/scifigure/index.html
Chocolate has the Mars Company and other Big Sugar companies behind it pushing for justifying chocolate as a "health food" in the public mind. It is very obvious that they are wiling to distort the truth for better sales; people who can ease their conscious about eating unhealthy sweets buy more chocolate[0]. There might be some real effect to eating raw cocoa, but that does not really translate to your average chocolate bar with insane amounts of fat and sugar.
Tea/Coffee is kind of similar, as would be the "drink x glasses of water per day"-advice, which is a distortion of science by bottled water companies (fruits, vegetables and other food contains a ton of water already).
For this reason I also don't buy that salt is safe: there are very strong vested interests in the food industry that want salt to be (considered) safe to sell more food, whereas I cannot see a comparable bias on the "eat less salt"-side.
For this research the situation seems to be have some of the mentioned problems, but not to the same degree:
On the one hand, that tumeric has an in-vitro effect is pretty well established. The issue is that the normal form we put on our food is probably not absorbed in a dosage that has a significant effect. However, this was a trial with a bio-available form, in a high enough dosage, so that obvious flaw is out of the picture.
On the other hand, that bio-available form is a product, so the company behind it wants it to be effective. Still, Big Pharma is under more scrutiny than Big Sugar, so I have cautious hopes this might actually work out in the end (and it won't be sold in the form of calorie-rich sweets at least).
Admittedly, I'm biased here: my grandmother on my mother's side, and my grandfather on my father's side both had Alzheimers (or something very similar to it at least). My parents are now their late sixties, I would really like to see them stay healthy and happy for a few more decades.
[0] https://www.vox.com/science-and-health/2017/10/18/15995478/c...
https://clinicaltrials.gov/ct2/show/NCT01383161?cond=NCT0138...
It's great to be skeptical, but it's really lame to be skeptical and lazy. It's a terrible combination that causes patients not to trust their doctors.
Statistically, there is no such thing as a 'small sample size', in isolation. It is always related to the power and effect that the researchers want to work with.
Moreover, even if a study is statistically insignificant, it DOES NOT mean that the opposite conclusion is true. It might often merit some further examination of cultural and historical trends. In this case, for instance, turmeric has been used for medicinal properties in Asian cultures for centuries. Theories of evolution suggest that this wouldn't be the case (and it would've died a natural death), if there wasn't some merit.
Lots of things that are completely useless have been used for thousands of years for their medicinal purposes. The evolution argument only holds if there were some negative effects here. Anything that doesn't do harm to the body can easily integrate into the huge body of knowledge called superstition. Eating it is tasty and doesn't hurt, there's nothing more needed to explain that Asian cultures have it as a medicinal herb.
If it for example was good for you but caused somewhat unpleasant side-effects, your evolutionary argument might have more merit. Anything that works as well as homeopathy (it doesn't), but doesn't harm either (like homeopathy), won't be sorted out.
That is utter nonsense. To give just one counter-example, bloodletting was used for millennia for conditions where it’s completely ineffective (and, in fact, actively harmful: bloodletting has killed scores of people). In fact, you simply can’t apply an argument from evolution here. Evolution doesn’t optimise for “goodness”. It optimises something (and only over the long term). That “something” can often be positively detrimental to other outcomes, and even to general fitness (e.g. the laryngeal nerve).
These assumptions are more relevant in small sample sizes. Making them inherently unreliable. What's missing is not a p-value, but an estimate for the uncertainty around that p-value.
Here is a great demonstration of how correlation does not imply causation: http://www.tylervigen.com/spurious-correlations.
"Curcumin seems to be somewhat more effective than placebo in reducing symptoms of depression. It may take 2-3 months to see any outcomes. Skepticism is warranted though, as the studies comparing curcumin to placebo were not well designed and produced effect sizes not too far apart, even though the differences were statistically significant."
https://examine.com/supplements/curcumin/#hem-depression
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If you meet statistical significance, then diminishing n means increasing clinical significance.
That’s only true if it holds across multiple studies. Otherwise it might simply be random variability. By your argument, a study with n=4 that showed an effect would imply a huge effect size. No. It implies that the measured signal is highly variable, and that you got lucky on 1:3 odds. Check out regression towards the mean [1].
