How to Slow Brain Aging by Two Years

How to Slow Brain Aging by Two Years
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The consumption of blueberries and strawberries is associated with delayed cognitive aging by as much as 2.5 years—thought to be because of brain-localizing anthocyanin phytonutrients, as shown on functional MRI scans.

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

“A plant-based diet is thought to have played a significant role in human evolution and the consumption of whole plant foods…[and even just] extracts has repeatedly been associated with… decreased risk [of] aging-related diseases.” And, by healthy aging, I’m not talking preventing wrinkles. What about protecting our brain?

“Two of the most dreaded consequences of dementia with aging are problems moving around and difficulty remembering things. Dementia robs older adults of their independence, control, and identity.” What can we do about it?

Well, fruits and vegetables help reduce the risk of other chronic diseases. Might they work for brain diseases, as well? “There has been a proliferation of recent interest in plant polyphenols as agents in the treatment of dementia.” There are 4,000 different kinds found “ubiquitously in foods of plant origin.” But, berries are packed with them, possessing “powerful antioxidant and anti-inflammatory properties.” And, there’s a subset of a subset called anthocyanidins—natural blue-purple pigments “uniquely and specifically capable of both crossing the blood-brain barrier and localizing inside brain regions involved in learning and memory…” And, that’s where we need it.

The brain takes up less than like 2% of the body weight, but may burn up to 50% of the body’s fuel, creating a potential firestorm of free radicals. So, maybe these brain-seeking phytonutrients in berries could fight oxidation, inflammation, and increase blood flow. So, this raised a “thought-provoking idea.” Maybe a “nutritional intervention with blueberries may be [beneficial] in forestalling or even reversing the neurological changes associated with aging.”

So, did researchers give blueberries to people, and see what happened? No. As I noted in an earlier video, they gave blueberries to rats. It would be a decade before the first human trial. But, it worked! Blueberry supplementation improves memory in older adults, suggesting that “consistent supplementation with blueberries may offer an approach to forestall or mitigate” brain degeneration with age.

What other blue/purple foods can we try? Concord grape juice had a similar benefit, improving verbal learning—suggesting that “supplementation with purple grape juice may enhance cognitive function [in] older adults with early memory decline.” Why use juice, and not whole Concord grapes? Because then, you couldn’t design a placebo that looked and tasted exactly the same, to rule out the very real and powerful placebo effect. And, also, because it was funded by the Welch’s grape juice company.

This effect was confirmed, though, in a follow-up study, showing for the first time an increase in neural activation in parts of our brain associated with memory using functional MRI scans. But, this brain scan study was tiny—just four people in each group. And, same problem with the blueberry study; it just had nine people in it.

Why haven’t large population-based studies been done? Because we haven’t had good databases on where these phytonutrients are found. We know how much vitamin C is in a blueberry, but not how much anthocyanidin—until now. The Harvard Nurses’ Health Study followed the cognitive function of more than 16,000 women for years, and found that “[H]igher, long-term consumption of berries [was associated with] significantly slower rates of cognitive decline in this cohort of older women, even after careful consideration of confounding by socioeconomic status”—meaning even after taking into account the fact that rich people eat more berries. The first population-based evidence that “greater intakes of blueberries and strawberries…were highly associated with slower rates of cognitive decline,” and not just by a little bit. “The magnitude of associations…were equivalent to the cognitive differences that [one might observe] in women up to 2.5 years apart in age.” In other words, “women with higher intake of berries…appeared to have delayed cognitive aging by as much as 2.5 years.”

Why not just take some kind of anthocyanidin supplement? Because there hasn’t been a single study that found any kind of cognitive benefit just giving these single phytonutrients. In fact, the opposite. “Whole blueberries appear to be more effective than individual components, showing that the whole is greater than the sum of its parts. These findings potentially have substantial public health implications, as increasing berry intake represents a fairly simple dietary modification to test in older adults for maintaining [brain function].”

Please consider volunteering to help out on the site.

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

“A plant-based diet is thought to have played a significant role in human evolution and the consumption of whole plant foods…[and even just] extracts has repeatedly been associated with… decreased risk [of] aging-related diseases.” And, by healthy aging, I’m not talking preventing wrinkles. What about protecting our brain?

“Two of the most dreaded consequences of dementia with aging are problems moving around and difficulty remembering things. Dementia robs older adults of their independence, control, and identity.” What can we do about it?

Well, fruits and vegetables help reduce the risk of other chronic diseases. Might they work for brain diseases, as well? “There has been a proliferation of recent interest in plant polyphenols as agents in the treatment of dementia.” There are 4,000 different kinds found “ubiquitously in foods of plant origin.” But, berries are packed with them, possessing “powerful antioxidant and anti-inflammatory properties.” And, there’s a subset of a subset called anthocyanidins—natural blue-purple pigments “uniquely and specifically capable of both crossing the blood-brain barrier and localizing inside brain regions involved in learning and memory…” And, that’s where we need it.

The brain takes up less than like 2% of the body weight, but may burn up to 50% of the body’s fuel, creating a potential firestorm of free radicals. So, maybe these brain-seeking phytonutrients in berries could fight oxidation, inflammation, and increase blood flow. So, this raised a “thought-provoking idea.” Maybe a “nutritional intervention with blueberries may be [beneficial] in forestalling or even reversing the neurological changes associated with aging.”

