A Counter Intuitive Study on Longevity

There is no easy way to establish strategies for living a long life. This news release adds to our confusion. I proffer the following cautions:

1. This study contradicts many other studies. When that occurs don't accept the study at face value, it needs to be subject to critical review by many people, and believe me that is far superior to peer review! 
2. This study is relying on data gathered a very long time ago, when experimental methods were much less refined than today. 
3. It relates to analysis of "more than 1500 bright children". Small sample, and just what do they mean by "bright". 

The new release does not point to a published paper, the results are being published in book form. I would much prefer that they first publish a series of papers then publish their book. By publishing the book first they are putting out a view on longevity that has not been subject to (1) above.

For myself at least I have to disregard the claims of this news article. Yes I can see elements that I find plausible but in the absence of a series of papers that have been subject to critical review and discussion by a wide range of people it is virtually impossible to know if all their conclusions are valid.

There is a good lesson here in relation to health news. There are also sorts of claims being made about the secrets to longevity. There are no secrets, we're still learning, but obviously a good deal of common sense goes a very long way. Eat well, exercise regularly, and don't go looking for fountains of longevity.

Professor Patrick Holford - Nutrition Nonsense

The other day I picked up this text and late last night decided to read the chapter Professor Patrick Holford because I read a book of his some years ago. Ben Goldacre is a British doctor who writes regularly for the Guardian and has taken up the challenge of addressing all the kookiness out there in relation to health advice. Good on him, high time the medical profession put some effort into attacking the multitude of spurious nutrition advice out there. I may provide a full review of "Bad Science" later but for now I will focus on this Patrick Holford character.

Nutrients and Longevity

Today I read an interesting article in the New York Times that reminded me of earlier studies I had read. To read the full article you need to register with the NY Times. That is free and I recommend it because the health articles are amongst the best I've encountered in the mass media. (They will protect your privacy.) Balanced, referencing actual research, and the articles are very easy to read. The companion articles in relation to this issue can be read here, and here.

Antioxidants - A Risk Benefit Profile

Antioxidants are all the rage these days. Paradoxically, while there are many in vitro studies demonstrating potential benefits from antioxidants, and many studies indicating their utility in various pathologies, there is scant evidence that antioxidant supplementation prolongs life.

I have concerns about the absorbing huge doses of antioxidants. Oxidation is an intrinsic and vital physiological process, filling up your body with antioxidants may sound like a good idea but how often have we been subjected to the latest nutrition craze only to find that it was nonsense? Far too many times, there needs to be much caution in the use of antioxidants. This recent study highlights that while antioxidants have considerable therapeutic promise, indiscriminate use of antioxidants can also lead to pathological processes.

One thing not mentioned in this study but is very important is the use of alpha tocopherol, typically and misleading referred to as Vitamin E. There are in fact a number of types of vitamin E and high consumption of alpha tocopherol can reduce the concentrations of gamma tocopherol and delta tocopherol, both of which are better variants than alpha tocopherol. . This may explain why some studies have found that high dosages of alpha tocopherol can increase mortality. The reason why most vitamin E supplements only contain alpha tocopherol is simple: it is the cheapest to manufacture. If you want a good source of vitamin E use wheatgerm. Note what the below study found in relation to wheatgerm:

Intriguingly, the combined treatment with wheat germ and vitamin C profoundly inhibited metastasis formation in various tumor models of different origin (Lewis lung carcinoma, B16 melanoma and human colon carcinoma xenografts [HCR25]) [61]. On the contrary, wheat germ had no toxicity on peripheral blood leukocytes (PBLs) at doses that affected tumor cells. The crude powder extract of fermented wheat germ inhibits nucleic acid ribose synthesis primarily through the non-oxidative steps of the pentose cycle [60]. Curiously, another quinone compound, carnosic acid quinone, like wheat germ, recovers potent antioxidant activity upon standing [62].

Note that last sentence, that the antioxidants in wheat germ "recover" their antioxidant activity. Now whether or not this happens in the body is another question but given that wheat germ is cheap and a valuable nutrient source why bother with all those expensive supplements?

This study also highlights that certain antioxidants, at high doses, can actually induce oxidation. Ever since that now famous study on beta carotene which found it increased the rate of lung cancer in smokers(as if that were possible!) I have harbored suspicions that beta carotene should not be added to multi vitamins. Smokers should definitely avoid beta carotene in vitamin pills and problem be careful about the intake from natural sources. As for non smokers, the data is equivocal. Beta carotene does not appear to be a causative factor for or against developing cancer.

