Carotenoids Are Associated With A Younger Epigenetic Age And Reduced All-Cause Mortality Risk
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- Опубліковано 13 бер 2021
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Papers referenced in the video:
DNA methylation GrimAge strongly predicts lifespan and healthspan:
pubmed.ncbi.nlm.nih.gov/30669...
GrimAge outperforms other epigenetic clocks in the prediction of age-related clinical phenotypes and all-cause mortality:
pubmed.ncbi.nlm.nih.gov/33211...
Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies:
pubmed.ncbi.nlm.nih.gov/30475...
Albumin is included as a biological age predictor:
www.ncbi.nlm.nih.gov/pmc/arti...
www.ncbi.nlm.nih.gov/pmc/arti...
www.ncbi.nlm.nih.gov/pmc/arti...
pubmed.ncbi.nlm.nih.gov/30993...
Age-related change data for albumin:
pubmed.ncbi.nlm.nih.gov/26071...
Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages:
www.nature.com/articles/s4146... - Наука та технологія
Great video! Fun fact: Goji berries are by far the richest source for Zeaxanthin, with orange Paprika coming second. Also, worth mentioning are Carotenoids coming from Saffron, which together with Lutein and Zeaxanthin are very important for the eyes.
No wonder man, i knew this long ago as corelation with longevity from the blue zones and their diet, sure they eat plant rich diets but all of them have either MASSIVE amounts of sweetpotatoes, carrots, aprictors, pumpkins, leafy greens, thanks for the data, i was so happy to see this video!!
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I ate loads of carotenoids for 18 years (plus small amounts of liver for 4 years) and got skin conditions. Last 3 years reduced the carotenoids significantly and reversed decades of problems.
There is likely an upper limit, even from whole foods. Similarly, my blood test data is not optimal with the "more is better" approach:
ua-cam.com/video/Q3PXBl82uTk/v-deo.html
"Vitamin a" is literally poisoning people.
Madness.
Incredible video. Thanks so much for sharing this information. I wish I had discovered your channel much sooner. My diet has been pretty good, but lately it has been getting a little soft around the edges. This is just what I need to kick me in the butt and get it back on point again. This is an incredible channel and the sort of thing we need more of. Thanks!
Thanks. Very valuable research.
Very interesting, thank you.
Thanks doctor very interesting 🙂
Thank you this formula can be followed easily at any age!
Thanks for sharing. I’ll be eating these foods more often!
Thanks Gary. As I mentioned in the video, eating more carotenoids looks like an easy way to reduce epigenetic age, and to reduce all-cause mortality risk! (assuming causation, which hasn't been evaluated in RCTs, yet)
@@conqueragingordietrying1797 any additional research on carotenoid astaxanthin? I heard it activates FOX03 longevity gene.
@@diamond_s Not yet, but thanks for that suggestion!
3:02 Orange-fleshed sweet potato is also rich in beta-cryptoxanthin ( up to 21.2 µg/g dry basis).
Yep, thanks @thomasmuller1850. I find carrots are more satiating, so I get the majority from red bell pepper instead.
I went looking for a correlation between albumin and carotenoids in studies. I could only find one potentially relevant study. Association of Serum Carotenoid Levels With Urinary Albumin Excretion in a General Japanese Population: The Yakumo Study.
"Adjusted ORs for albuminuria among women in the highest tertiles of serum β-carotene (OR, 0.45; 95% CI, 0.20-0.98) and provitamin A (OR, 0.45; 95% CI, 0.20-0.97) were significantly lower as compared with those for women in the lowest tertile. There were no associations between serum carotenoids and albuminuria in men."
Perhaps carotenoids did not raise your albumin levels, and perhaps carotenoids do not raise albumin levels in men. (We only have one study, so it's hard to jump to a conclusion) Perhaps the decline in all cause mortality from carotenoids is also independent of albumin levels.
Thanks for making this video!
Thanks Jack Buaer. Albuminuria is a different condition (poor kidney function) than the amounts in serum, which reflects liver function and inflammation, but good try nonetheless!
@@conqueragingordietrying1797 would a chronic inflammatory liver condition be expected to cause lower serum albumin?
@@Avital4414 Unfortunately, yes, as albumin is produced by the liver.
that was truly surprising... are there hypotheses about mechanisms? Actions on immune system, buffer capacity of serum, and the like? Carotenoids not only have an effect on Albumin... could be an epiphenomenon, such as lycopene protective against prostate cancer
Watched this again after reading a fringe theory on vitamin A. Have you looked at preformed vitamin A as well, like retinol or rentinoic acid?