So, did researchers give blueberries to people, and see what happened? No. As I noted in an earlier video, they gave blueberries to rats. It would be a decade before the first human trial. But, it worked! Blueberry supplementation improves memory in older adults, suggesting that “consistent supplementation with blueberries may offer an approach to forestall or mitigate” brain degeneration with age.

What other blue/purple foods can we try? Concord grape juice had a similar benefit, improving verbal learning—suggesting that “supplementation with purple grape juice may enhance cognitive function [in] older adults with early memory decline.” Why use juice, and not whole Concord grapes? Because then, you couldn’t design a placebo that looked and tasted exactly the same, to rule out the very real and powerful placebo effect. And, also, because it was funded by the Welch’s grape juice company.

This effect was confirmed, though, in a follow-up study, showing for the first time an increase in neural activation in parts of our brain associated with memory using functional MRI scans. But, this brain scan study was tiny—just four people in each group. And, same problem with the blueberry study; it just had nine people in it.

Why haven’t large population-based studies been done? Because we haven’t had good databases on where these phytonutrients are found. We know how much vitamin C is in a blueberry, but not how much anthocyanidin—until now. The Harvard Nurses’ Health Study followed the cognitive function of more than 16,000 women for years, and found that “[H]igher, long-term consumption of berries [was associated with] significantly slower rates of cognitive decline in this cohort of older women, even after careful consideration of confounding by socioeconomic status”—meaning even after taking into account the fact that rich people eat more berries. The first population-based evidence that “greater intakes of blueberries and strawberries…were highly associated with slower rates of cognitive decline,” and not just by a little bit. “The magnitude of associations…were equivalent to the cognitive differences that [one might observe] in women up to 2.5 years apart in age.” In other words, “women with higher intake of berries…appeared to have delayed cognitive aging by as much as 2.5 years.”

Why not just take some kind of anthocyanidin supplement? Because there hasn’t been a single study that found any kind of cognitive benefit just giving these single phytonutrients. In fact, the opposite. “Whole blueberries appear to be more effective than individual components, showing that the whole is greater than the sum of its parts. These findings potentially have substantial public health implications, as increasing berry intake represents a fairly simple dietary modification to test in older adults for maintaining [brain function].”

Please consider volunteering to help out on the site.

Images thanks to Minnesota Historical Society and Chiot’s Run via flickr

95 responses to “How to Slow Brain Aging by Two Years

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  1. Berry interesting! Maybe that’s why as a child I wanted Frankenberry and not Count Chocula as a breakfast cereal.
    Really! ;-)




    2
    1. I believe that frozen are as, if not more, nutritious. I buy whatever’s on sale—fresh or frozen. One thing I’ve found is that you can buy frozen wild blueberries. They’re smaller than the cultivated ones, but very tasty. Tangy frozen cranberries are also very nice with steel-cut oats, a few walnuts, and some unsweetened soy milk.




      1
      1. I agree they are indeed smaller than the cultivated ones. Wyman’s of Maine “fresh frozen wild blueberries” are often on sale at our local Stop&Shop. Yes, they are “very tasty.” I sure don’t scarf down 8 oz. a day of them, though — like Steve here!

        Maybe I’ll look into frozen cranberries, too. (Yeah, and I also do the soymilk — despite the bad press it often gets. Sometimes y’gotta take chances in life. ;-)




        0
        1. Agreed. I think if you worry too much about your food you offset all the good that food is doing. Besides, my soy milk is unsweetened, organic, and made from whole soybeans. Though sometimes I am bad and use TVP-type soy in soups. Oh well, it hasn’t killed me ye..ghfciuekolaaaaaaaaaaaaaaaaaa




          1
          1. The only that concerns me about soy is that it can, apparently, block phytonutrient absorption. Remember this Dr. Gregor video: http://nutritionfacts.org/video/soymilk-suppression/

            But perhaps this only happens with tea? I decided not to take any chances and switch to Almond milk. I would rather use soy because it is lower in fat. But I really don’t want to take any chances with blocking phytonutrient uptake.




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            1. Thanks Ben. Yeah, it is a bit of a concern. I don’t use a lot of soy milk—usually on my morning quinoa or steel-cut oats. That video leaves the phytonutrient absorption question a bit open, so I’ll continue the status quo for now. Besides, everything I eat is teeming with phytonutrients—I’m probably overdosing (lol).




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          2. Are you still with us here on the earth plane? :-) I’ve been buying Westsoy from our local Stop&Shop. Nothing in it but filtered water and whole organic soybeans. It’s delicious on my cooked whole grains (breakfast) with either honey or molasses, and etc.. I suppose I should get their fortified version (more calcium), but I’m a plain and simple type of gal. Don’t like a lot of additives, even the “good” ones. This has more protein, although I use only 1/2 cup.




            0
            1. Ha-ha—yeah I’m still here.

              I like soy milk mainly for the protein, and I’ve gotta put something on my hot cereal.

              I read T. Colin Campbell’s “Whole,” and what I took from it was to just eat a varied, whole foods, plant-based diet and don’t worry about it too much. Worry affects your digestion, sleep, et cetera, so it’s better just to celebrate the joy of a vegan lifestyle and be happy about it.




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        2. The Wyman’s of Maine are what I buy. Three pound bag for $8.99. I understand BJ’s has it for $7.99. I am considering cutting back a bit and going organic. I do love my BBs though. Less…we’ll see.




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        3. Soymilk gets bad press? My 68 y.o. physician father recently switched our family to Soymilk….just make sure you get the ‘lite’ variety…fewer calories….




