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Are Berries the New Snake Oil?

I have nothing against berries. I, in fact, enjoy many kinds of berries in my diet. My favorite fruit, the banana, is actually a berry (botanically speaking). I am disturbed, however, at the extent to which various kinds of berries are being sold as the latest superfood cure-all.

Dr. Oz, for example, has been pushing the lingonberry (a relative of the cranberry and blueberry) as “a new superfruit for longevity.” An attached article on his site states:

“Today, scientists are showing its value in both human and animal studies that are proving to have positive results.”

Curiously, there are no links or references to these studies.

Polyphenols and Antioxidants

We are still in the midst of the “antioxidant craze” – if you read the justification for just about any so-called “superfood” or longevity supplement you are sure to read about antioxidants. I have already covered antioxidants, but briefly: Cell metabolism in part creates oxygen free radicals which are molecules that steal electrons from other molecules, causing a cascade of reactions that can damage proteins and other chemicals in the body. Anti-oxidants are chemicals that can stop free radicals and limit the damage. They therefore decrease “oxidative stress” on cells. So far it sounds like anti-oxidants are therefore a good thing and we should be gobbling up as much as we can. However – free radicals and anti-oxidants exist in cells in a homeostasis. Free radicals are used by the immune system, for example, to fight invading organisms. They are also important signaling molecules, triggering other cell-protective mechanisms.

Therefore, taking large amounts of anti-oxidants and disrupting this normal balance  may not necessarily be a good thing. I’m not saying it’s necessarily a bad thing, we just don’t know. You cannot extrapolate from pre-clinical data – essentially looking at what happens to various molecules and cell functions – to clinical claims. The role of free radicals and anti-oxidants in the body is too complex for us to extrapolate to net clinical effects. At best the existing data might suggest the potential for a clinical effect, but in order to know we would have to do properly designed clinical studies.

A researcher observed in a recent article:

“Antioxidant therapies have been evaluated in placebo-controlled trials involving tens of thousands of patients. Despite pathophysiologic, epidemiologic, and mechanistic data suggesting otherwise, these clinical trial results have been, to date, mostly negative in the setting of chronic preventative therapy.”

He goes on to speculate that perhaps we have not used the right antioxidants, in high enough dose, for long enough a period of time (the usual special pleading heard after negative trials.) Or – perhaps they just don’t work. Perhaps pathophysiologic, epidemiologic, and mechanistic data can be misleading. At best they can provide plausibility and prior probability, but in the end we need rigorous clinical trials.

This is because one tiny fact of metabolism that we might be missing can undo all the pathophysiological plausibility of hundreds of studies. The history of modern scientific medicine is festooned with a massive trash heap of therapies that were highly plausible in animal and in-vitro studies, but failed in rigorous clinical trials. This history should be humbling. It should motivate the intellectually honest doctor or scientist to avoid making grandiose claims such as increased longevity or disease prevention because of interesting preclinical data.

Polyphenols seem poised to be the next anti-oxidants. Berries have polyphenols (which themselves are antioxidants) and other antioxidants, which is partly why there is a stream of superberries hitting the health food market. Oz, for example, touts the health benefits of berries and cites cranberries for urinary tract infections as an example. It is true that cranberries likely have some benefit in preventing UTI, but the clinical studies have been problematic. A recent review concludes:

Meta-analyses have established that recurrence rates over 1 year are reduced approximately 35% in young to middle-aged women. The efficacy of cranberry in other groups (i.e. elderly, paediatric patients, those with neurogenic bladder, those with chronic indwelling urinary catheters) is questionable. Withdrawal rates have been quite high (up to 55%), suggesting that these products may not be acceptable over long periods. Adverse events include gastrointestinal intolerance, weight gain (due to the excessive calorie load) and drug-cranberry interactions (due to the inhibitory effect of flavonoids on cytochrome P450-mediated drug metabolism). The findings of the Cochrane Collaboration support the potential use of cranberry products in the prophylaxis of recurrent UTIs in young and middle-aged women. However, in light of the heterogeneity of clinical study designs and the lack of consensus regarding the dosage regimen and formulation to use, cranberry products cannot be recommended for the prophylaxis of recurrent UTIs at this time.

So perhaps there is some benefit in young to middle-aged women, but not other groups. But there is a suggestion that most people cannot maintain the diet for long. Further, taking regular high doses may cause interactions with prescription drugs (I didn’t see that on Oz’s website). In the end, the utility of cranberries for UTI prevention is questionable and problematic. Even if there is an effect, there are problems with compliance, side effects, and dosage.