Ascorbic acid, a variant of vitamin C, appears to be a double edged sword. At high doses it can stimulate the production reactive oxygen species, particularly in the presence of free iron, the latter often being present in inflammatory conditions. Mega dosing of vitamin C is a waste of money and can damage the gut. Once tissue saturation of vitamin C is achieved there is little point in swallowing vitamin C tablets because it will not pass the gut wall. Smokers should increase their intake of vitamin C has it has been shown to help preserve vitamin E levels. As with most antioxidants, it is generally better to consume these throughout the day because this will help maintain tissue levels through the course of the day, whereas consuming antioxidant rich foods or supplements at one time of the day will lead to depletion until topping up occurs at the next meal.

The flip side of megadosing for vitamin C is recent studies which found that intravenous injections of vitamin C may have therapeutic use in treating some cancers.

The below study can be downloaded at this site.

Reading
Article
The role of antioxidant supplement in immune system, neoplastic,
and neurodegenerative disorders: a point of view for an assessment
of the risk/benefit profile
Authors
Daria Brambilla1, Cesare Mancuso2, Mariagrazia Rita Scuderi1, Paolo Bosco3,
Giuseppina Cantarella1, Laurence Lempereur1, Giulia Di BenedettoLL0000001,
Salvatore Pezzino1 and Renato Bernardini*1
Journal
Nutrition Journal 2008, 7:29 doi:10.1186/1475-2891-7-29
Location
Life\Nutrition\
Date obtained
2/11/2008
Date Read
7/11/2008
Date to Review
Web Page
http://www.nutritionj.com/content/7/1/29
Keywords
Printed
Notes
Abstract
This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.

Wines and Heavy Metals

For years we have been advised that a glass or two of wine is good for us and then this pops up. The basic message is: some European wines have such extraordinarily levels of heavy metals that even a single glass could be bad for our health.

There is an important nutritional lesson here and it is this: we're ignorant. For all the research that goes on we are a very long way of knowing what exactly constitutes good living. The research must proceed but please be very careful with health reporting. It is so very difficult to draw conclusions from a group of studies let alone a single study. Whatever you do with regard to your health always stick to the essentials. Experiment with diet and supplements, where possible do this in the context of regular blood tests so as to determine the effects. Remember, studies are statistical, the results of a particular study may be completely you irrelevant for someone living your life and with your physiology.

At the end of the day, all of us have to find out what works for us healthwise.

Eat slowly, eat well, with friends and\or family

In our fast paced world eating has taken on a utilitarian aspect that is not doing us any good at all. We read the labels for nutrients, we pop pills for health, we eat on the run, we avoid unhealthy foods, we have turned eating into a chore when it should be a pleasure.

Even supermarkets are now selling various supplements, foods are fortified with this and that, purportedly claiming superior health from eating these fortified foods. The evidence for this is scant. What epidemiological studies show is that you don't need a "scientifically" determined eating plan but rather observing some simple rules for eating healthily.

The French Paradox remains unresolved. Basically it goes like this: the French eat a great many unhealthy foods yet have markedly lower rates of the types of diseases that pervade many Western countries. The French enjoy their food, eat as a social event not as an intrusion on a busy life. They take time to enjoy their food, eat much more slowly than us, and enjoy their meals.

Now consider how many of us eat: we agonise of the right balance of foods to optimise health, we eat lunch quickly so that we have more time to enjoy our lunch break before going back to the grind, we get home from work and are so tired we slap dash something together and gulp it down while watching TV or on the internet instead of using meal time as a chance to socialise and unwind.

This latest study from the BMJ highlights a problem with our eating style. It found that eating quickly and until we are full is a risk factor for obesity. No surprises there. The feeling of being full arises when food reaches the stomach, hormones are released which signal that we have had enough to eat. However if we eat quickly the hormonal message doesn't begin to function until we have over eating. This is because it takes time for food to reach the stomach. The other problem with eating quickly is that we tend to insufficiently chew our food. This prevents nutrient absorption.

We need to change our eating habits. We need to return to the habits of enjoying eating rather than treating it as a scientific exercise. We need to eat with others, take our time, enjoy our meals, and stop obsessing about food and nutrients.

Antioxidants, Neurodegeneration, and Cancer

Research article. Interesting but lacking depth. Good balance on the issue of antioxidant supplementation.