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      2. The director of the Plants for Human Health Institute at NC State University says that the individually frozen berries have more active phytonutrients than the ones frozen in a blob. She also recommends very short thaws in the microwave–15 seconds or so, just to remove the frosting. “Microwave can be devastating if overdone,” she says.




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  2. I eat blueberries every day, at least 8 ounces. They are frozen, not organic (due to cost) and I sprinkle organic unsweetened cocoa (affordable) on these. I defrost for about 30 seconds in the microwave to soften them a little, not completely. I then eat them with chopsticks to slow me down. This is my favorite treat.




    0
            1. Yes, I’ve heard of eating with chopsticks…we Americans do wolf down our food, I’m as guilty as anyone. Went to a neighborhood potluck the other night for our Community Garden…host keeps chopsticks all around his kitchen for this very same reason..to help him and his family eat more mindfully…great inspiration, I must say!




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    1. hi steve, just letting you know that according to david suzuki, blueberries if not organic are on the ‘ dirty dozen ‘ list of food not to eat unless they are organic.




      0
      1. Sigh. I am aware of that. It is a compromise I make to my budget. Thanks for thinking of me☺ Maybe I will reevaluate our eat fewer blueberries?




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        1. Steve, I just wanna put in my 2 cents here. I used to make the same compormises for the same reasons. I’ll just give you an analogy to stir your thinking pot down to the muck: it’s like someone saying they’ll be hapy to eat poison food if they can eat more of it (more poison comes with). Try costco, or even 1/2 your daily, and save yourself the poison. It’s the same as the rational for taking pharm drugs, small help, BIG price = HARM. now that i just don’t eat anything that has poisons, if I have a bag of potato chips I feel the poison. being insensitive is not necesary condusive to health. . . PS> I also eat everything with chopsticx, including soup. ;))




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          1. Thanks Ruby. I will consider your kind suggestion. WRT microwaving, I’ve seen no evidence that this is unsafe to food. I don’t use plastic in a microwave and actually use very little plastic, period. Big fan of Mason jars Consider this video about cooking methods http://nutritionfacts.org/video/best-cooking-method/

            I don’t hover in front of the microwave so radiant energy is not a big concern. After pushing “start” I move about 5-6 feet away to do other tasks. Impatient? No doubt. :-)




            0
            1. steve, this thing crashed and lost 2 responses that had good info and . . .. i’ve been crashing for a week anytime i mention sub.versive info. the email i wrote you had the word t.esla. . . en.ergy tec.chnolo.gy. .and this started when I used thre word l.i.zrd. . . it’s a bit freaky .at least my email saves drafts. wanna chat off here for a jiff? rubifyitatgm




              0
            2. I find thawing my berries in a colander under cool to warm running water to thaw them works well and is quick. I have a tendency to overheat things in the microwave. :-)




              0
    2. Steve and do you notice anything? I have frozen ones in my freezer to and have access to frozen and since I am in tropic I do not see but mainland berries, so frozen is about all there is. Love to hear back.




      1
  3. I too have been eating frozen (thawed) blueberries every day, and have done so for many years. I mix them with grapes, chopped apple, and walnuts, and have them as part of my lunch. Delicious! They’re also good for breakfast when added to cooked steel-cut oats and other whole grains.

    (I don’t own a microwave oven.)




    0
    1. See the USDA database for the flavonoid content of selected foods and http://www.phenol-explorer.eu.

      Cranberries are the 15th best source of total anthocyanidins in the USDA database (~100 mg / 100 g), while cherries are the 30th best (~ 33 mg). The best sources are black raspberries (685 mg) and elderberries (485 mg). A convenient listing for those who haven’t entered all the USDA values into a spreadsheet is this sorted list of anthocyanin content at phenol-explorer. Anthocyanidins are the polyphenols, anthocyanins are an anthocyanidin with one or more sugars attached, as they’re usually found in foods.

      Note that anthocyanidins are not the only polyphenols of health interest. Strawberries have only moderate levels of anthocyanidins (less than cherries) but are the major dietary source of fisetin, which appears to punch above its weight in neuroprotetion.




      0
      1. Thanks for the link to the paper on fisetin, Darryl, very interesting. Unfortunately, there is still a distinct lack of literature on fisetin and the fisetin content of plant foods.

        Of the above mentioned potent sources for anthocyanidins, chokeberries are one of the most interesting, not only because of the high amount of cyanidin glycosides (regarding CD38 inhibition) but also because of their content of proanthocyanidins (~660 mg / 100 g FW), which is much higher than that of any berry (giving dried chokeberries roughly the same OPC content as cocoa powder).




        0
        1. There’s little to say about the fisetin content of plant foods: strawberries have 16 mg / 100 g, apples (with skin) have 3 mg / 100 g, and no other food has significant amounts. Japanese wax tree bark has significantly greater levels, and is the source for fisetin supplements.




          0
      2. Darryl, your second link above is about anthocyanin content of foods, which is spelled differently than the anthocyanidins Dr. Greger mentioned. Are these the same thing or is there a difference between them that matters?




        0
        1. There are only about a dozen anthocyanidins found in foods, which usually occur as part of one of 550+ anthocyanins, which differ from anthocyanidins by having one or more simple sugars or reduced sugars (aglycones) attached around the anthocyanidin backbone. The anthocyanin derivatives of a given anthocyanidin may vary in bioavailability and drug-like effects.

          The USDA database reports the anthocyanidin content of foods after their anthocyanins are hydrolyzed, so its more of an aggregate measure. The phenol-explorer site breaks down food contents further into the various anthocyanins.




