Princess Health and Sunscreen and Melanoma.Princessiccia

Princess Health and Sunscreen and Melanoma.Princessiccia

cancer

Gusty 11:40 Add Comment

Melanoma is the most deadly type of skin cancer, accounting for most skin cancer deaths in the US. As Ross pointed out in the comments section of the last post, there is an association between severe sunburn at a young age and later development of melanoma. Darker-skinned people are also more resistant to melanoma. The association isn't complete, however, since melanoma sometimes occurs on the soles of the feet and even in the intestine. This may be due to the fact that there are several types of melanoma, potentially with different causes.

Another thing that associates with melanoma is the use of sunscreen above a latitude of 40 degrees from the equator. In the Northern hemisphere, 40 degrees draws a line between New York city and Beijing. A recent meta-analysis found consistently that sunscreen users above 40 degrees are at a higher risk of melanoma than people who don't use sunscreen, even when differences in skin color are taken into account. Wearing sunscreen decreased melanoma risk in studies closer to the equator. It sounds confusing, but it makes sense once you know a little bit more about UV rays, sunscreen and the biology of melanoma.

The UV light that reaches the Earth's surface is composed of UVA (longer) and UVB (shorter) wavelengths. UVB causes sunburn, while they both cause tanning. Sunscreen blocks UVB, preventing burns, but most brands only weakly block UVA. Sunscreen allows a person to spend more time in the sun than they would otherwise, and attenuates tanning. Tanning is a protective response (among several) by the skin that protects it against both UVA and UVB. Burning is a protective response that tells you to get out of the sun. The result of diminishing both is that sunblock tends to increase a person's exposure to UVA rays.

It turns out that UVA rays are more closely associated with melanoma than UVB rays, and typical sunscreen fails to prevent melanoma in laboratory animals. It's also worth mentioning that sunscreen does prevent more common (and less lethal) types of skin cancer.

Modern tanning beds produce a lot of UVA and not much UVB, in an attempt to deliver the maximum tan without causing a burn. Putting on sunscreen essentially does the same thing: gives you a large dose of UVA without much UVB.

The authors of the meta-analysis suggest an explanation for the fact that the association changes at 40 degrees of latitude: populations further from the equator tend to have lighter skin. Melanin blocks UVA very effectively, and the pre-tan melanin of someone with olive skin is enough to block most of the UVA that sunscreen lets through. The fair-skinned among us don't have that luxury, so our melanocytes get bombarded by UVA, leading to melanoma. This may explain the incredible rise in melanoma incidence in the US in the last 35 years, as people have also increased the use of sunscreen. It may also have to do with tanning beds, since melanoma incidence has risen particularly in women.

In my opinion, the best way to treat your skin is to tan gradually, without burning. Use clothing and a wide-brimmed hat if you think you'll be in the sun past your burn threshold. If you want to use sunscreen, make sure it blocks UVA effectively. Don't rely on the manufacturer's word; look at the ingredients list. It should contain at least one of the following: titanium dioxide, zinc oxide, avobenzone (Parsol 1789), Mexoryl SX (Tinosorb). It's best if it's also paraben-free.

Fortunately, as an external cancer, melanoma is easy to diagnose. If caught early, it can be removed without any trouble. If caught a bit later, surgeons may have to remove lymph nodes, which makes your face look like John McCain's. Later than that and you're probably a goner. If you have any questions about a growth, especially one with irregular borders that's getting larger, ask your doctor about it immediately!

Princess Health and Grains and Human Evolution.Princessiccia

Princess Health and Grains and Human Evolution.Princessiccia

archaeology diet gluten

Gusty 18:38 Add Comment

[Update 8/2011: as I've learned more about human genetics and evolution, I've come to appreciate that many Europeans actually descend from early adopters of agriculture more than they descend from the hunter-gatherers that previously occupied Europe.  Also, 10,000 years has been long enough for significant genetic adaptation.  Read The 10,000 Year Explosion for more information].

You've heard me say that I believe grains aren't an ideal food for humans. Part of the reason rests on the assertion that we have not been eating grains for long enough to have adapted to them. In this post, I'll go over what I know about the human diet before and after agriculture, and the timeline of our shift to a grain-based diet. I'm not an archaeologist so I won't claim that all these numbers are exact, but I think they are close enough to make my point.