This, of course, brings up a generic point about so-called nutriceuticals – foods as drugs. It’s difficult to regulate bioavailability, dose, and other factors when food is the drug delivery system. Further, there may be unintended consequences of altering the diet in order to maximize certain nutrients. Berries, for example, are high in calories and sugar.

The flavonoids mentioned in the review above, that can cause interactions with drugs, are a class of polyphenols. They have other potentially negative effects, such as impairment of glucose metabolism. The combination of high calorie, high sugar, and impaired glucose metabolism is not a good one, especially for diabetics. The net clinical effect of this has also not been studied adequately, but it’s just as plausible as any alleged beneficial effect.

Conclusion

Metabolism and biology are complex. That may seem like an obvious statement, but it bears repeating. In the US and many other countries there is little to no regulation of food and supplement health claims. In the US we have DSHEA, which allows for companies to make health claims without any burden of proof as long as they don’t claim to treat or cure specific diseases. We therefore have a health food and supplement industry that aggressively markets a never-ending sequence of new products with amazing health claims (either direct or implied). Some of this is simply made up, but much of it is extrapolated from basic science – which gives it the marketing appeal of sounding as if it is supported by scientific evidence. The problem is magnified when celebrity doctors, like Oz, promote these products without providing the background information to put them into the proper perspective.

Chances are most of these products are simply useless, but some may even be harmful. In most cases we lack rigorous clinical trials to understand what the net clinical effects of specific products, foods, and diets in specific populations actually are. In the last couple of decades we have seen the rise of noni-juice, acai berry, pomegranate products, blueberries, now lingonberries, and others – all with amazing claims and a simplistic and over-hyped narrative that is not supported by the science. That is the very definition of snake oil.

Posted in: Herbs & Supplements

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33 thoughts on “Are Berries the New Snake Oil?

  1. tgobbi says:

    Dr. Novella: “Curiously, there are no links or references to these studies.”

    Hmm, one wonders why that may be… Perhaps they don’t exist? No, it’s too cynical on my part to even think such a thing. I know! Dr. Oz must assume that his word is good enough and that there’s no need to corroborate his claims. Yeah, that’s it: the inerrant word of the woo deity.

  2. Janet Camp says:

    What is wrong with Oz, anyway? He has to know he has crossed the line. Much as I like lingonberry jam on a lovely Swedish pancake, I seldom indulge in something that is basically dessert. I think lingonberries, like cranberries are pretty much unpalatable without a lot of sugar. Perhaps that is why the juices are so popular, although in the case of cranberry at least, they are also significantly sweetened.

    I eat lots of berries (the sweet ones, straw, rasp, black)–off the vine and on my oatmeal, no sugar. Love ‘em. But I eat lots of kale as well, so I guess I’m a food geek. How do I make a zillion dollars from this?

  3. Exilapotekare says:

    Within the European Union the legislation is somewhat different – here any health claim for a food/supplement now needs to be approved by EFSA/the Commission. This is just being implemented, but thus far the antioxidants have had a hard time getting approval since it is based on an “evaluation of the scientific evidence”. At the moment only eight supplements can be sold with the health claim of “protection against oxidative stress”: vitamins B2, C and E, the minerals copper, manganese, selenium and zink, and olive oil polyphenols. Not a single berry in sight…

  4. weing says:

    @Janet Camp,

    Actually the strawberry is not a berry but an aggregate accessory fruit.

  5. cervantes says:

    Oz should go over the rainbow — he is a bigger fraud than the Great and Powerful Wizard of that fabled land.

  6. tgobbi says:

    Janet Camp: “What is wrong with Oz, anyway?”

    The answer is simple: $$$$$!

  7. mousethatroared says:

    Janet Camp”I eat lots of berries (the sweet ones, straw, rasp, black)–off the vine and on my oatmeal, no sugar. Love ‘em. But I eat lots of kale as well, so I guess I’m a food geek. How do I make a zillion dollars from this?”

    Food Critc? Recipe Blog? Fresh Food Catering? Oh, Oh, maybe you could start a fresh fruit and vegtable competitive eating festival. The vegans are really left out of the competitive eating ring at this point….an untapped market.