          0
      3. Darryl,

        Any thoughts if we could expect the same cognitive benefits from the anthocyanins found in purple sweet potatoes as those found in blueberries? I can only find a rat study involving sweet potatoes and their effect on memory which was positive.

        Thanks




        0
        1. The anthocyanin content will differ, and as Phenol Explorer is down at the moment, I can’t say whether they’re comparable. Other sources indicate that purple sweet potato anthocyanidins consist of cyanidin or peonidin derivatives, whereas blueberry anthocyanins are a more complex mix of delphinidin, cyanidin, petunidin, peonidin, and malvidin derivatives. Without a human trial there’s no proof of comparable effectiveness, but we can speculate.

          Personally, I suspect anthocyanins are mostly absorbed as simpler colonic metabolites, so the actual anthocyanin profile may matter less than just consuming a bunch from whatever deep blue, purple, or black source. And while some of these compounds appear fairly promiscuous in their mechanisms, a common mechanism seems to be eliciting a hormetic effect to suppress chronic inflammation. Namely, even in small absorbed quantities they react to activate Nrf2 (a master regulator of antioxidant response), which in turn inhibits NF-κB (a master regulator of inflammatory/innate immune responses). Chronic inflammation is central to many diseases of aging, including cognitive impairment, so dialing it back a bit with any dark colored fruit, tubers or grains (cruciferous vegetables and tumeric are believed to work via the same mechanism) seems likely to offer comparable benefits.




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          1. Thanks a lot for the response, Darryl.

            I was most curious about purple sweet potatoes since I’m getting ready to help harvest some, namely the Okinawan variety as well as a couple others but what I was really try to get at was if making substitutions with a purple variety whether it be rice, cabbage, etc. could be a beneficial strategy to fight cognitive impairment so I appreciate your input.




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          2. Would you mind explaining Nrf2 pathways a bit more for us lay folks? How does Nrf2 regulate anti-oxidant response? Do other phytonutrients in addition to anthocyanins (or is it more correct to say “anthocyanidins”?) contribute to activating Nrf2? How does Nrf2 lead to inhibiting NF-kB? I’ve heard NF-kB described as the “black knight” of cancer cells because it helps cancer cells hide from the immune system. Does that make sense? As always, thanks for your insights, Darryl.




            0
            1. Individual cells, like whole bodies, maintain homeostasis throughout life, attempting to maintain an appropriate balance of temperature, acid/base, redox state, etc. Without the benefit of the wiring our technology might use, cells use chemical interactions, like negative feedback by products on the enzymes that shepard reactions along, or reactions with regulatory proteins that control gene transcription.

              Nrf2 (an abbreviation of “Nuclear factor (erythroid-derived 2)-like 2”) is one of these transcriptional regulators, and appears to play a paramount role in controlling endogenous antioxidant response to foreign chemicals, and has been extensively studied for two decades. When sulfhydryl reactive chemicals, like arsenic, cadmium or sulforophane from broccoli, curcumin from turmeric, oxidized anthocyanidins from berries, EGCG from tea, etc. enter cells, Nrf2 is released into the cell nucleus, where it attaches to DNA upstream of several hundred genes important in cellular protection (glutathione synthesis, antioxidant enzymes, DNA repair, protein chaperones, metal chelators, and toxin export), and promotes their transcription. I’ve discussed Nrf2 in more detail in some past comments: a, b, c, d, e, f.

              NF-κB is a master transcriptional regulator of cellular inflammatory signalling, and has an antagonistic role to Nrf2. Just as Nrf2 activation inhibits NF-κB, NF-κB activation inhibits Nrf2. This makes sense for cells, much of the generation of reactive chemical species is due to inflammatory responses, for example from NADPH oxidases regulated by NF-κB. By enlisting Nrf2’s detection of excess redox stress, cells have a feedback mechanism for regulating inflammatory production of radicals and protecting themselves. You’ll note considerable overlap between the list of Nrf2 activators I assembled and lists of NF-κB inhibitors (eg, Table 1 here), so much so that I suspect the well understood mechanism for Nrf2 activation, and its known inhibition of NF-κB, likely mediate the connection.




              0
              1. Thank you, Darryl. Is the following a correct description of the positive feedback loop discussed in one of those articles you cite?

                Oxidative stress activates NF-kB—
                and NF-kB causes NADPH oxidase to be produced (which is what exactly?) –
                and NADPH oxidase activates ROS.

                So is this how oxidation and inflammation are intertwined?




                0
                1. It an important but not the only way oxidative stress and inflammation are intertwined. I occasionally come across images like this:

                  http://www.nature.com/nrneph/journal/v2/n10/images/ncpneph0283-f1.jpg

                  The body regularly uses low concentrations of the less harmful radicals like nitric oxide and hydrogen peroxide for intra- and inter cellular signalling, and also generates copious superoxide to deal with perceived infections. There are positive feedback cascades by which this signalling can be amplified (like the squeal when microphones are pointed at speakers). Enough nitric oxide and superoxide in one place, and the very destructive radical peroxynitrite is formed. One paper that address this pathological cycle in atherosclerosis is:

                  Zinkevich & Gutterman 2011. ROS-induced ROS release in vascular biology: redox-redox signaling.