As hunter-gatherers, we ate some combination of the following: land mammals (including organs, fat and marrow), cooked tubers, seafood (fish, mammals, shellfish, seaweed), eggs, nuts, fruit, honey, "vegetables" (stems, leaves, etc.), mushrooms, assorted land animals, birds and insects. The proportion of each food varied widely between groups and even seasons. This is pretty much what we've been living on since we evolved as a species, and even before, for a total of 1.5 million years or so (this number is controversial but is supported by multiple lines of evidence). There are minor exceptions, including the use of wild grains in a few areas, but for the most part, that's it.

The first evidence of a calorically important domesticated crop I'm aware of was about 11,500 years ago in the fertile crescent. They were cultivating an early ancestor of wheat called emmer. Other grains popped up independently in what is now China (rice; ~10,000 years ago), and central America (corn; ~9,000 years ago). That's why people say humans have been eating grains for about 10,000 years.

The story is more complicated than the dates suggest, however. Although wheat had its origin 11,500 years ago, it didn't become widespread in Western Europe for another 4,500 years. So if you're of European descent, your ancestors have been eating grains for roughly 7,000 years. Corn was domesticated 9,000 years ago, but according to the carbon ratios of human teeth, it didn't become a major source of calories until about 1,200 years ago! Many American groups did not adopt a grain-based diet until 100-300 years ago, and in a few cases they still have not. If you are of African descent, your ancestors have been eating grains for 9,000 to 0 years, depending on your heritage. The change to grains was accompanied by a marked decrease in dental health that shows up clearly in the archaeological record.

Practically every plant food contains some kind of toxin, but grains produce a number of nasty ones that humans are not well adapted to. Grains contain a large amount of phytic acid for example, which strongly inhibits the absorption of a number of important minerals. Tubers, which were our main carbohydrate source for about 1.5 million years before agriculture, contain less of it. This may have been a major reason why stature decreased when humans adopted grain-based agriculture. There are a number of toxins that occur in grains but not in tubers, such as certain heat-resistant lectins.

Non-industrial cultures often treated their seeds, including grains, differently than we do today. They used soaking, sprouting and long fermentation to decrease the amount of toxins found in grains, making them more nutritious and digestible. Most grain staples are not treated in this way today, and so we bear the brunt of their toxins even more than our ancestors did.

From an evolutionary standpoint, even 11,500 years is the blink of an eye. Add to that the fact that many people descend from groups that have been eating grains for far less time than that, and you begin to see the problem. There is no doubt that we have begun adapting genetically to grains. All you have to do to understand this is look back at the archaeological record, to see the severe selective pressure (read: disease) that grains placed on its early adopters. But the question is, have we had time to adapt sufficiently to make it a healthy food? I would argue the answer is no.

There are a few genetic adaptations I'm aware of that might pertain to grains: the duplication of the salivary amylase gene, and polymorphisms in the angiotensin-converting enzyme (ACE) and apolipoprotein B genes. Some groups duplicated a gene that secretes the enzyme amylase into the saliva, increasing its production. Amylase breaks down starch, indicating a possible increase in its consumption. The problem is that we were getting starch from tubers before we got it from grains, so it doesn't really argue for either side in my opinion. The ACE and apolipoprotein B genes may be more pertinent, because they relate to blood pressure and LDL cholesterol. Blood pressure and blood cholesterol are both factors that respond well to low-carbohydrate (and thus low-grain) diets, suggesting that the polymorphisms may be a protective adaptation against the cardiovascular effects of grains.

The fact that up to 1% of people of European descent may have full-blown celiac disease attests to the fact that 7,000 years have not been enough time to fully adapt to wheat on a population level. Add to that the fact that nearly half of genetic Europeans carry genes that are associated with celiac, and you can see that we haven't been weeded out thoroughly enough to tolerate wheat, the oldest grain!

