Monthly Archives: December 2012
DHEA and intracrinology at menopause, a positive choice for evolution of the human species.
Professor Emeritus, Laval University, Québec, Canada and Visiting Professor, College of Medicine, Al Imam Mohammed Ibn Saud Islamic University , Riyadh , Saudi Arabia.
Menopause has been chosen by evolution as the convergence of three factors, namely cessation of ovarian function (reproduction and estrogen secretion), high circulating dehydroepiandrosterone (DHEA), and intracrine enzymes able to convert DHEA into active sex steroids in peripheral tissues. The arrest of estrogen secretion by the ovaries at menopause causes a decrease of circulating estradiol below the threshold of biological activity, thus eliminating stimulation of the endometrium and risk of endometrial cancer. As much as the arrest of secretion of estradiol by the ovaries is essential to protect the uterus, it is of major importance that sex steroids continue to be made available in most other tissues which need estrogens and/or androgens for their normal functioning. Evolution, through 500 million years, has progressively provided the peripheral tissues with the enzymes able to make androgens and estrogens while high levels of DHEA, the precursor of all sex steroids, have appeared much later with the primates approximately 20 million years ago. All elements were thus in place for the functioning of intracrinology or the cell-specific formation of estrogens and androgens in peripheral tissues from the inactive precursor DHEA, with no significant release of active sex steroids in the circulation, thus eliminating the risks of adverse effects in the other tissues, especially the uterus. The presence of subthreshold levels of circulating estradiol combined with the formation of sex steroids from DHEA in specific peripheral tissues (intracrinology) makes menopause a positive characteristic supporting many years of good-quality postmenopausal life, useful for taking care of children and grandchildren. DHEA, however, decreases with age and is present at very different concentrations between different women, with the consequence that approximately 75% of postmenopausal women have too low circulating DHEA levels and suffer from symptoms/signs of hormone deficiency.
- [PubMed – as supplied by publisher]
There are no short cuts to improving your health and no magic bullets. Routine handfuls of vitamins will do you no good. In fact, randomised trials have repeatedly shown that people are actually worse off from popping vitamins.
Indeed, there’s no avoiding the fact that eating a wide variety of good food (lots of colours, more vegetables and fruit than dairy and meat) but not too much, keeping physically active, stopping smoking and making sure you don’t drink too much alcohol, are best. Boring, isn’t it?
Still, it’s the best way to avoid illness and disease. And of these, what scares people the most is cancer.
Two gentlemen in the waiting room of a practice I was working at were overheard by our reception staff chatting about a third, who had recently died.
“What did old Bill die of, then?” one asked. “I didn’t even know he was sick.”
“I don’t rightly know,” was the reply. “But I don’t think it was anything serious.”
Behind the apparent ludicrousness of this conversation is the implicit dread of cancer. Bill probably didn’t die of it. We would prefer to die of almost anything else.
The gender-specific cancer affecting women is breast cancer (although a very small number of men also get it). It runs neck and neck with lung cancer in causing more deaths and harm to women than any other. Luckily, we can do something about it because randomised trials have shown breast cancer can be detected by screening at the right age. And early detection and prompt treatment reduces the number of deaths from the disease.
But what about men? Is there something we can do to help them? The obvious contender is prostate cancer (women don’t have a prostate). It’s very common, it’s being diagnosed at increasingly greater rates, and causes a lot of early deaths (and harm).
So promoting screening for it is attractive. And it provides a nice symmetry. Women go off for their breast cancer screening at age 50, and their menfolk follow soon after. Of course, we know that men are much more reluctant to appear before the doctor, so we need something to encourage them. A sort of blokey message, “garn mate, y’know whatcha gotta do.”
Hence Movember. The trouble is we don’t know that screening for prostate cancer works.
That’s right. There’s huge controversy about it. There are advocates for screening (often those doctors who treat prostate cancer) and those who discourage it (especially public health and primary-care doctors).
The huge prostate cancer screening trials, equivalent to those of breast cancer from 20 or 30 years before, have only been published in the last year or two. And the results are ambiguous.
Some find a small benefit, and others none. It’s such a fine call that the evidence has done little to resolve the issue. Rather, experts are bunkering down to their prior beliefs, with each point of view finding some comfort in their interpretation of the trial data (which, it has to be admitted, is complicated and difficult to sort through).