                  Some of these positive feedbacks occur at mitochondria and membrane bound enzymes and don’t require NF-κB, but many of the longer term inflammatory responses that require gene trascription do. When scientists talk about inflammation, they ‘re usually talking about increased levels of the signalling cytokines like the IL-1s, TNFα, or IFNγ, but these aren’t intrinsically toxic, its the radicals that are generated downstream that do the dirty work. The body tries to keep this regulated, sometimes with anti-inflammatory cytokines like IL-10, and likely also with Nrf2 mediated antioxidant response.

                  Much of the benefit of whole plant based diets appears to be in interfering with feedback cycles of inflammation and oxidative stress. by reducing initial innate immune alarums (set off by saturated fats, endotoxins, Neu5gc, etc), by directly quenching excess radicals (with direct antioxidants like vitamins C, E, the carotenoids, ergothioneine, and folate), by making less inflammatory hormones (with less arachidonic acid and more omega-3s), and in the case of many phytochemicals, by activating Nrf2 mediated endogenous antioxidant response and directly or indirectly interfering with NF-κB promoted inflammatory gene transcription.




                  0
                    1. Neu5gc has its own topic category on NutritionFacts, and perhaps a recent damning study will feature in a future video. I believe I erred in describing it as a stimulator of innate immune response, as its a red meat derived sugar that’s incorporated into our cell membranes and recognized as foreign by our adaptive immune response. There’s speculation that Neu5gc is involved in nonresolving inflammation.

                      Stimulants of innate immune response are generally pathogen fragments, and activate subvarieties of Toll like receptor. They include peptidoglycan (TLR1) or lipoteichoic acid (TLR2) from Gram positive bacteria, double stranded viral RNA (TLR3), bacterial lipopolysaccharide (endotoxin) (TLR4) from Gram negative bacteria, bacterial flagelin (TLR5), single-stranded viral RNA in endosomes (TLR7), guanidine rich DNA (TLR8), unmethylated CpG DNA (TLR 9) etc. Some of these receptors are critical to chronic inflammatory disease, for example mutant mice lacking TLR4 don’t develop atherosclerosis and insulin resistance when fed the same high fat diets that induce these in wild-type mice. Saturated fats are believed by some to also active TLR4, both by increasing intestinal permeability to endotoxin, and perhaps also directly by causing TLR subunits to raft together. There’s even been evolutionary biology speculation on just why our innate immune responses should respond to dietary saturated fats. EDIT FORTHCOMING WHEN I FIND THAT PAPER.




                      0
                    1. That’s from Vaziri, N. D., & Rodríguez-Iturbe, B. (2006). Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension. Nature Clinical Practice Nephrology, 2(10), 582-593.

                      No, I don’t spend my idle hours looking at kidney journals, it just happened to be a simple diagram found in Google image search that illustrated how the amplification circuits for inflammation could result in runaway oxidative stress, but which is consistent with other more jargon / pathway specific ones.




                      0
                    2. Thanks. No rush. I’m also wondering whether this cycle of oxidative stress and inflammation is involved in the actual initiation of cancer? It would clearly be relevant to promotion and spread of cancer, right? Can it actually cause damage to DNA–or perhaps keep DNA from repairing itself? I realize some scientists (Thomas Seyfried, for example) suggest cancer is caused by damage to the mitochondria of cells–and an out of control feedback loop of ROS and inflammation would likely fuel that, correct? I’m guessing here and welcome your expertise.




                      0
                    3. You could do worse than reviewing Reuter et al 2010. Oxidative stress, inflammation, and cancer: How are they linked?. Where this review fails IMO is the assertion that ordinary aerobic respiration is the major source of oxidative stress, which is contested, and not focusing on the amplification cycles for ROS and inflammation noted above.

                      If mitochondrial respiration is just a fractional contributor to oxidative stress, then much more blame can be attributed the alternative major sources noted in the second link, peroxisomes (involved in oxidative toxicity from burning C14+ saturated fats) and NADPH oxidases (superoxide generating enzymes involved in inflammation and implicated in both cancer initiation and progression/survival).




                      0
                    4. Could you tell us about TLRs 7 and 8? My son was prescribed (overprescribed–He took it for much longer than the FDA approves it for–iatrogenic error) a medication that works by binding to TLRs 7 and 8, thus activating several pro-inflammatory cytokines and has been experiencing neurological problems (dizziness, brain fog, dyslexia, which he never had before). So far, we’ve had no luck with medical specialists. Any thoughts on how to reverse the inflammatory signalling?




                      0
              2. Thanks so much for this. You have surely put a lot of work into distilling all the information out there, and your fans in cyberspace are very appreciative.

                Re: your list of Nrf2 inducers:

                1/ So are you saying that the strongest Nrf2 inducers are also the strongest NF-kB inhibitors? Have you compiled a similar list of the strongest NF-kB inhibitors?

                2/ It’s interesting that coffee and black tea, according to your list, are stronger at inducing Nrf2 than green tea, with its EGCGs. Comments?

                3/ What’s the deal with luteolin? I see that at the bottom of the list, you’re questioning its actions. And how might Nrf2 inhibitors help if you’re taking chemo?




                0
  4. Very good info. – confirming previous videos, esp the one about adding Pepper and Cardamom to blueberries for maximum effect – I can feel this healing me big time!! I recommend it to all! I sometimes use Young Living essential oils cardamom and black pepper – this is even more potent than the ground spices.
    http://nutritionfacts.org/video/boosting-natural-killer-cell-activity/

    However, I would not go the grape juice route mentioned in the video – to get my berries. Ever since I read a theorem presented by Dr. Mercola (below) I stay away from canned or bottled fruits and juices. (Unless you juice them and eat them – right away.)