  8. Jeff says:

    Apparently Dr. Oz can’t be bothered to provide references, but such studies do exist:
    http://www.sciencedaily.com/releases/2012/03/120307145825.htm

    One way to avoid the calories and sugar is to consume berry extracts. Maybe these extracts could protect our brains from radiation exposure:
    http://www.ncbi.nlm.nih.gov/pubmed/16837106

  9. RD says:

    Thank you for the article. It is a breathe of fresh air exposing some of these beliefs. I tell my patients to eat the whole food vs trying to get the nutrients from supplements. In this case, berries, not only does a person consume the antioxidents, but also other vitamins, minerals, fiber and other phytochemicals that aid in a person’s health. Consuming a cup of raspberries has only 64 calories and 5g of sugar vs 1 cup of ice cream can have close to 300 calories and 28g of sugar (depending on the brand). For a sweet treat, berries are great. Once the food is processed into juices or dried fruit, because of the change in volume, the calories go up. I encourage pts to eat the rainbow of colors, to consume a variety of these additional nutrients. Sounds too easy right? I try to explain that the body is very complex and it is impossible for just one food or food group to provide everything our body needs. I encourage them to eat as many fruits and vegetables as possible throughout the day. Since some of the nutrients, our bodies are not efficient at absorbing, one high dose of it does not necessarily mean we are abosrbing it all, in fact often not.

  10. Just because I cannot resist:

    Despite the name, the Acai berry is not a actual botanical berry, but a botanical drupe.

    An other commentator label strawberries, raspberries and blackberries as berries (no doubt meaning culinary berries), but neither are actual botanical berries. Strawberries are aggregated accessory fruits, raspberries and blackberries are small aggregated drupes (drupelets).

  11. DevoutCatalyst says:

    Guess that makes you a tardily dehiscent turgid woody pod.

  12. Jan Willem Nienhuys says:

    I have a question. How do all these things get into the cells of the body? Cells have a cell membrane that doesn’t just let anything through. Presumably some molecules are admitted and other molecules / ions are pushed out. I once read that for example cancer medicines only can act if they get into the cancer cells, and if the cancer cell somehow prevents them entering, then they don’t work.

    Maybe this is all explained in biochemistry 1 but I never took that course. So: if someone eats lots of antioxidants, how can s/he known that they will be taken up by the cells, rather than broken down in the liver? Do they ever get out of the digestive tract?

  13. Angora Rabbit says:

    @RD – you’ve said it right. At least these people will be eating more fruit instead of junk food and getting the benefits of the fiber and nutrients, also displacing bad foods. The downside are the food/supplement companies attempts to monetize this by making extracts and derivatives that add expensive junk back to the diet without the health benefits from the whole food. At least the berries are grown here instead of being The Next Tropical Food that Will Save Us (while deforesting and taking food away from the native populations).

    Steve, you missed the cranberry and cherry crazes. :) (Sorry I am writing from cranberry mecca where we even have named cranberry professorships.)

    Thanks for pointing out that it’s a moving target, kinda like the Pope and evolution. First they touted supplemental intakes of antioxidants like b-carotene. When those actually increased cancer risk (see the CARET study) they shifted to vitamin E. When that didn’t add health benefits above the DRI, they shifted to other carotenoids like lycopene. Ditto failure. Now it’s the jump to flavinoids and polyphenolics. Same story, fifth verse. You’d think they’d twig to it by now.

    At the day’s end, there is no magic bullet. Dump the processed food. Eat whole foods. Learn to cook. We’d do so much better than by jumping on the next NutriFashionista bandwagon.

  14. Angora Rabbit says:

    @JWN: yes, there are broad transporters for these compounds in the jejunum and illeum, as well as the liver. They can enter the bloodstream, often bound with albumen or lipoproteins, and can enter cells such as per ABC transporters or lipid transports, which have broad specificities. The downside is that one of the liver’s major jobs is to dispose of these via the bile, less often the kidney, so it can actually be quite difficult to achieve pharmacologically relevant blood levels thanks to the enterohepatic circulation and first-pass effect.

    The problem I usually encounter in these studies is that the authors don’t waste time with the actual pharmacokinetics. Doubtless because it would demolish a beautiful sales / patent opportunity. They throw the stuff on cell cultures and then start marketing their claim, without even back-of-the-envelope calculations to figure out how much one would have to eat. There’s often a complete absence of bioavailability data, let alone knowing what the actual relevant compound is within the mashed up extract that’s being tested.

  15. daedalus2u says:

    The importance of reactive oxygen species (ROS) in cell signaling cannot be over emphasized. Many of the most fundamental processes in cells are regulated by ROS, including ATP generation in mitochondria and synthesis of membrane components and hormones by P450 enzymes.