Net net: Eating vegetables and fruits are good for you.
That's something your grandmother has been telling you for years...
Grandma didn't tell me to eat over 400g of carrots, 400g of broccoli, 300g of bell pepper and over 100g of spinach per day though. That's hard to incorporate in a normal day.
@@thomasmuller1850 Neither did mine. People generally prefer cooked food because it is easier to digest, and make its components easier to absorb. If one starts with the quantity of food described in your post and were to cook them, it would be doable, but I think 400g of carrots would be excessive, although, one would get more out of 100 grams of cooked carrots as compared to 400 g of raw. 100 g of spinach would all but disappear if cooked.
What about studies claiming increased risk of lung cancer( even agressive prostate cancer) and breast cancer, people consuming too much carotenoids?
That's for supplemental carotenoids, and more specifically, lung cancer risk for beta-carotene supplementation in smokers. I've yet to see a study showing increased disease or mortality risk from eating too many vegetables...
Great work! Do you think blending (no juicing) will destroy any of the benefits carotenoids?
Thanks Sean Olivas! Is there data that blending destroys the carotenoid's benefits? I eat a bunch of raw carotenoids (carrots, spinach, watermelon, red bell peppers), so I should be good there. Alternatively, that makes me wonder about the apigenin in parsley, which I eat blended.
I would say that the chemical structure itself is stable enough to survive all the enzymes you will set free by blending... As for their role of H+\e- scavenging \ transfer capability that should remain intact, if you drink it soon after blending
Good stuff, thank you. Do you happen to know whether (or to what extent) carotenoids are damaged by cooking?
I haven't looked into that, but I get most of my carotenoids raw (carrots, watermelon, red bell pepper, parsley, spinach (sometimes cooked).
Don't cook them
@@meyerhans2125 Can you please post that/those link(s)? It would provide value to the audience...
Thanks @Abdel-Ilah BENAHMED. Can you please post some of those paper links?
@@conqueragingordietrying1797 pubmed.ncbi.nlm.nih.gov/19083456/
Lutein gets destroyed when you cook it.
I recently discovered I have a SNP that down regulates Carotenoid conversion by 70%. Since caratenoids are plant based and not therefore bioavailable to humans, I'm assuming the benefit comes from high Vit A causing increases in autophagy, protection from tumor growth, etc and therefore the same benefit can be found by consuming liver.
Any thoughts for those of us who don't benefit from consuming Plants?
Blood test, find the meats or other foods that best optimize as many circulating biomarkers as possible, but also other biomarkers like blood pressure, for ex.
Would you mention the SNP ID you're referring to?
@@kkostadinof I actually have a couple in the Vit A pathway, so estimated the 70% down regulation. Plus a DVR defect + viral issues from Mono, so my fat soluble vitamin D3 is also a mess... Not to mention the MTHFR SNPs.
As a result, I'm now eating about 80% pastured red (fatty)meat, by caloric weight, and feeling MUCH better. That doesn't mean I don't like my fruits and vegs, but I no longer have the inflammation and appear younger (skin, hair, body comp, libido) than as a vegetarian.
And, my blood labs are all good, if you don't mind explaining to MDs that high cholesterol correlates to longevity (immune fx).
I also work to keep my O6:O3 ratios between 4:1 and 1:1 using +/- fresh fish eggs to adjust O3s according to my lipid panels. This may also help my fat soluble Vitamin concentrations, but I'm always on the lookout for new ways to improve my metabolics and neurological function.
Here are a couple of papers on the topic of Carotenoids / SNPs / Bioavailability:
pubmed.ncbi.nlm.nih.gov/19103647/
pubmed.ncbi.nlm.nih.gov/22147584/
pubmed.ncbi.nlm.nih.gov/30277929/
pubmed.ncbi.nlm.nih.gov/30032230/
@@ybigirl Many thanks for the detailed response!
@@ybigirl homozygous rs12934922 T:T too (and homozygous for A1298C) feel much better eating liver at least once per week
Hi Michael. Thanks again for YAGV (yet another great video). Remind us again how long you have been eating this level of veggies?
BTW, a little unrelated perhaps.. do we need to limit the amount of fructose we get in a day? For example I love dates, and they are pretty high in fiber so I thought I was set. But then I read about various health problems related to too high fructose & apparently 2 dates have the same amount of fructose as a can of Coke. Yikes.
Makes me wish I was in Morocco again where you can get a variety of dates. Some of them are not so sweet and more fibrous.