    WE ALL KNOW HOW EXTREMELY TOXIC FORMALDEHYDE IS (let alone methanol) – IT’S USED TO EMBALM PEOPLE!

    http://articles.mercola.com/sites/articles/archive/2010/09/14/why-do-heavy-drinkers-outlive-nondrinkers.aspx
    Mercola – “New Concern in Your Food: Wood Alcohol (Methanol)

    Fresh fruits and vegetables contain small amounts of
    naturally-occurring methanol, and the artificial sweetener aspartame
    converts into methanol in your body.

    Normally this is not a problem as the methanol is typically bound to
    pectin, and since your body has no enzyme to metabolize that bond it is
    simply excreted in your stool and none of the methanol is absorbed into
    your body.

    However, the problem occurs when you can or bottle fruit- or
    vegetable juice, as the methanol tends to then dissociate from the
    pectin into free methanol, which you do absorb.

    The methanol you absorb readily passes the blood brain barrier where
    it can be converted to form formaldehyde, which is a potent toxin that
    actually causes most of the damage.”




    0
    1. Dr Mercola says consuming saturated fat and cholesterol is not a problem, so I take whatever he says with a grain of salt. If what he claims about commercial juices were such a horrific danger, I’m sure Dr Greger would have a video about it by now.

      The real problem with commercial juices is the missing nutrients found in the whole foods the juices come from and the extreme ease of calorie over consumption of such calorie-dense liquids.




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  5. Doctor G!! Do you think that since the whole berry is REQUIRED to see significant aid to brain function, that this might have some bearing on why coconut oil and procesed flakes may not show positive results but . . . that perhaps brains and nerves might show some significant help from the oils in coconut if coconut were consumed whole, and fresh??????? . . . Since no studies have been done with whole fresh coconut, and with my neurological disease I have greatly significant benefit in nerves and calmness and I think mental aquity as well because of it, yet prefer not to consume the oild internally and do not have the same affinity for even the flakes, might this idea not have some merit, to at least leand to consideration? Also I wanted to say, that 3 days is as long as a fresh coco will last in the fridge, and when they go bad it smells HORRID, so the oils are as volital and krill, which loses 50>75% of it’s potency before it reaches shore! Anywho, I’d love if some consideration of this idea that this saturated fat, from the fresh coconut, might be the thing missing in brain and nerve health beyond anything that’s thus far been measured. I think someone should push for a study. Alzheimers is HUGE in this country, as are other neurological and nerve related disorders.




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  6. Gee Wilikers, 2 years for a typical life span of 75 years is 2.7%. I won’t even walk across the street for a sale of only 2.7% off. Why bother?

    Speaking of another wasted effort — why bring up the problem of oxalates in cinnamon without telling the rest of the story which would be every Meat Eater’s excuse to keep on.




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    1. “2 years for a typical life span of 75 years is 2.7%. I won’t even walk across the street for a sale of only 2.7% off. Why bother? ”
      The POINT being that IF you do many and various things like this to improve your health…you MIGHT end up gaining 27%? And avoid the miseries of a slow death in old age? Your choice as always.




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    2. Drezzle: Your analogy only works if you place the same value on a couple of bucks that you place on two years of healthy brain life. I personally place a very high value on my brain health, as do many other people. If you don’t, of course, that is your prerogative. But hopefully you can see why others would find this information to be extremely valuable. And what is the price to get this high return? Eating some blueberries? Oh, the pain… (You see the point.)




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  7. Calling attention to an important paper:

    Levine, Morgan E. et al. “Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population.” Cell Metabolism 19 (2014): 407–417.

    Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages.




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    1. I think this is a critically important paper, providing the best corroboration yet for the conclusions of The China Study. But Darryl, since I know you would have read the article, what is your comment on Figs J and K in the mouse study part of this paper – soy just as powerful in raising IGF-1. Perhaps this is a mechanism for why, in the human study, the control for animal protein only reduced, but did not eliminate the elevated risk associated with moderate and high protein diets? That is a little worrying for those of us who eat soy.

      It is interesting that the next paper in the journal by entirely different authors, a study in about 900 mice, reaches pretty much the same conclusion (the mice on the low protein diets lived longest).




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      1. Kate: In that study you are referencing, do you know if they were using whole soy or traditional soy products (like tofu) – or if they were looking at soy protein isolates?

        It is my understanding that it is the soy protein isolates that cause a problem and understandably so. But I would be interested in knowing if there is a study showing issues with whole soy consumption. (Then again, we are just talking mice…)




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        1. No I don’t know, but since they were feeding it to mice, I doubt they were using organic tofu! They were comparing casein and soy, and both raised IGF-1 equally, and lowered one of the IGF-1 binding proteins equally. I know that other studies have found soy raises IGF-1 and I am not aware that this effect depends on the type of soy – I don’t know that for sure, but I doubt if that is the case because it wouldn’t really make sense biologically. Soy raises IGF-1 because it has a similar amino acid profile to animal proteins (presumably). That is perhaps good and bad.




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          1. Kate: based on your description, it *sounds* to me like they were using soy protein isolate. This means that they just pulled out the protein pieces of soy. That is like pulling the oil out of olives or looking at the health benefits (or lack there of) of white flour and then declaring that olives and wheat are bad for you/cause harm.

