High-altitude wines have been lauded for deeper colour, better structure and increased concentration. But what about their health benefits? Jamie Goode looks at the hot topic of resveratrol and asks whether this so-called superdrug has raised more hype than hope
Grapes grown at altitude taste different. As you go higher, temperatures drop and the fruit is exposed to more ultraviolet (UV) light. Higher UV leads to higher levels of anthocyanins (and therefore darker-coloured wines) as well as enhanced production of protective compounds – most notably the phytoalexin resveratrol.
Resveratrol is a wonder drug that protects against heart disease and has semi-magical, life-prolonging properties.
Is that the story of high-altitude wines in a nutshell? Sadly not. While bits of this appealing (and potentially important) story are true, such a simple overview is in
danger of becoming part of the established body of wine knowledge on rather slender evidence, chiefly because journalists who cover it are unable to evaluate the scientific literature in an appropriately critical manner.
Sardinia and polyphenols
The story really begins with some centenarians in Sardinia, who came to the attention of London-based medic Roger Corder at the William Harvey Research Institute. Dr Corder, who has an interest in cardiovascular disease, discovered that the mountainous Nuoro region of Sardinia had far more than its fair share of 100-year-old residents, and so reasoned that there could be something special about their diets that was enhancing their health. And because these people were eating a lot of meat, cheese and pasta, which aren't usually associated with good health, he suspected that there might be something special about the local wine they were drinking.
Corder is responsible for an important thread in the wine-is-good-for-you story. His research emphasis is atherosclerosis, or how damage occurs to major blood vessels, and his big discovery was that polyphenols from red wine stop the formation of a compound called endothelin 1 (ET1). ET1 causes blood vessels to constrict, which encourages development of atherosclerosis.
This fits in with other research showing that red wine modifies the function of the endothelium, a layer of cells lining the inner surface of blood vessels. Endothelium damage is the first stage of atherosclerosis, so if red wine could prevent these early events, then it is likely that it could stop the development of heart disease.
Corder had already examined the effects of a range of red wines on the development of atherosclerosis, and found the higher their polyphenol content the better they could suppress ET1. Back to Sardinia. Seeing as most of the centenarians drink strictly local wines, it seemed worth having a look at them. Analysis showed that they were all good at suppressing ET1, and the wine from Nuoro itself, grown on the island's highest vineyards, was best of all. The story seemed to fit: wines grown at altitude are exposed to the highest levels of UV light, and UV light induces polyphenol synthesis in the grapes. And wines richer in polyphenols seem to be more effective in inhibiting ET1.
Argentina and altitude
Now consider Argentina and the high-altitude vineyards in the Mendoza region. In 2001, Dr Laura Catena of the Catena winery initiated a research project, called Ultimo, looking at the effects of altitude. The results are two years away from being ready for publication, but preliminary findings were reported by winemaker Mariela Molinari at a recent seminar in London.
Perched on the side of the Andes, Mendoza is a unique region where the vineyards are found at a range of altitudes: Catena's range from 780m above sea level in Este Mendocino to 1,500m in Valle de Uco. These different altitude vineyards can be matched to different varieties, but in the Ultimo project Catena has examined how Malbec performs with varying elevation. Molinari's presentation emphasized two different environmental variables that change with altitude and influence vine growth: temperature and sunlight – in particular UV light.
During vine growth, two key processes are occurring in tandem: respiration and photosynthesis. Temperature speeds up both, and for every 100m increase in altitude average temperatures decrease 1ºC in the important ripening months of March and April. However, while respiration increases in rate with rising temperature, photosynthesis stops abruptly when the ambient temperature reaches about 32ºC. This is because the vine is doing a trade-off: it wants to photosynthesize, but to do this it has to open its stomata or gas exchange pores in the leaves. To exchange gas, the vine risks losing water vapour. There comes a stage, at a combination of temperature, relative humidity and wind, where the gain from photosynthetic activity is outweighed by the risk of water loss, and so the vine shuts down and stops growing.
At lower altitude, temperatures frequently pass 32°C during the growing season, while at higher altitude they seldom do. However respiration will continue irrespectively, and the result during the ripening period is that acidity levels drop off sharply in the warmer vineyards at 780m, while they decrease more slowly at the cooler 1,500m sites. This permits a longer hang time in high-altitude vineyards. It seems also to be beneficial for the vines to not have respiration continuing in the absence of photosynthesis, and this could be one reason for the supposed superiority of vineyard sites with a marked diurnal temperature swing: cold night-time temperatures would slow respiration markedly.
But it is not just temperatures that change with increasing altitude: as temperatures decrease, sunlight intensity increases. The concept of 'degree days' on its own is of limited use here. Catena's research has looked at what happens to polyphenols of black grapes at varying altitudes – and the results are very interesting. Grapes grown at 1,500m have an average skin thickness of 2.5mm, whereas at 840m they are 1.1mm. This is a striking, and likely significant, difference, as skins are such an important aspect of red wine making. Indeed, the levels of anthocyanins (the pigmented compounds in grape skins) increase with altitude. Total polyphenols increase faster at 840m during ripening, but then dip and are overtaken by the grapes at 1,500m, whose levels then keep rising while the levels at the lower site decline.
Additionally, grapes at lower altitude produce lots of astringent monomeric tannins, while the higher vineyards produce similar levels of monomeric tannins but much more of the desirable polymeric tannins. The result of all this? 'The higher you go, you get a higher concentration of total polyphenols, lower proportion of monomeric tannins with respect to polymeric tannins, and you increase concentration of floral and fruit aromatics,' explains Molinari. 'All this translates into Malbec wines with less bitterness and astringency and at the same time more concentration. The results are concentrated wines that are soft and supple.'
