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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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