Tuesday, December 8, 2009

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.

When I look at studies on longevity I the following factors appeared vitally important:

  • Very low alcohol consumption.
  • Virtually absent history of cigarette smoking. 
  • Genetics appears to play a large role. 
  • Typically lean, active individuals(for their age). 
  • Centenarians are not health nuts. In fact the only finding that Perls et al(Living to 100) uncovered was that the centenarians were generally people who preferred minimal food intake. 

Note the last point, I am not advocating caloric restriction. The caloric restriction era may well be coming to an end. As recent research further elucidates the the benefits of reduced food intake the evidence is now leaning to the amino acid balance that is more critical than CR itself. This is good news because CR has the following problems:

  • Reduces fertility. The loss of gonadal hormones could have serious implications beyond fertility.
  • Impaired immune function. This could be arising as an energy conservation strategy or it could be because a reduction in total fat intake may be impairing the immune response. Your immune system, like your brain, is very reliant on fatty acids.
  • There has been some evidence to suggest that sustained CR can cause structural changes to the brain. 
  • Loss of energy, feeling cold, are problems that people can encounter with CR. 

It is important to remember that the CR experiments were done in a laboratory. The real world, where animals must survive, is an entirely different matter.

Let us return to that last link from Medical News Today. There is an interesting statement in that news release which immediately caught my attention:

The fruit flies were fed a diet of yeast, sugar and water, but with differing amounts of key nutrients, such as vitamins, lipids and amino acids. The researchers found that varying the amount of amino acids in the mixture affected lifespan and fertility; varying the amount of the other nutrients had little or no effect.
The last phrase contradicts so much we think we know about health. It just seems obvious that boosting nutrient intake, particularly under a CR regime, should boost health longevity. Yet there has never been a study on humans that has proven that taking supplements improves health and longevity.

There is an important caveat here though: some medical conditions and life circumstances do appear to benefit from selective supplementation. All the studies in relation to heart disease and cancer are nulls and in some cases even negatives. Where there is a positive trend it is too weak for confidence. It may be statistically significant, but that is not necessarily of real world significance.

There are also some risks with supplementation. Smokers should avoid high beta carotene intake. There is advice that those with osteoarthritis should be wary of taking too much vitamin C. A recent study even raised concerns about folic acid supplementation and cancer risk. Worrying given that in Australia and other countries there are moves to fortify bread with folic acid.

A few years ago, on behalf of some friends whose daughter had been diagnosed with Stargardts Disease, a serious retinal degeneration disease that typically occurs in the teenage years and can lead to legal blindness. I investigated the possibility of metabolic therapy intervention. My friends had initially consulted a naturopath who immediately put the child on a high Vitamin A supplement. I hit the roof because I knew that was the last thing that should be done.Again, this is contrary to a "common sense" view but the data is very clear. A couple of months later the relevant medical authorities issued a specific warning against Vitamin A supplementation for individuals with Stargardts Disease. In spite of the findings from the AREDs and Blue Mountain Studies on Age related macular degeneration I am of the opinion that those with AMD should also be careful of their Vitamin A and pro-vitamin A carotenoid intake. If you keep reading you will see studies below which highlight that perhaps everyone should be careful about supplementing these nutrients.

The above example highlights how simple extrapolations based on the known functions of nutrients can lead us into very dangerous waters. The last example also offers a very important lesson: just because a nutrient is beneficial under normal physiological states does not mean it will have the same effect in pathological states.

Take vitamin C for an example. This vitamin is water soluble and washes out of the body very quickly. We really do need our daily source of Vitamin C and preferably spread out through the day to maintain appropriate levels. However once tissue saturation reaches a specific level any vitamin C ingested will be excreted. Additionally, in some conditions where inflammation is generating free iron, vitamin C is a nogo because it can exacerbate inflammation. The effect is so pronounced that experimental designs will use Vitamin C and iron to induce an inflammatory response. 

The counterpoint to this is that intravenous administration of Vitamin C does appear to offer some hope as a cancer treatment. A recent review strongly advocates a re-examination of this therapy. Another recent review indicates that that only through iv administration can therapeutic levels of vitamin C be achieved. As the abstract states:

According to pharmacokinetic data, parenteral administration of ascorbate decreased the growth rate of a murine hepatoma, whereas oral administration of the same dosage did not.

Antioxidants are all the rage at present but again the data on the benefits is lacking if not absent. At the cellular level there are a multitude of experiments proffering hope but at the physiological level there are so many different variables at play that we should be very wary of extrapolating from the cellular to the whole body. Life is not that simple, if it were we would not need to so much research that so often arrives at conflicting results which damn our most promising prognostications.