    Various ROS compounds are used as signaling compounds, that is they are generated at a site, diffuse a distance and activate a sensor which triggers downstream signaling cascades. These sensors can only sense the sum of signals from all sources, including the background. The background level of ROS is an important component of the signaling pathways.

    You can’t just whack at ROS physiology with supraphysiological levels of antioxidants and expect things to work better. That isn’t how physiology works.

    There are no large, well done, long term, placebo controlled, double blinded studies that show health benefits of anti-oxidant supplements.

    I challenge anyone to find any. Last I looked there were none.

    There very likely are no health benefits, short of actual deficiencies.

  16. Always Curious says:

    Jeff,

    The science daily article references a paper: http://pubs.acs.org/doi/full/10.1021/jf2036033 in Journal of Agriculture & Food Chemistry. It has a very long list of impressive cell culture experiments, but the human studies were very preliminary. For example, I noticed that http://www.ncbi.nlm.nih.gov/pubmed/10822287?dopt=Abstract and http://www.ncbi.nlm.nih.gov/pubmed/12323088?dopt=Abstract come to contradictory results regarding the antioxidant effectiveness of blueberries. Almost every variable that could be named was different between these two studies, but the author news report (not the review) blithely summarizes with: “Berry fruits contain high levels of antioxidants, compounds that protect cells from damage by harmful free radicals”. Antioxidants that aren’t demonstrated in the referenced papers to reliably show up in the bloodstream

    http://www.ncbi.nlm.nih.gov/pubmed/20028599?dopt=Abstract was another paper purporting the power of grape juice to prevent dementia. They recruited 12 people: statistical power fail.

    My complaint is that your news article (akin to Dr. Oz’s statements) leads one to believe that the connection is stronger than the underlying science. More fruit would be better for the average American, but let’s not overstate the claim.

  17. There’s always some latest, greatest food fad. In recent memory, just for fruit, we’ve had goji berry, acai, and pomegranate touted heavily. There’s also been some attempts to boost bananas, blueberries and raspberries, but the exotic ones are always the real sooper speshul Magic™. If your grandmother cooked with it, it’s no good. An apple a day? Dullsville.

    Grains are also high on the woo-food list, too. Why settle for boring old wheat and oats when you could have quinoa, amaranth or spelt?

  18. Jeff says:

    Always Curious,
    Two animal studies demonstrate blueberry anthocyanins cross the blood-brain barrier and show up in various regions of the brain:

    1. http://www.ncbi.nlm.nih.gov/pubmed/16053243
    2. http://www.ncbi.nlm.nih.gov/pubmed/20128604

    Avaliable human data is small-scale and preliminary. There is a longer history of research on grape seed extract (as opposed to grape juice), e.g., pubmed/21802563.

  19. Scott says:

    @ daedalus2u:

    Indeed. That’s what really bothers me about antioxidant claims – the fact that redox balance is so important, and therefore so carefully controlled by the body. If antioxidant levels in the diet could have a meaningful effect on that balance, well, we’d all be in BIG trouble because other things would vary it far more.

    It’s really a lot like the various woo about acidifying the blood.

  20. Angora Rabbit says:

    @Jeff,

    Take a closer look at the Methods section of the papers you cited. While the abstract sounds good, you’ll find that both have a fatal flaw (and frankly at Tufts they should know better!). Neither perfused the brains to remove blood contributions prior to measuring the anthrocyanins etc from the blueberries. So, in fact, they don’t know if the compounds actually crossed the BBB or are just of blood origin from the brain circulatory system. What they also failed to do was measure the blood levels separately and then demonstrate that the concentrations differed across the BBB, either accumulating or decreasing. This latter would actually give a (very gross) measure of the pharmacokinetics across the BBB.

    I learned this long ago when we began our studies of brain nutrient content. You absolutely must perfuse the tissue and remove the blood, or else you don’t know what compartment your compound is really in. Sadly I see this mistake all the time in the nutriceutical / supplement literature and grant proposals. So I shoot it down, and then the paper reappears in a low tier journal because the authors don’t want to repeat their expt and do it right. Sigh.

    So no, these papers did not show the compounds cross the BBB. I don’t fault you because there’s no reason why you should know about this. But the authors certainly should have known.

    And who in their right minds would publish a Morris Water Maze with only 4 rats per group? The error in those expts are typically large and generally a power analysis with 20% difference needs 8-10 per group. I really don’t believe that first one, especially since the behavioral data are massaged.

  21. jt512 says:

    Berries do not have a lot of calories. Blueberries, strawberries, and raspberries have 42, 25, and 32 kcal respectively per official USDA serving (1/2 cup), according to the USDA nutrient database.