(Note that if you’ve got a good underlying model of the variability, n=4 can work. In fact, it’s routinely done in specific applications, such as transcriptomics. But even there it’s far from ideal, and it’s supported by a stringent error model.)
[1] https://en.wikipedia.org/wiki/Regression_toward_the_mean
Significance is the probability of the result being coincidence. So "highly significant" only means "most probably not coincidence".
That means you can have a "highly significant" result where the actual result (= effect size) is tiny.
In study design, both are related: The higher the number of test persons, the easier it is to archive significance. Therefore, proper design would be to first guesstimate (based on existing literature etc.) the effect size, then define the minimum number of test persons necessary.
Used to hate it as a kid, but of late I’ve been looking to replace one coffee/tea with turmeric milk.
I grew up in a part of South India with a fairly high natural background radiation (thorium, mostly) and I did wonder if the practice boosted survival via accidental cancer protection from an alpha decay environment.
Natural selection is weird because the goal of taking turmeric might have nothing to do with the survival advantages.
I tried searching but I cant find a study where apartment builings in Japan were inadvertently built using steel laced with radioactive elements.
People (10000) were living in them for decades. Statistical analysis on them showed lower affinity for cancer related deaseses.
1 tsp of ground turmeric powder
A pinch or two ground black pepper
If you’re not used to turmeric, I’d suggest starting with half tsp as it’s got quite a strong flavour (especially when not cooked with other spices)
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We now have something called Traditional Knowledge Digital Library (TKDL) - http://www.tkdl.res.in/tkdl/langdefault/common/Home.asp?GL=E...
http://www.mondaq.com/india/x/586384/Patent/Traditional+Know...
https://examine.com/supplements/curcumin/
It's an interesting result, but they do note that the subpopulation is somewhat self-selected: "Only approximately 15% of the screened volunteers were included in the study, and our recruitment method yielded a sample of motivated, educated, physically healthy subjects concerned about age-related memory problems. The sample, therefore, was not representative of the general population. "
Also, black pepper inhibits CYP3A4, not 450.
https://www.youtube.com/watch?v=lr4MmmWQtZM
In summary: very cool, and I'd offer these curcumin supplements to anyone 50+ but sprinkling turmeric on your breakfast cereal ain't going to do much for high schoolers.
Volunteers had "objective cognitive performance scores and clinical histories consistent with normal aging or MCI (i.e., mild neurocognitive disorder) and inconsistent with dementia (i.e., major neurocognitive disorder)." [emphasis added]
This is false. The only advantage people in their fifties have is experience. Your body is past its peak physically and mentally. People flourishing in their fifties are by and large reaping the benefits of things done in their younger decades, not because they are peaking.
I'm not saying that someone that is 50 years old is decrepit, but ask nearly any academic and they'll tell you they were better when they were younger. Ask nearly any athlete (ultramarathoners being an exception) and they'll tell you they were better when they were younger.
How do you mean? I don't think most people in their 50s would describe themselves as being "in their prime".
For example, ELO ratings of Chess players tend to decline in their 30s[1]. For NBA players, their "prime" is typically the late 20s, with performance declining in their 30s.
1. https://www.chess.com/blog/LionChessLtd/age-vs-elo---your-ba...
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"Medications for diabetes (Antidiabetes drugs) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider. Turmeric might decrease blood sugar in people with type 2 diabetes. Diabetes medications are also used to lower blood sugar. Taking turmeric along with diabetes medications might cause your blood sugar to go too low. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.
Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others."
Turmeric might slow blood clotting. Taking turmeric along with medications that also slow clotting might increase the chances of bruising and bleeding.
Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider. Some medications are changed and broken down by the liver. Turmeric might decrease how quickly the liver breaks down some medications. Taking turmeric along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking turmeric talk to your healthcare provider if you take any medications that are changed by the liver.
Some medications that are changed by the liver include some calcium channel blockers (diltiazem, nicardipine, verapamil), chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), glucocorticoids, alfentanil (Alfenta), cisapride (Propulsid), fentanyl (Sublimaze), lidocaine (Xylocaine), losartan (Cozaar), fexofenadine (Allegra), midazolam (Versed), and others."
https://www.rxlist.com/turmeric/supplements.htm#Interactions