Based on my reading, discussions and observations, I believe that rice is the least problematic grain, wheat is the worst, and everything else is somewhere in between. If you want to eat grains, it's best to soak, sprout or ferment them. This activates enzymes that break down most of the toxins. You can soak rice, barley and other grains overnight before cooking them. Sourdough bread is better than normal white bread. Unfermented, unsprouted whole wheat bread may actually be the worst of all. 

Princess Health and Another China Tidbit.Princessiccia

Princess Health and Another China Tidbit.Princessiccia

diet gluten hyperphagia overweight

Gusty 18:05 Add Comment

A final note about the Chinese study in the previous post: the overweight vegetable-eaters (read: wheat eaters) exercised more than their non-vegetable-eating, thin neighbors. So although their average calorie intake was a bit higher, their expenditure was as well. 

Although I speculated in the last post that affluent people might be eating more wheat and fresh vegetables, the data don't support that. Participants with the highest income level actually adhered to the wheat and vegetable-rich pattern the least, while low-income participants were most likely to eat this way.

Interestingly, education showed a (weaker) trend in the opposite direction. More educated participants were more likely to eat the wheat-vegetable pattern, while the opposite was true of less educated participants. Thus, it looks like wheat makes people more educated. Just kidding, that's exactly the logic we have to avoid when interpreting this type of study!

Princess Health and Wheat in China.Princessiccia

Princess Health and Wheat in China.Princessiccia

diet gluten hyperphagia overweight

Gusty 17:11 Add Comment

Dr. Michael Eades linked to an interesting study yesterday on his Health and Nutrition blog. It's entitled "Vegetable-Rich Food Pattern is Related to Obesity in China."

It's one of these epidemiological studies where they try to divide subjects into different categories of eating patterns and see how health problems associate with each one. They identified four patterns: the 'macho' diet high in meat and alcohol; the 'traditional' diet high in rice and vegetables; the 'sweet tooth' pattern high in cake, dairy and various drinks; and the 'vegetable rich' diet high in wheat, vegetables, fruit and tofu. The only pattern that associated with obesity was the vegetable-rich diet. The 25% of people eating closest to the vegetable-rich pattern were more than twice as likely to be obese as the 25% adhering the least.

The authors of the paper try to blame the increased obesity on a higher intake of vegetable oil from stir-frying the vegetables, but that explanation is misleading. A cursory glance at table 3 reveals that the vegetable-eaters weren't eating any more fat than their thinner neighbors. Dr. Eades suggests that their higher carbohydrate intake (+10%) was partially responsible for the weight gain, but I wasn't satisfied with that explanation so I took a closer look.  Dr. Eades also pointed to their higher calorie intake (+120 kcal/day), which makes sense to me.

One of the most striking elements of the 'vegetable-rich' food pattern is its replacement of rice with wheat flour. The 25% of the study population that adhered the least to the vegetable-rich food pattern ate 7.3 times more rice than wheat, whereas the 25% sticking most closely to the vegetable-rich pattern ate 1.2 times more wheat than rice! In other words, wheat flour rather than rice was their single largest source of calories. This association was much stronger than the increase in vegetable consumption itself!

All of a sudden, the data make more sense. Wheat seems to associate with health problems in many contexts. Perhaps the reason we don't see the same type of association in American epidemiological studies is that everyone eats wheat. Only in a culture that has a true diversity of diet can you find a robust association like this. The replacement of rice with wheat may have caused the increase in calorie intake as well. Clinical trials of low-carbohydrate diets as well as 'paleolithic diets' have shown good metabolic outcomes from wheat avoidance, although one can't be sure what role wheat plays from those data.

I don't think the vegetables had anything to do with the weight gain, they were just incidentally associated with wheat consumption. But I do think these data are difficult to reconcile with the idea that vegetables protect against overweight.

Princess Health and BLOGSCAN - Continuing Investigation of Orthopods' Financial Relationships with Prosthetic Joint Manufacturers. Princessiccia

Princess Health and BLOGSCAN - Continuing Investigation of Orthopods' Financial Relationships with Prosthetic Joint Manufacturers. Princessiccia

conflicts of interest medical devices orthopedic surgeons

Gusty 13:49 Add Comment

On the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody expanded his focus a bit to include medical device companies. He posted about the ongoing investigations of orthopedic surgeons' financial relationships to the manufacturers of prosthetic joints. He cited an unnamed senior general surgeon who "did not think that anywhere near as much real 'consulting' ever got done as cash flowed into docs' pockets." This story keeps bubbling just below the surface. Stay tuned, as I suspect there will be more developments.