There is no data that supports antioxidant administration for the prevention of cancer. The positive findings that arose in previous years have been contradicted by later studies. I still find that hard to believe but on the basis of the current evidence what shall this man do? For one thing he can consider the commonly accepted view that most oxidative agents generated in our bodies are from either immune system, the mitochondria in nearly every cell, the normal hubadub of chemical reactions going awry, and various pollutants that enter our bodies. That last reference is there for a  purpose, under most physiological conditions the greater bulk of oxidative challenge is from mitochondrial respiration. While people worry about various chemicals, and the worry does have some justification, it is important to remember that oxidation is also an essential part of biochemical processes. The implication of this is that if one is to use antioxidants the target should be the dangerous products accruing in mitochondria.

The other big issue here is that in some circumstances at least providing high antioxidant loading may allow precancerous cells to escape death signals or immunological assault and progress to something we'd rather not think about. A key feature of some cancer cells is high expression of Heat Shock Induction Factor 1 (HIF 1). This transcription factor promotes the production of heat shock proteins, which are molecules of varying weights which can serve functions serving as chaperones for tranporting and protecting other proteins, to protecting molecules from damage, to even inhibiting death signals released from mitochondria.So cancer cells often already are at full alert and ready to fend off potential danger. Giving these cells the benefits of antioxidant loading may be giving some cancer or precancerous cells a survival advantage.

Despite the negative findings of antioxidants I am still of the opinion that in some situations antioxidant supplementation is warranted. For example, smokers are advised to increase their intake of vitamin E and C because smoking induces much more rapid degradation of these vitamins. Individuals with a family history of AMD or express high levels of drusen in in their retina should consider lutein and zeaxanthin supplementation. High levels of physical activity deplete antioxidant stores hence many athletes will address this with supplementation.

A large meta analysis of antioxidant supplementation suggested, albeit tentatively, that vitamin A, beta-carotene, and vitamin E supplementation might be increasing mortality. The vitamin A\beta-carotene finding does not surprise me because vitamin A plays a vital role in cell replication. Increasing Vitamin A levels may have the effect of promoting otherwise innocuous pin point tumours to become malignant. The vitamin E issue is more complex because supplements are typically loaded with alpha tocopherol, a rather poor Vitamin E variant. Additionally, it also impedes the absorption of the much more potent gamma tocopherol and tocotrienols. A recent study also found that vitamin E administration appeared to increase the risk of dementia. Again, I suspect this relates to the typical supplement containing alpha tocopherol. There are plenty of foods that contain good levels of vitamin E and tocotrienols.

It would be comforting for me to assert that the case is now closed: supplements are of no benefit for most people. But from an historical perspective a reasonable case can be mounted that at present that is an honest interpretation of the data but previous honest interpretations of the data suggested contrary outcomes. Then they argue that was because of poor design and ours is better. Sure ... On and on it's a bloody merry go round at times. If peer review is about sorting the wheat from the chaff than many reviewers must be starving to death.

So when I read how nutrient intake had little effect I was again reminded that the challenge of longevity and morbidity compression is not going to be met by filling our bodies up with "good molecules". I no longer think about "good" and "bad" functions and agencies of various biological entities. At a guess I suspect the problem is our propensity to identify objects as possessing intrinsic properties rather than appreciating how contextual dependency of the functions and agencies mediated by biological entities. One idea I have been playing with lately is that instead of "filling up the cells with good stuff" it may be more important to maintain an appropriate balance of nutrients and that there is an optimal concentration of nutrients and molecules generally that provides the best outcomes for all those chemical reactions. That is, "filling up cells with good stuff" is a fundamentally misguided strategy.

I'm sorry if you've read this far and were expecting an answer. I can't do that. I'm not even sure that providing generic nutrition advice, except in the broadest sense, to hundreds of people let alone billions of them, is a legitimate goal. For the individual who is serious about nutrition there is a lot of work to be done. Much reading, and always with a very critical eye, plus keep remembering all the "solid gold" health advice that years later turned out to be fools' gold. Nutrition through food, not molecules. If some people choose to use supplements as part of their lifestyle chances are the only real danger is to their wallet. Then there are those like myself who cycle through some supplement regimes, but I do this more with supplements that provide me with energy and cognitive boosts and I never sustain the regime for extended periods. We are entitled to our choices but on the basis of the present data, and my admittedly idiosyncratic view of physiological processes, I do believe that the persistent use of supplements are very often a waste of money.


Synaura said...

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