            In other words, if they were using soy protein isolates, then I think the most you could conclude from those studies is that humans should stay away from the type of junk/packaged food which contains soy protein isolates. I think this conclusion is valid, because we have good evidence that traditional soy products are protective against cancer in humans. So, I don’t think you could look at a study that uses soy protein isolates on mice and conclude that humans eating “whole” or traditional soy products raise IGF-1 in a way that is unhealthy.

            That’s just my thought. Thanks for your reply/clarification.




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            1. Thea – there is so much more to this study than the tiny bit I mentioned about the soy/casein comparison. It is a pretty compelling study (series of studies actually) – I would highly recommend that you and other regular contributors to this site read it. It is freely available – Darryl has posted the link above.




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                1. Soy is a pretty complete protein. I would expect soy protein – in whatever form – to have effects quite similar to casein, because of its similar amino acid profile.




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      2. Soy is fed to livestock because it is a cheap, relatively “complete” protein that stimulates growth. The same is true in humans, and between the ages of 20 and 65, the harms of excess growth signalling may outweigh the benefits for many.

        Dr. Greger addressed these issues in what I consider his best thematic series of videos to date, from 2012:

        IGF-1 as One-Stop Cancer Shop
        Cancer-Proofing Mutation
        The Answer to the Pritikin Puzzle
        Protein Intake & IGF-1 Production
        Higher Quality May Mean Higher Risk
        Animalistic Plant Proteins
        Too Much Soy May Neutralize Benefits
        How Much Soy Is Too Much?
        Plant-Based Bodybuilding

        Soy has many good things going for it that may reduce cancer risk. Whole soybeans are high in fiber. The isoflavone phytoestrogens preferentially stimulate estrogen receptor β, with protective effects against breast and prostate cancer. These two benefits may not apply to soy protein isolates. Soy protein has the highest ratio of lysine (the limiting one in vegan diets) to leucine (a branched chain amino acid that is the most effective IGF-1 stimulator), which means one can achieve adequate protein with less growth stimulation with soy than with other plant proteins.

        So the issue comes down to how much food chosen for high protein (soy, nuts etc) is really necessary for health, and my readings suggest the answer, for those between 20-65, is some, but not much. Protein is in all whole foods, and protein deficiency is exceptionally rare unless one is young and eating a diet wholly comprised of very low protein foods like taro and cassava.




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    2. From your link: “These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity.”

      I’m wondering what kind of “high protein” they’re talkin’. Red meat, etc.?.




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      1. Their three dietary cohorts were low protein ( 20 % of calories). It should be noted that few Americans would fall into the low protein category (~ 1% of the population), while only about 7-8% of the population would fall into their high protein category.

        The study did not differentiate further than plant protein and animal protein. There are also confounders like saturated fat that arguably weren’t well controlled for. However, this study adds to a body of evidence about the long-term harms of high protein, and especially high animal protein, diets. A sampling:

        Low-carbohydrate–high-protein diet and long-term survival in a general population cohort (2006)
        Low carbohydrate–high protein diet and mortality in a cohort of Swedish women (2007)
        Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort Studies (2010)
        Dietary correlates of plasma IGF-1 and IGFBP-3 concentrations (2002)
        Association of diet with serum insulin-like growth factor I in middle-aged and elderly men (2005)
        The association between diet and serum concentrations of IGF-1, IGFBP-1, IGFBP-2, and IGFBP-3 in EPIC (2009)
        Insulin and insulin-like growth factor signalling in neoplasia (2008)
        The insulin and insulin-like growth factor receptor family in neoplasia: an update (2012)




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  8. Hi Dr. Greger,

    How many ounces or cups of blueberries should be consumed each day to receive the benefits outlined in your video?

    Just trying to get a better sense of magnitude: 3 cups? 1 cup? Half a cup?

    Thank you!




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    1. In the cognitive decline paper, high intake was at least one serving per week. Given a serving is only 1/2 cup, the paper indicates those in the category eating at over Tbsp a day had significant brain benefits. More may be better, but this study didn’t say.




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      1. Yep, cranberries. My freezer is full of cranberry boxes. The only problem is that I have to use a blender and mix it with other fruits – mostly sweet berries – to make them palatable.




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      2. I wonder how that “contest” would have looked liked if it actually included berries high in OPC and/or anthocyanins, like those I mentioned above. Cranberries have the highest amount of anthocyanins among the contenters, but chokeberries or elderberries provide fifty times(!) as much.




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    1. You can go to http://www.phenol-explorer.org and see foods listed by their anthocyanin content, it is a bit difficult to navigate, though.

      If you just want the “Top 5”, the graph below shows the berries with the highest anthocyanin content. Blue bars are anthocyanins, white bars are OPC. Aronia, also known as black chokeberry, contains about ten times(!) as much anthocyanins as commercial highbush blueberries. “Holunderbeeren” is elderberries, providing as much anthocyanins as aronia, but much less OPC (and they can only be eaten after being heated). Third is black currants, fourth wild blueberries (or bilberries) and fifth European cranberries (or lingonberries). To put this into perspective, commercial blueberries provide only about 150 mg anthocyanins, and cranberries 30 mg. Even the much hyped açaí berries contain only about 300 mg – one fifth of what is found in aronia or elderberries.




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      1. Thank you for your post, it’s very informative. I believe the correct link is http://www.phenol-explorer.eu and you’re right, it’s a bit confusing to browse . The anthocyanin and OPC levels you mention are for fresh or dried Aronia berries? I found dried Aronia berries online.




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        1. Yes, it’s .eu, I confused the top level domain, sorry.