Princess Health and BLOGSCAN - Imperial Pharmaceutical CEOs. Princessiccia

Princess Health and BLOGSCAN - Imperial Pharmaceutical CEOs. Princessiccia

Bristol-Myers-Squibb Cephalon imperial CEO pharmaceuticals power elite

Gusty 13:38 Add Comment

On the PharmaLot blog, Ed Silverman has two posts about how pharmaceutical executives continue to rake in humongous compensation whose magnitude seems unrelated to their performance or the performance of their companies. The CEO of Cephalon got more than $15.8 million, including the value of stock options, while the company is dealing with an Federal Trade Commission lawsuit which contends the company blocked sales of a generic competitor, and despite settling a suit about off-label marketing (see post here.) The CEO of Bristol-Myers-Squibb got $13.5 million after the company's stock price fell, the company took a charge for losses on sub-prime mortgages, and several top financial officers left (see post here.) Again, as we noted earlier, imperial CEOs seem rampant in health care organizations.

Princess Health and Who Was Responsible for the Purity of Baxter International's Heparin?. Princessiccia

Princess Health and Who Was Responsible for the Purity of Baxter International's Heparin?. Princessiccia

Baxter biotechnology heparin Mismanagement outsourcing pharmaceuticals

Gusty 11:30 Add Comment

We have posted several times, most recently here and here, about the tragic case of suddenly allergenic heparin. Although heparin, an intravenous biologic anti-coagulant, has been in use for over 70 years, serious allergic reactions to it had heretofore been rare. Starting late last year, hundreds of such reactions, and now 21 deaths were reported in the US after intravenous heparin infusions.

All the heparin related to these events was made by Baxter International. We then learned that although the heparin carried the Baxter label, it was not really made by Baxter. In fact, the company had outsourced production of the active ingredient to a long, and ultimately mysterious supply chain. Baxter got the active ingredient from a US company, Scientific Protein Laboratories LLC, which in turn obtained it from a factory in China operated by Changzhou SPL, which in turn was owned by Scientific Protein Laboratories and by Changzhou Techpool Pharmaceutical Co. Changzhou SPL, in turn, got it from several consolidators or wholesalers, who in turn got it from numerous small, unidentified "workshops," which seemed to produce the product in often primitive and unsanitary conditions. None of the stops in the Chinese supply chain had apparently been inspected by the US Food and Drug Administration nor its Chinese counterpart. Most recently, we found out that the Baxter International labelled heparin was contaminated with over-sulfated chondroitin sulfate, a substance not found in nature, but which mimics heparin according to the simple laboratory tests used in the Chinese facilities to check incoming heparin. (See post here.)

It is not clear whether Baxter International or Scientific Protein Laboratories had inspected most of the steps in the supply chain, or even knew what went on there. The Baxter and Scientific Protein Laboratories CEOs did not seem aware of where they got the heparin on which the Baxter International label was eventually affixed. But one report in the New York Times alleged that Scientific Protein Laboratories would not pay enough for heparin to satisfy any sources other than the small "workshops."

By the end of this week, it became clear that the counterfeit ingredient was added to the heparin in China. Per Bloomberg,

The contamination was present in the powdered raw heparin purchased by Scientific Protein's plant in China, said Robert Rhoades, a pharmaceutical consultant with Becker & Associates in Washington, speaking for Scientific Protein. The company was unaware of the contamination at the time because it wasn't detected in tests Scientific Protein conducted on the powder provided by suppliers, he said.

Scientific Protein purchased raw heparin from consolidators and refined it further before sending it to Baxter, which uses the ingredient to make the finished drug, Rhoades said. The consolidators obtained the ingredients from workshops in China, he said.

The contaminant 'was very likely introduced at the workshop or consolidator level,' Norbert Riedel, Baxter's corporate vice president and chief scientific officer, has said.