Thanks Matthew. I like the YAGV acronym, haha that's great. I've been eating that level of veggies for ~the past 6 years, and only because it seems to best optimize most of my circulating biomarkers.
In terms of limiting fructose, I'd say that there's likely a threshold where above a certain level is bad for health. About 7 years ago I tried low-fat veganism for a year, and I ate about double the amount of fruit that I do now. That sent my TGs up and my HDL down, so from my experience, there's definitely an amount of fructose that can be bad for health, even on a high FV diet. I wouldn't worry about 2 dates/day, as they have fiber and other nutrients, whereas soda has calories and nothing else. For this past blood test, my average date intake was 38g/d, which is basically 2 large Medjool dates/day.
Michael, I am trying to achieve the same result from different foods. I have imputed the limited in Optimiser based on your food intakes and obtain the following targets. Are these the targets I should be aiming for:
Log2 Alpha Carotene 14627.4 ug
Log2 beta Carotene 48957.4 ug
Lycopene 6077 ug
Log 2 Lutein and Zeaxanthin) 23207.2 ug
Log 2 beta crptoxanthin 1647.1 ug
Thanks
Hey Michael, yep, that's in the ballpark for my regular intake. Note that amounts that may work for me may not for others-I'd suggest regular blood testing, and titrating carotenoid amounts to see if it's net beneficial for your biomarkers.
how many carrots a day is safe ? think can overdosed on it too
How about retinol? Isn't retinol the "active" form of vitamin A and carotenoids only precursors? Unless vegan should one focus on carotenoids or retinol? Animal sources are richer in retinol and is much easier to meet/surpass the RDA compared to carotenoids. I haven't look into it but somewhat reminds of the never-ending discussions regarding n3:n6 ratio, which does not make any sense if you get EPA/DHA from animal sources instead of ALA from plants. Just to clarify, I'm not anti-plant based or pro-animal foods, just trying to understand the reasoning and biological function.
That's a different question. The studies in the video looked at carotenoids, which are obtained from plants. I'm not anti-meat or pro-plants, but that's what they looked at.
Carotenoid are not only precursors to Vitamin A (retinol). Lycopene (for example) has been found to have anti-cancer effects, that are not related to whether or not lycopene is converted to retinol; which I don't even think it is.
I also read about a study that found that lycopene combined with beta carotene prevents the oxidation of LDL cholesterol, thereby reducing the buildup of cholesterol in the arteries. And that was due to the antioxidant effects of beta carotene and lycopene, not due to any conversion of those carotenoids to Vitamin A.
What is the risk that these correlations only indicate that the GrimAge model picked up on younger people in the training data eating more carotenoids than older people in the training data? Would not be surprising considering that vegetables have been promoted aggressively as healthy food(s) since a few decades, thus nudging younger people towards increased consumption of such.
Also, is it warranted to believe that higher albumin values indicate something positive about the individuals current health state *forecast*? Do you have age-stratified correlations data on albumin vs ACM? Considering that albumin is a serum transport protein, and according to Wikipedia it binds: water, cations (such as Ca2+, Na+ and K+), fatty acids, hormones, bilirubin, thyroxine (T4) *and pharmaceuticals (including barbiturates)*. Considering that last point, that it also binds and transports pharmaceuticals, we might warrant to question if singularly looking at albumin values should be done with much more care. We could also alternatively consider serum albumin as indicating just general healthy nutritional and protein status in underlying individuals to the training data. Thus an individual with healthy general nutritional status, and specifically healthy protein status, would be able to more efficiently and healthily vary serum albumin values to manage environmentally and physiologically stressed health states. Something those with less healthy general nutritional and protein status might not be able to produce to same degree, thus contributing to the increased ACM in the model training data populations resulting in the models picking up on individuals with bad general nutritional and specifically protein status by the albumin proxy.
I suspect it is merely association because carotenoids may stress thyroid function. Perhaps there is an upper limit.
Processed food diets are low in carotenoids. So carotenoids correlate to a healthier diet and so on.
About lutein and zeaxanthin, they are reported to block autophagy. So time your spinach intake!)
Citation on lutei. and zeaxanthin autophagy blocker?
@@ramiv9953 a valid question my friend Archback. It's actually only lutein that has this effect; "Lutein Attenuates Both Apoptosis and Autophagy upon Cobalt (II) Chloride-Induced Hypoxia in Rat Műller Cells".
Any data on increasing carotenoid blood content with supplements? Don't really find it feasible to eat 400g of carrots per day consistently.