All this means that one half of Movember, which aims to increase men’s awareness of prostate cancer and male mental health, is deeply flawed. Sadly, the campaign doesn’t focus on preventive activities we know to be particularly effective – stopping smoking, reducing alcohol consumption down from damaging levels, and doing more physical activity (although its website does mention them). Health promotion in this area is often unexciting and difficult, but we know it pays dividends in saved lives and avoided misery.
Instead, Movember focuses on something we are not certain is effective.
Worse than that, it might even be doing harm. Detecting cancer in men for whom treatment will confer no benefit is very damaging. Even the diagnosis is damaging. Men are nearly ten times more likely to commit suicide after being told they have prostate cancer.
And the treatment is damaging too. Despite real advances in the definitive treatment (“radical prostatectomy” – for which there are several methods), the chances are that most men will be rendered impotent by the operation, their penises will sink back, and the majority will develop urinary incontinence (temporarily for many – lasting for two years – but for some lasting well after even that).
All this is so counter-intuitive that it’s hard to explain. Surely, if you’ve got cancer, then treating it earlier must be better? Not necessarily. Only if we know that treatment is better than no treatment. And we don’t know that about prostate cancer.
If Movemeber focused more on the things that we know are effective, and steered off controversial areas which divide doctors, men would actually be much better off.
Simple, everyday activities can strengthen balance
If you love tennis, golf, running, dancing, or any number of other sports or activities, working on balance buffs your abilities. Not an athlete? Just walking across the room or down the block requires good balance. So does rising from a chair, going up and down stairs, toting packages, and even turning to look behind you.
And good balance helps prevent potentially disabling falls.
There is a lot you can do to preserve and improve your balance, and it doesn’t take special fitness classes or exercises. Incorporating balance and strength activities into your daily routine could be enough to keep you from falling.
Researchers in Australia tested a program called Lifestyle integrated Functional Exercise (LiFE) in a group of 317 people, ages 70 and older, who had fallen in the previous year. Participants were randomly assigned to one of three groups: the LiFE program, a structured exercise and strengthening program, or a control “sham” program of gentle exercises.
Those in the LiFE program incorporated balance and strength movements throughout their day — for example, squatting instead of bending over to close a drawer, or walking sideways while carrying groceries from the car to the house. At the end of one year, the LiFE group had experienced 31% fewer falls than the two other groups — a total of 172 falls, compared with 193 in the structured exercise group and 224 in the control group. People were also more likely to stick with the LiFE program than with the other two programs. To incorporate balance exercises into your daily routine, try standing on one leg while talking on the phone or sitting down in a chair without using your hands.
As we settle into the barbecue season, it’s time to consider whether the meat on your grill is harming your health. Conflicting messages in the media certainly don’t help. On one hand are advertisements with Sam Neill claiming red meat is the reason that humans are smarter than orangutans. On the other…
As we settle into the barbecue season, it’s time to consider whether the meat on your grill is harming your health. Conflicting messages in the media certainly don’t help. On one hand are advertisements with Sam Neill claiming red meat is the reason that humans are smarter than orangutans.
On the other, the prestigious World Cancer Research Fund reports that red meat may cause colorectal cancer. Whom to believe?
The good bits, and bad
Some red meat does contain fats our brains need. Omega-3 fats form part of the structure of brains and eyes, and may also help reduce blood pressure and modify inflammation. But meat isn’t the only food containing omega-3 fats. In fact, the richest sources are oily fish.
And if you buy grain-fed steak, you may be getting hardly any omega-3 fats at all. Grass-fed meat (and wild meats, such as kangaroo) is not only better for the environment, but better nutritionally, containing healthier fats and a lower fat content overall.
Red meat also contains decent amounts of zinc and protein, as well as iron, which is one of its big nutritional selling points. Indeed, the iron in red meat is in a form that our bodies absorb easily – “haem” iron.
Meat producers are fond of producing colourful ads that equate the iron content of a bucket-load of spinach with that of a small juicy-looking nugget of lean beef. And iron deficiency is an important issue – but that same haem iron may be harmful in fatty processed meat as you will see.
As well as beneficial nutrients, meat also contains saturated fat, the kind that promotes increased cholesterol levels in the blood and blocks blood vessels that the heart relies on to keep working.