    Jay

  22. RD says:

    @Angora Rabbit “NutriFashionista bandwagon”……Love it!!

    On a completely different topic (unless I stretch it into without more regulation on supplement companies and their claims, we will continue to have these glorified claims…..but what about companies making fearful claims)……

    If one of the contributers of science based medicine could comment on the ‘poisonous’ parabens in basically everything? I found an article on fda.gov…..but I like the way info is presented on science based medicine :)

    http://www.fda.gov/cosmetics/productandingredientsafety/selectedcosmeticingredients/ucm128042.htm

  23. Valya says:

    Personally, I’m waiting for the new bean craze. Several types of beans are chock full of antioxidants! Oh wait, beans are dirt-cheap and decidedly unsexy.

  24. daedalus2u says:

    I was just at a Gordon Conference on endocrine disruption in June, and one of the things that was emphasized was that the degree of sensitivity of the endocrine system to disruption depends on what it is doing at the time. If the cells that are doing signaling using hormones and receptors are proliferating or differentiating or “turning on”, then their sensitivity is orders of magnitude higher.

    Since adults are past most differentiation and proliferation (except for pathologies like cancer), adults are relatively insensitive to endocrine disruption. Being in utero is completely different. Going through puberty is completely different.

    It isn’t that the compounds are “poisonous”, but rather that they disrupt normal signaling and cause what ever that signaling was controlling to not work right.

  25. morris39 says:

    @daedalus2u
    Sorry this is off topic. I left a comment on your blog “Doctor’s Data sues QuackWatch” on Jul25. As there is no reply I wonder if you have not seen my comment or you’re not interested.

  26. kveldulf54 says:

    I don’t like Dr. Oz and I find it shameful that he has taken lingonberries for his purposes. My parents came from a Nordic country where eating lingonberry jam and drinking lingonberry juice is normal. I remember making the jam with my aunt as a little boy in that country.

    It makes me happy that a certain Swedish furniture shop sells these products, but I would prefer to think of it as a cultural product to be proud of, not something to be sensationalized on daytime TV with excessive health claims.

    @ Janet Camp: Lingonberry jam is not often used in desserts in Nordic countries. There is a certain breakfast diner chain here in the US who puts it on crepes and then says that it is Swedish–and yes, very dessert like–but this is not how we eat it there.

    It is generally treated the same way as cranberry sauce, put on meats, fish, mashed potatoes, casseroles–even in addition to a gravy. So, it is more of a garnishing on a main course. That said, it doesn’t go away after a holiday like cranberry sauce here in the US goes away after Thanksgiving, it stays around year round.

    I have heard it said that lingonberries have Omega 3, vitamin C, and solicylic acid (aspirin, as do cranberries) among other nutrients–though how much, I do not know. In any case, preserved as a jam Nordic people have been able to get these nutrients year round even when it is dark and snowy–possibly preventing scurvy before importing citrus fruits was possible.

  27. daedalus2u says:

    Angora, I did not miss the cherry craze. I have a writeup on cherries

    http://daedalus2u.blogspot.com/2008/05/is-secret-to-good-health-in-bowl-of.html

  28. Chris says:

    I love cherries, and I actually have a cherry tree. There is one major problem with eating them: they are also an excellent laxative. Never stray far from reliable plumbing after consuming cherries.

  29. Chris says:

    Oh, I forgot… for at least a full day.

  30. DevoutCatalyst says:

    Chris, you’re cherry picking the evidence…

  31. Calli Arcale says:

    Lingonberries are awesome. Full stop. Lately, I’ve taken to buying large tubs of plain yogurt and mixing it with lingonberry preserves for a nice snack. It really is excellent that way. And when I want a lighter lunch, a sandwich with plain cream cheese and lingonberries is fantastic. And as kveldulf says, they’re awesome on meat. Anywhere you’d use cranberry sauce, pretty much. Great on pork or turkey.

    I’m in a part of the US with lots of Nordic-derived folks, so we don’t have to just go to Ikea for it. Most of the major supermarkets around here carry it year round. Also pickled herring and gjetost. ;-)

  32. DevoutCatalyst says:

    Don’t forget the smoked eel.

  33. Chris says:

    I should pick up some lingonberries, I did try and fail at growing them in my garden. My son works across the street from a store that specializes in Scandinavian imports, including smoked eel. I picked up a Swedish/English dictionary there for my daughter, since she is going to start her college career this fall by taking Swedish (linguist majors need to have a certain amount of competence in three non-native languages).

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