Hitting the headlines
The final observation relates to resveratrol levels. This wannabe wonder drug belongs to a class of plant defence molecules called phytoalexins. These are synthesized by plants to protect them from fungal disease, and levels are elevated in response to attack. Of course, grapes grown where disease pressures are high are likely to have higher levels of resveratrol, but then most wineries remove any damaged or rotten grapes because they are so detrimental to wine quality. Fortunately, resveratrol is also synthesized in response to UV light, so it's possible to get high levels in healthy grapes grown at altitude. Catena has shown that Malbec grown at 840m has 12mg/l of resveratrol, but this almost doubles in vineyards at 1500m to 23mg/l.
Resveratrol has been in the news a lot lately. Two scientific papers were published in November 2006, both of which were picked up by science journalists and the resulting stories made a big media splash. The first, published in Nature, showed that resveratrol offsets the ill-effects of a high-calorie diet in mice and extends their lifespan. The second, in Cell, showed that resveratrol improves mitochondrial function and prevents metabolic disease, again in mice.
A puzzling, somewhat paradoxical observation is that giving animals only just enough food to survive prolongs their lives, often quite markedly. The reasoning behind this is that if food is plentiful, you want to get on with life, have offspring and, once they are reared, get out of the way so you are not competing with them for resources. Yet, if food is scarce, you want to delay reproducing and hang in there, hoping that things will change – hence an extended lifespan. A complex set of signalling molecules have been implicated in this control of metabolism, and this is where resveratrol comes in.
Resveratrol seems to affect one of the key metabolic signalling molecules, SIRT1. This is a hot topic at the moment because of the growing crisis of obesity and associated metabolic diseases such as diabetes and cancer. Hence attention has turned to signalling molecules such as SIRT1, which is involved in metabolic regulation. If we can target these molecules with drugs or dietary interventions, we can get fat people to lose weight without getting them to eat less, and we can all live the good life without piling on the pounds. And by avoiding diseases such as diabetes and atherosclerosis, we can live longer.
Cause for concern
However, despite the fascinating science involved, there is one major hurdle – the bioavailability of dietary resveratrol. Before we get too excited about wine-borne resveratrol and its possible health-enhancing effects, we need to know that there's enough present in red wines for an effect to occur. If there is, we then need to know what happens to resveratrol in the gut. Is it taken up in the intestine? Does it get into the bloodstream? How long does it last?
First, is there enough resveratrol in wine for it to have an effect on SIRT1? Even resveratrol advocates admit that to achieve the sorts of doses the mice were fed in experiments would be impossible through drinking wine. For this reason, some companies are busy developing resveratrol supplements that deliver high doses in the sort of range that work in mice.
'The resveratrol story has become a bit of a publicity stunt for those who lack knowledge in the field,' says Corder. 'At a dose of 22.4mg/kg per day [as used in the recent mouse study reported in Nature] and typical resveratrol levels of 1-2 mg/litre in wine, the dose in human terms would have to be around 1,568 mg/day or 780-1,560 litres of wine per day.'
More problematic is the bioavailability story. Data in humans are limited, and they threaten to rain on the resveratrol parade. Professor Thomas Walle at the Medical University of South Carolina published a damning paper about this in 2004, in which he concluded that, in humans, very little dietary resveratrol gets to where it is needed in the body. 'Based on our studies, as well as those of others, the bioavailability of resveratrol – that is, the amount of intact resveratrol reaching the blood circulation – is virtually zero in humans,' Walle says. So, there are some questions that remain to be answered, and it really is too soon to be making firm conclusions.
But the idea that high-altitude wines might have health-promoting properties could still prove to be a fruitful area of research. Corder has been collaborating with Catena (also a medic) on looking at high-altitude wine polyphenols and their effect on ET1. 'We found that, up to 1,220m elevation, there was an upwards direct correlation between altitude, procyanidin levels and ET1 inhibition potency,' explains Catena. 'Above 1,220m there was no further increase. We also found that Cabernet Sauvignon wines from high altitude were more potent ET1 inhibitors than Malbecs, although the Malbecs were quite potent as well.'
Catena hasn't given up on the resveratrol story. 'Some day we may find that it does explain part of the health benefits of wine,' she asserts. 'Furthermore, although I agree that nobody has conclusively shown that resveratrol has any beneficial health effect, I am not as sceptical as Dr Corder is about the future of resveratrol research. I am optimistic that some day we will find a way to make resveratrol, whether it be from wine, chocolate or cranberries – and perhaps also procyanidins, bioavailable and of some health benefit.'
Grapes grown at high altitude are different. Because of cooler temperatures and higher sunlight intensity, a longer hang-time is possible with higher acidity, deeper colour, more and better tannins and higher levels of resveratrol. All but the latter have the potential to enhance wine quality, suggesting that winemakers would be well-advised to look for higher sites solely for this purpose. But the issue of resveratrol concerns many scientists (this writer included), who are worried that the wine industry will make claims about the health-enhancing effects of wine that simply haven't yet been substantiated. If it eventuates that dietary resveratrol has important effects in humans at the concentrations found in wine, then that's a bonus for lovers of full-bodied reds. But current evidence doesn't look all that good.
Well-made, high-altitude red wines should be highlighted in the press not because they might help us live longer, but simply because they taste good.
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