          The levels (1480 mg per 100 gr) are actually for fresh Aronia berries. Dried berries are approximately 1/10th of the fresh weight, but you loose a small amount (~10%) of anthocyanins during drying. I would expect dried Aronia berries to have more than 100 mg of anthocyanins per gram. Thus a single teaspoon (5 gr) should provide about as much anthocyanins as a pound of blueberries.




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  9. If someone goes on a Candida cleanse for three months, is vegan, how does that person get enough protein without compromising their diet?




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  10. question. I was adding blueberries to my smoothy in the morning. However, my blood sugar went up too much with blueberries added. (otherwise have done only veggies). got any ideas?




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    1. Some of the anthocyanins that the Dr. is talking about can also be found in purple cabbage and black and purple Thai rice. I’m thinking that both of those would have a slower glucose uptake. Both of those would obviously have unique sets of other cyanic-phytonutrients that may not have brain saving properties but they are both worth adding to your diet anyway. I’ve added both because blueberries are too expensive at some times of the year here. If you want to keep the blueberries in your smoothies try adding ground flaxseed and chia seeds or hemp seeds. (if you aren’t trying to cut out lipids, as these seeds both have their share. Good lipids but lipids not the less.) 5 months after you asked but there you go.




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  11. BLUEBERRY SEASON HARVESTING GUIDE

    * NOTE– The following is my personal blueberry season guide, but my guide may not match your own location and conditions. In all cases, interpret and apply what you read carefully and safely to your own situation. Better still, write your own manual as you determine what works for you and your family.

    —————————–

    Depending on where you live, blueberries are abundant on local US farms from late May through the first of August, and more briefly and later in the year for higher latitudes. The cost you can expect per pound is about half of the lowest grocery price at peak season. The remaining cost to you is fewer than two hours of total travel time (to and from), and fewer than two hours picking berries from the bushes.

    On your blueberry expedition, wear a long-sleeved shirt or blouse to protect arms from scratching, and always comfortable, casual cotton clothing. Choose a gardening shirt or blouse dedicated to dirty garden work, since reaching into blueberry bushes will stain garments more or less permanently. Be sure to wear a hat and sunscreen because of the bright sun directly overhead, and on even a hazy, overcast day, some overexposure is possible. In all cases, keep about a quart of drinking water near– even under a hat, the hot sun dehydrates very quickly and sunstroke can be even fatal.

    Insect repellent is optional, depending on whether mosquitoes are prevalent, but do not apply any lotion or sunscreen with fragrance because it may attract the occasional bee or wasp. Those subject to risk because of insect stings should make sure to bring their epinephrine injector against anaphylactic shock.

    Most important of all, wear sunglasses (wrap-around or landscaper’s sunglasses) to protect the eyes against blueberry bush branches. A branch can scratch a cornea easily in a single second when the branch simply brushes across a cheek.

    Blueberries cost about $1.50 pound on local berry farms, so each brimming, 6.5-pound bucket of berries costs about $9.75 per bucket. By freezer volume and weight, each bucket translates to approximately four bulging quart resealable bags of 1.625 pounds each.

    Most individuals can pick two buckets easily in two hours, which represents 13 pounds, or a total of $19.50 at the farmer’s pay counter and scale. Ambitious families (which can keep children from eating too many of the berries) can harvest perhaps four buckets (or more) in two hours, but it takes a disciplined effort. A person can stay all day in the blueberry field, if desired, but most people (especially children) have had enough after two hours. It always helps if a farm has public restrooms available, but make sure to accompany the children for safety.

    The reward of all this enterprise is putting the berries away in the freezer as quickly as possible, to preserve their delicate flavor. Berries which remain in their farm-distributed plastic bags ferment quickly and not only lose flavor, but gain a strange, somewhat off-flavor from the early action of native yeast spores on the surface of each berry.

    The easiest processing method is to bag the berries immediately, and wash the berries only later, before eating. However, berries also can be washed quickly before freezing, if desired.

    For protection against bird- and insect-borne disease, my preference is to rinse the incoming berries before freezing with a very diluted solution (one tablespoon per gallon) of household bleach in a two-gallon bucket of water, pour in berries, and swirl the entire mixture continuously for about 120 seconds. This precaution also kills the yeast on the skin of each blueberry to protect against further fermentation while chilling, and a light solution of bleach is seldom detectable. In all cases, let your own nose be your guide about the amount of bleach to use, and dilute accordingly since some bleach products are at a stronger concentration. When mixing and adding bleach, it is a good idea to wear protective eyewear of some description as protection against splash-back.

    If an immediate bleach-solution rinse before bagging and freezing is the chosen course, berries (at option) can be rinsed in a second bucket of clean water, and drained quickly. They need not be completely dry before bagging– simply drain each quart freezer bag of excess water before sealing the bag. Drying the berries on old towels placed on the kitchen floor under a box fan can be done, but is not essential and risks fermentation.

    The natural oil on some blueberry varieties which gives it a dull finish prevents newly-harvested berries from sticking together when placed in the freezer. This oil usually will not be removed by a brief rinse in water, or even a light bleach solution.

    With frozen berries, avoid thawing and then refreezing, since they will lose flavor and become mushy. If utility power fails while in storage, the typical home freezer should protect the berries for at least 24 hours if the freezer is not opened. If transported to another location, the berries can be placed with ice in an insulated cooler / ice chest to avoid thawing, with a layer of aluminum foil or even newspaper over the top to keep the berries frozen longer.




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