If you're going to supplement, it's important to measure blood biomarkers (or other health-related metrics) to make sure that the dose is beneficial, not benign or harmful. Eating veggies to increase blood carotenoids is the lowest risk, but potentially maximal gain-strategy.
There’s a huge hole in the logic of this video and the paper on which it derives its conclusion.
Can anyone think of some fast food or junk food that will provide high levels of carotenoids?
No? Neither can I, which means the people with low-carotenoids are people who don’t eat carrots or foods that contain carrots i.e. people on an unhealthy diet.
Conversely, people who have high carotenoids are all eating carrots i.e. are probably health conscious people.
Thus this video and Lu 2019 have not sufficiently accounted for the healthy person confounder.
It also means Dr Lustgarten’s evidence on the correlation with his albumen data is also inadmissible, because he’s the perfect example of a healthy person confounder.
I dare say we could look at any of his longevity biomarkers and they would all equally trend spectacularly with carrots.
The correlation with carrots and longevity might be more compelling if there were papers that devised interventions to provide a mechanistic explanation of the longevity benefits of carrots, other than falling back on the 1980s Linus Pauling chestnut of antioxidant theory.
While there is the possibility for healthy user bias, the study in the video looked at circulating levels of carotenoids, which was associated with a younger biological age and reduced all-cause mortality risk. Is that proof of causation? No, but there are no RCTs that have directly tested that hypothesis. While we wait for those studies, adding some or more carotenoids into our diet is the lowest risk strategy for potential improvements in these health-related metrics.
Correct. Correlation isn't the same as cause and effect. It's why clinical trials are so hard to design, and often challenged.
Isn't low albumen caused by inflammation.
How do you eat 400g+ carrots a day? Smoothie? Rotating cooking recipes?
Ha, raw. It's relatively easy, I can eat more, but beta-carotene is also correlated with higher glucose in my data, so ~400g/day it is!
@@conqueragingordietrying1797 Hey Michael, I was just looking on Amazon, and there are powdered organic versions of each of the beta-carotenoid-containing foods which you have mentioned in the above video. Roughly speaking, couldn't we just consume say, 40 grams of powdered carrots, rather than 400 grams of fresh carrots?...
@@ThaUnseenTruth Food that is dehydrated has a lower nutrient density than the whole, fresh food. So while you may enrich for a particular nutrient, the whole sum of the dried food will be nutritionally inferior to the whole food. For example, see this analysis that I did for raisins vs. grapes:
michaellustgarten.com/2014/07/27/grapes-vs-raisins-a-nutritional-analysis/
@@ThaUnseenTruth Alternatively, you can do the experiment: blood test to establish a baseline, eat 40g of dried carrots for a few blood tests, then do a few blood tests with 400g of carrots/d.
Beta carotene effect p38 and akt so it must be why. Good to know cause I dont wanna use it yet, due to running rapa and fisetin, and beta carotene is a strong anti oxidant so I need to stop it 20 days before due to extremely long half life .. but now it seems like it wont interfere
Have fun popping pills of unstudied chemicals in humans which have zero proof of longevity benefits. You're rolling a dice.
For 60 years we have been searching for a magic pill that will make us live longer and to date none has been found. Name one. It's all guessing and speculation.
@@wanderingdoc5075 what are you talking about? We have 1000s of pubmed studies on vitamins. Ur ridiculous
@@wanderingdoc5075 SGLT2 inhibitors
@@wanderingdoc5075 It cannot be just one magic bullet. Aging is too complex to be solved by a single intervention.
Might low sodium V8 be a convenient way to supplement carotenoids?
V8 isn't whole food-ideally, getting them from veggies would be optimal, but probably some is better than none with V8.
@@conqueragingordietrying1797 I'll make mine a V8. (I think that was the old commercial but interestingly there is nothing I could find searching.)
@@conqueragingordietrying1797 Seriously though, V8 or supplements when you can't get the fresh stuff?
Do you really eat a pound of carrots per day?
How? Raw, cooked or juiced? I was feeling good about getting 900 g/week cooked.
A pound of broccoli a day I can understand. I love that stuff, but carrots, not so much.
Ha, I do. Exclusively raw, I don't like them cooked. You lose the fiber with juicing, so I never do that. It's not a competition against me-the key is discovering the food amounts that optimize your biomarkers, and that's likely different for each of us.
@@conqueragingordietrying1797 I agree that juicing is a waste and cooked carrots aren't my favorite either, but I would think that carotenoid in carrots are more bioavailable in cooked vs raw. Of course, if more of the carotenoids are absorbed in one's small intestines, there would be less making it to one's microbiome in one's large intestines so it's difficult to know for sure which is more beneficial without RCS's.