Nonetheless, a number of experts suggested that there was reason not be complacent about drugs made in China. A Washington Post article noted that it was well known that Chinese manufacturers were liable to supply dodgy drugs,

Although the contaminated heparin is the largest and highest-profile instance of tainted prescription drugs made in China, it is not the first. In the late 1990s, a spike in deaths associated with the intravenous antibiotic gentamicin was linked to China-based Long March Pharmaceuticals. Although no definitive link was ever established, tests by German researchers later found a wide range in quality and effectiveness in what were supposed to be uniform dosages of the drug, leading them to write that 'it was assumed' the deaths 'were related to faulty manufacture.'

The Post quoted former US Food and Drug Administration (FDA) official William Hubbard,

The history of some of these developing countries in terms of substituting or counterfeiting concerns is a long and well-documented one....

USA Today quoted former FDA Commissioner David Kessler saying that

the news shouldn't come as a surprise: China is 'as close to an unregulated environment as you can get.' In fact, it's a lot like the USA was in 1906, he says �'that's why we developed an FDA.'

Furthermore, one expert argued that Baxter International was ultimately responsible for the drug that it sold, per the Chicago Tribune,

The presence of a foreign ingredient raises new questions about Baxter's oversight because a lack of record-keeping at the China plant makes it more difficult for Baxter and government inspectors to trace the origin of the raw material for Baxter's product.

'Where are the controls here? What is the process here?' asked Carl Nielsen, who was the FDA's director of import operations and policy before leaving the agency to form a consulting firm in 2005.

'Ultimately, Baxter is the most responsible' for monitoring the quality of products that move through the company's pipeline, Nielsen said.

Yet Baxter International executives have not exactly been jumping forward to claim responsibility. In a letter, again to the Chicago Tribune, Peter J Arduini, President, Medication Delivery, for Baxter International seemed to be deflecting responsibility towards Scientific Protein Laboratories and the FDA, while asserting Baxter did all it could do.

Regarding the issue of active pharmaceutical ingredient that originated in China, Baxter's API supplier for heparin is in fact a Wisconsin-based company, Scientific Protein Laboratories, with whom Baxter and its predecessor in this business has worked for more than 30 years. SPL had been procuring heparin raw material from China for more than 10 years and opened a location in Changzhou, China, in 2004. Baxter worked with the U.S. Food and Drug Administration to obtain the appropriate approvals to work with this facility. For the API we receive from SPL, and for the API we receive from all our suppliers, Baxter performs quality testing of all incoming materials above and beyond what's required, to ensure that incoming API is what our suppliers claim it to be. Unfortunately, as the FDA has said, the problematic heparin API could not have been detected by the testing required of and done by any heparin manufacturer.

Previously Baxter International's CEO, Robert L Parkinson Jr, had dodged responsibility for the supply chain that provided the heparin to Scientific Protein Research's Changzhou facility, as we posted here, and as originally reported in the Chicago Tribune,

Baxter International Inc. does not monitor its supply chain to the extent that it would know that a supplier in China was never inspected before it began shipment of the blood-thinning drug heparin, which is linked to more than 300 illnesses in the U.S., the company's chief executive said Wednesday.

Baxter contracted with a Wisconsin supplier, Scientific Protein Laboratories, and not with that company's Chinese affiliate, Baxter CEO Robert Parkinson said Wednesday in his first interview since the heparin problems surfaced.

'It's not unusual for us not to know that the FDA hasn't inspected a supplier to a supplier,' Parkinson said.

Yet if Baxter International is not responsible for the production of drugs that carry its name, who is? If Baxter International's executives are not responsible for how the drugs it sells are manufactured, who should be?

In an ironic juxtaposition, a small and little noticed news item last week declared that Robert Parkinson received $16,600,000 in compensation in 2007, a 30.5% increase from 2006. In fact, the company's 2008 proxy statement suggests even greater total compensation in 2007, $17,580,718. And Mr Arduini's 2007 compensation was reported to be $2,438,642.

The usual justification for compensation at this level is the brilliance of and great responsibilities borne by the executives who receive it. But, if Baxter International's executives will not take responsibility for their products and how they are made, what again is the justification for paying them the big bucks?

So the case of the contaminated heparin becomes another reason to question the imperial nature of the current leadership of health care organizations.