The study can be downloaded here.

Article:
The role of antioxidant supplement in immune system, neoplastic, and
neurodegenerative disorders: a point of view for an assessment of the
risk/benefit profile
Authors:
Daria Brambilla, Cesare Mancuso,Mariagrazia Rita Scuderi,Paolo Bosco,Giuseppina Cantarella, Laurence Lempereur, Giulia Di Benedetto, Salvatore Pezzino, Renato Bernardini,
Journal: Nutrition Journal 2008, 7:29 doi:10.1186/1475-2891-7-29
Location: Life\Nutrition\title
Date obtained: 3/10/2008
Date Read: 19/10/2008
Date to Review:
Web Page:
Printed:
Notes:
Abstract
This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.
--
However, several clinical studies demonstrated that not only malnutrition, but also the excess of certain nutrients (e.g. iron, alphatocopherol, beta-carotene, ascorbic acid) may set into motion oxidation phenomena and, therefore, cell injury [8,9]. Thus, it is of relevance that prior to considering introducing antioxidant therapy into mainstream medicine, significant advances in basic cell biology, pharmacology and clinical bioanalysis will be required.
--
Heme oxygenase is a microsomal enzyme which metabolizes heme into ferrous iron, carbon monoxide and biliverdin (BV); the latter is then reduced by BVR into bilirubin (BR), a molecule endowed with strong antioxidant and antinitrosative activities [11-14]. Interestingly, all these protective factors act in a concerted way, enhancing the antioxidant defense system of the cell. When the balance between ROS/RNS and antioxidants turns in favor of the former, oxidative/nitrosative stress occurs.
--
Extracellularly generated ROS can diffuse through anion channels into the cytoplasm; the resulting variation in the cell redox state leads to modulation of an array of transcription factors (eg. NF-kB, AP-1), protein kinases (e.g. AKT, JNK, p38), and receptor activated MAP kinases involved in apoptosis [17, 24,25,26]
--
However, not only immune cell produce ROS necessary for the microbicidal activity, but they are also sensitive to external ROS, due to their high polyunsaturated fatty acids (PUFA) content. Immune cells are atypical, as compared with other somatic cells, in that they contain high levels of antioxidant vitamins, presumably providing protection against lipid peroxidation and immunosuppression, both of which are well known risks posed by high PUFA content [38].
--
Intriguingly, the combined treatment with wheat germ and vitamin C profoundly inhibited metastasis formation in various tumor models of different origin (Lewis lung carcinoma, B16 melanoma and human colon carcinoma xenografts [HCR25]) [61].
61. Hidvégi M, Ráso E, Tömösközi-Farkas R, Paku S, Lapis K, Szende B: Effect of Avemar
and Avemar + vitamin C on tumor growth and metastasis in experimental animals.
Anticancer Res 1998, 18(4A): 2353-2358.
--
Heme oxygenase-1, the inducible isoform of HO, is a key protein in the cell stress response and its up-regulation is a common event during pro-inflammatory conditions [11,69-72]. Recent work clearly demonstrated that regulatory T cells overexpress HO-1 and release CO under pro-oxidant conditions. Carbon monoxide may inhibit the proliferation of effector T cells, thus reducing the immune response and prevent autoimmunity and/or graft reaction [73,74]. Dietary antioxidants, in particular polyphenols, has been shown to increase HO-1 expression in different in vitro systems [3,75,76] and the potential use of this natural substances to regulate immune response should be carefully addressed.
--
Other studies report that combination of vitamin A and other antioxidants, significantly increases mortality related to neoplastic diseases. [91]. According to these studies, selenium would be the only element displaying beneficial effects, as it has been shown that it reduces total cancer incidence, an apparently sex-related effect, as it is predominant among males, rather than in females [89].
--
Due to their scarce bioavailability, only a negligible amount of polyphenols reaches brain tissue and the concentrations achieved are much lower than those efficacious in vitro [3]. As far as NSAIDs, ad hoc designed clinical trials with a large number of patients, clearly demonstrated that these drugs do not have any significant effect in slowing cognitive decline in patients suffering from mild-to-moderate AD [120,121].
--
It is noteworthy to underlie that as for all drugs, antioxidants may give important side effects if not correctly used or in combination with other drugs. Vitamin A, E and â-carotene for instance, have been shown to have pro-oxidant effects at higher doses or under certain conditions [39].
--