BTW, thank you for you quick response. Regards jc
Thanks Joe, I almost always respond to comments! Ha, now is the time for that, before the channel gets too big to respond to them all...
@@conqueragingordietrying1797 It's good content and your channel deserves more attention. Good luck gaining traction.
Wouldnt your skin turn orange color eating that many carrots every single day?
Mine hasn't, maybe that would be true for others
I want to know how he eats 25 cups of vegetables, plus has to get carb intake
After I returned to Sg from studying in London I ate 2 big papayas a day having missed it. It wasn’t long before I started to turn proverbial yellow! Fingers as if I was a long time smoker. Not great look on face either. Doctor advised total avoidance of yellow/orange fruit and vegetable. Took about 2 years to lose colour leach! As I was 18 I can’t speak to younger epigenetic age.
This is probably a naive question, but wouldn't it be possible that the carotenoids are associated with younger epigenetic age just because chidren, ahem, probably like carrots more than any other veggetables, while older people find them hard on their teeth? Since epigenetic age strongly correlates with chronological age.
Or have they discovered that association based on individuals of equal chronological age?
The average age for the people in the epigenetic age-carotenoid correlation study was ~64y (see www.aging-us.com/article/101684/text), so it's children didn't drive that correlation.
@@conqueragingordietrying1797 Thanks; the women were 58-71 years, so no children indeed.
But I suppose, fundamentally, that such an obvious error could not have happened because the authors in the paper you linked, in "Results / Diet, education, and life style factors", under Fig.6, wrote :
"All (age-adjusted) DNAm-based biomarkers correlate with plasma biomarkers measuring vegetable consumption [...] "
So this "age-adjusted" must be the key. I guess it means that for each person, they subtracted a part that increases (or even proportional) with chronologial age from the respective DNAm biomarker value or epigenetic age; so that what's left is a value relative to the average person of same chronological age. (For example, your age-adjusted aging-dot-ai bio-age would be about "-18" years).
Now this can indeed be used to discuss influence of carrots :)
Does that include vitamin A?
Nope, that's a potential topic for a different video
Is 4.8 g/dL a good Albumin level?
Yes!
@@conqueragingordietrying1797Thanks for the reply! Good to hear that has always been my level on every lab result the past 13 years or so for me.
All the info is in here: www.ncbi.nlm.nih.gov/pmc/articles/PMC6539799
Possibly mediated by foxo I guess
Is there published data for FOXO with beta-carotene-/albumin?
I dunno. My epigenetic age was 22-23 as predicted by your calculator (real age of 35). My albumin is always 5.2 and I hardly eat any veggies. Tough to make correlations like you're doing. Maybe my high albumin is from sauna use, optimal body comp, genetics, protein consumption. We don't know. Any evidence that a lower epigenetic age is associated with a lower risk of spontaneous events like cancer or some anatomical abnormality you can develop at any time? I'm skeptical we can use non-causative (correlation at best) data to make these predictions. Something as stupid as eating more vegetables can result in a (genetically or otherwise) suseptible individual to develop an autoimmune disease from the myriad of antinutrients or thousands of other chemicals in plants. As an example. We don't know.
The calculator linked in my Excel file is for Levine's Phenotypic Age, which calculates biological age based on clinical biomarkers, not epigenetics. Levine has a separate epigenetic test with the same name, though (DNAm PhenoAge). Nonetheless, I'm guessing that your biological age with the clinical biomarkers is 22-23y, which is great!
For me, higher beta-carotene is correlated with higher albumin. I can't say if that will work for others, but when considering that most people don't eat many vegetables, it's an easy experiment. Alternatively, what works for one may not work for another, as your data shows. Congrats on the high albumin, the key now is to make sure it stays relatively high and doesn't decrease during aging.
I disagree that it's tough to make correlations like I'm doing. First, I I identify them in my data (wherever they're present), and either raise/reduce intake to see if it is indeed causative. For most of the circulating biomarkers, I see diet-dependent effects, and improvements over time, not the opposite. So this approach works for me, and it would definitely work for others with enough tracking of diet, blood biomarkers, exercise metrics, etc. The alternative is to do nothing, and that's not good enough for me.
Chances of developing an autoimmune condition are far higher with modern industrial farming which laces animal products with tons of hormones, chemicals and other foreign to human physiology substances than you would get from eating veggies. Give your head a shake if you believe otherwise.
@Nutritiondetective for the full truth