Sunday, December 02, 2007


This is geninely interesting work but hyping it as linked to the alleged beneficial effects of red wine and resveratrol is a stretch. The authors themselves decribe the new molecules as "structurally unrelated to" resveratrol. Whether the results transfer from rats and mice to people remains to be seen, however. Side effects could also be a concern. Popular summary below followed by journal abstract:

Millions of people with adult diabetes could one day be treated with a drug based on the healthy ingredient of red wine which could even help prevent other diseases linked with old age. The new class of drugs, which will be tested on patients next year in Europe or the US mimics the effects of a reduced-calorie diet, which is known to extend the lifespan of a wide range of creatures, from worms to mice and monkeys. They work in the same way as resveratrol, the chemical in wine and grapes thought to deliver some of the proposed health benefits and explain the "French paradox," referring to how the French suffer relatively low incidence of coronary heart disease, despite having a diet relatively rich in saturated fats. [It's no paradox. There is no harm in saturated fats]

The problem with red wine is that earlier animal research suggested that around 1000 glasses would have to be consumed each day to take enough resveratrol to reduce the impact of a high fat diet, increase stamina two fold and significantly extend lifespan. Now new compounds have been developed that are roughly 1,000 times more potent than resveratrol and are also 1,000 times better at staving off the development of type 2 diabetes, report researchers led by Christoph Westphal of the company Sirtris Pharmaceuticals, Cambridge, and David Sinclair of Harvard Medical School, in today's Nature. "The novel drug candidates we have identified can potentially unlock a whole new approach to treating Type 2 Diabetes," stated Dr Jill Milne, lead author of the study.

Type 2 diabetes occurs when the body becomes insensitive to the effects of the hormone insulin and it seems that the new drugs can boost insulin sensitivity substantially. The new drug candidates work by activating a protein called SIRT1, which influences the ageing process and functions to ensure that the body remains receptive to the activity of insulin. The compounds potentially offer an important new avenue for developing treatments to tackle diseases linked to ageing and poor diet.

"The new drug candidates represent a significant milestone because they are the first molecules that have been designed to act on genes that control the ageing process. " For this reason, we feel they have considerable potential to treat diseases of ageing such as Type 2 Diabetes," said Dr Westphal. "The breakthrough in potency we have achieved means that we can obtain the health benefits of resveratrol with a considerably lower dose." "If all goes well, SIRT1 activator drugs could be available on the market as early as 2012 or 2013," he told The Daily Telegraph.


Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

By Jill C. Milne et al.


Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes1, 2. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity3, 4, 5, 6, 7, 8, 9. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival10, 11, 12, 13, 14.

Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.

Nature 450, 712-716 (29 November 2007)

Pomegranates to the rescue?

It's a good thing these results were not statistically significant. Antioxiodants shorten your life so choosing between a longer life and better erections would be a Devil's bargain! Popular summary below followed by journal abstract:

Pomegranate juice can give men a boost in the bedroom according to scientists. A daily glass can act like Viagra, new research shows. Nearly half the men who drank it for a month in the American study said they found it easier to rise to the occasion, reports The Sun.

It is thought the juice is rich in antioxidants which increase blood supply to the penis. Just like drugs for impotence, the antioxidants raise levels of nitric oxide, which relaxes blood-vessel walls.

Fifty-three volunteers aged 21 to 70 with mild to moderate problems drank 8fl oz with their evening meal. Researcher Dr Christopher Forest, of the University of California in Los Angeles, said: "Pomegranate juice has great potential in the management of erectile dysfunction."

Pomegranates have already been hailed a superfruit capable of reducing the risk of heart disease and preventing prostate cancer. The fruit is believed to have more antioxidants than any other juice, tea or red wine.


Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study

By C P Forest et al.


This randomized-controlled trial examined the efficacy of wonderful variety pomegranate juice versus placebo in improving erections in 53 completed subjects with mild to moderate erectile dysfunction. The crossover design consisted of two 4-week treatment periods separated by a 2-week washout. Efficacy was assessed using International Index of Erectile Function (IIEF) and Global Assessment Questionnaires (GAQ). Of the 42 subjects who demonstrated improvement in GAQ scores after beverage consumption, 25 reported improvement after drinking pomegranate juice. Further, 17 subjects showed preference of one beverage to the other. Subjects were more likely to have improved scores when pomegranate juice was consumed (P=0.058). Although overall statistical significance was not achieved, this pilot study suggests the possibility that larger cohorts and longer treatment periods may achieve statistical significance.

International Journal of Impotence Research (2007) 19, 564-567


Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

9). And how odd it is that we never hear of the huge American study which showed that women who eat lots of veggies have an INCREASED risk of stomach cancer? So the official recommendation to eat five lots of veggies every day might just be creating lots of cancer for the future! It's as plausible (i.e. not very) as all the other dietary "wisdom" we read about fat etc.

10). And will "this generation of Western children be the first in history to lead shorter lives than their parents did"? This is another anti-fat scare that emanates from a much-cited editorial in a prominent medical journal that said so. Yet this editorial offered no statistical basis for its opinion -- an opinion that flies directly in the face of the available evidence.

Even statistical correlations far stronger than anything found in medical research may disappear if more data is used. A remarkable example from Sociology:
"The modern literature on hate crimes began with a remarkable 1933 book by Arthur Raper titled The Tragedy of Lynching. Raper assembled data on the number of lynchings each year in the South and on the price of an acre's yield of cotton. He calculated the correla-tion coefficient between the two series at -0.532. In other words, when the economy was doing well, the number of lynchings was lower.... In 2001, Donald Green, Laurence McFalls, and Jennifer Smith published a paper that demolished the alleged connection between economic condi-tions and lynchings in Raper's data. Raper had the misfortune of stopping his anal-ysis in 1929. After the Great Depression hit, the price of cotton plummeted and economic conditions deteriorated, yet lynchings continued to fall. The correlation disappeared altogether when more years of data were added."
So we must be sure to base our conclusions on ALL the data. But in medical research, data selectivity and the "overlooking" of discordant research findings is epidemic.


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