The fat content of meat varies markedly with species and cut. If you buy untrimmed brisket, chuck or shoulder, or luxury marbled meat, such as wagyu or kobe beef, your meat will be around 10% to 20% fat. Ribs, neck, pork belly, and the cheapest minced meat can be up to 50% fat. You can get down to 3% to 5% fat if you trim your meat well of all visible fat and choose leaner cuts, such as loin and round steak, flank and shanks.
Meat and cancer
The cancer risk associated with high consumption of red meat, particularly processed red meat, is definitely cause for concern. In 2007, the World Cancer Research Fund (WCRF) produced an expert report that assessed the evidence for causal links between food, lifestyle and cancer, based on data from all studies that met quality standards.
In the report, the WCRF concluded that there was “convincing” evidence (that is, evidence of both the mechanism and the effect) for a link between colorectal cancer and high intakes of red meat. The link was strongest for processed red meat – bacon, salami, sausages and hot dogs, which contain curing agents such as nitrates and nitrites.
The studies’ data indicated that cancer risk continued to rise with higher meat intakes. This rise appears to start once red meat consumption exceeds 300 grams in a week. The WCRF’s recommendation is that people who eat red meat should consume less than 500 grams a week, including very little if any processed meat products. There was no data to indicate that any level of processed meat intake was free of risk.
Eating fish may help reduce colorectal cancer risk, and some studies indicate that a high fibre intake, and eating lots of fruits and vegetables, are associated with reduced cancer risk.
How it works
How red meat causes the increase in cancer risk is still a question in search of a complete answer. Many different components of meat have been suggested as a mechanism, including the curing agents nitrate and nitrite that are present in processed meat; the fat or the haem iron in meat; the excess protein load that big meat eaters might often consume; and the carcinogens, such as heterocyclic amines (HCAs)and polycyclic aromatic hydrocarbons (PAHs), that can be formed during the cooking of meat.
Protein doesn’t appear to be the culprit, despite the fact that the end products of excess protein intake are quite toxic (these are excreted if the kidneys are working normally). Unlike high-protein diets, high-fat diets have been shown in animal studies to increase cancer risk, apparently promoting gut cancers through their damaging effects in the gut as well as contributing to obesity, which itself is a cancer risk factor.
But studies of low-fat diets haven’t shown a reduction in risk, so other factors may also be involved. The problem with processed meat seems mainly to stem from its salt content (associated with risk of stomach cancer) and its content of nitrates and nitrites, which are added as part of the curing process and can be converted to carcinogens.
And unlike the iron in plant foods, the haem iron in meat seems to help produce mutagens and carcinogens in the meat and in the gut by reacting with the fat in the meat, and by helping to convert nitrates and nitrites to their carcinogenic form.
There are a lot of studies showing that the carcinogenic substances HCAs and PAHs are produced when you cook your meat at a high temperature or on an open flame, and that colorectal cancer risk increases when you consume a lot of these. Some people have a genetic sensitivity to HCAs and they’re at even higher risk.
Mysteriously, although barbecuing chicken and seafood produces large amounts of HCAs, these don’t seem to be associated with increased cancer risk, perhaps because they are different types from the ones that red meats produce. And perhaps their lower iron content has something to do with it.
Cooking for shorter times, or at lower temperatures, produces smaller amounts of HCAs and PAHs. Raw meat, surprisingly, is no less digestible than meat cooked briefly either at high or low temperatures. What really makes a difference in digestibility is overcooking until meat is tough. This reduces digestibility significantly but that increases again in long, slow cooking.
The magic of marinades
Interestingly, marinating meat may be a good idea for health as much as for flavour. A Portuguese study found that several hours’ marinating in beer or red wine significantly reduced the production of HCAs in beef, perhaps by reducing movement of precursor substances to the surface of the meat, or by adding antioxidants that inhibit the reaction.
Other studies have successfully used garlic, rosemary, thyme and sage, and olive oil with garlic and lemon. Cooking with extra-virgin olive oil had a similar effect. But adding sugar or fruit to marinades appears to increase the risk of burning and forming more carcinogens.
So, as you wheel out your barbecue this summer, consider serving sustainable seafood or organic chicken some of the time instead of red meat; stick to smaller serves of grass-fed lean meat, marinated without sugar or salt and cooked to a juicy medium-rare, away from a bare flame; and have plenty of salad with your meal. Food for thought?