Oh, the tangled web we weave, when science we manipulate in order for profits to achieve...

Oh, this story just won't go away.

Years ago, when olanzapine (Zyprexa) was fairly new to the market, my colleagues started commenting that they noticed huge weight gains (like 40-50 pounds) in short time intervals (like a month). No matter where we attempted to get information, Lilly, this drug's manufacturer, insisted that this drug did not increase weight gain.

I had the opportunity to meet one of Lilly's lead marketing guys at a national conference. We exchanged cards and when I got home I emailed him with a proposal that the team of nutritionists I was training in the area of psychotropic medications and hormone imbalances, work with Lilly to create a diabetes management educational program targeted specifically at psychiatrists, who were not specialized in this area but who appeared to need support in order to use these new medications in safe and appropriate ways.

I received an email in return, carbon copied to quite a few people at Lilly, stating that "weight gain on our medication is an unscientific rumor". (I now call this correspondence my "60 Minutes E-mail").

It wasn't 6 months before Lilly was required to put a black box warning on this very medication regarding its potential to cause diabetes. Apparently the timing of my original email struck a raw nerve.

What really bothered me about this whole situation was at the very time Lilly was insisting that that this drug did not cause weight gain, they were marketing it to eating disorder specialists as a treatment option for anorexia nervosa.

Yes, you heard me correctly. Lilly apparently wanted us to believe that the drug doesn't cause weight gain if you use it in people who don't want to gain weight, but it is very effective in causing weight gain in people who desperately need to gain weight.

Fast forward to last Friday. I'm scanning new research abstracts in Pub Med and right next to each other I see these two titles:

Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial.

Olanzapine (LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine), but not the novel atypical antipsychotic ST2472 (9-piperazin-1-ylpyrrolo[2,1-b][1,3]benzothiazepine), chronic administration induces weight gain, hyperphagia, and metabolic dysregulation in mice.

There is also, in Pub Med, research to suggest that this medication may trigger binge eating disorder.

So apparently, the newest, quickest way to cure anorexia is to replace it with another eating disorder. Never mind that it creates hormone imbalances that are strongly documented and have mandated a warning be placed on this drug.

I thought when we helped people with anorexia, they were supposed to be healthy in all respects. Not just normal weight with a risk of developing diabetes. Which, by the way, is starting to be associated with Alzheimer's disease.

Insert huge, frustrated, sigh...

Bissada H, Tasca GA, Barber AM, Bradwejn J. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2008 Oct;165(10):1281-8. Epub 2008 Jun 16.

Coccurello R, Caprioli A, Conti R, Ghirardi O, Borsini F, Carminati P, Moles A. Olanzapine (LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine), but not the novel atypical antipsychotic ST2472 (9-piperazin-1-ylpyrrolo[2,1-b][1,3]benzothiazepine), chronic administration induces weight gain, hyperphagia, and metabolic dysregulation in mice. J Pharmacol Exp Ther. 2008 Sep;326(3):905-11. Epub 2008 Jun 20.

Theisen FM, Linden A, König IR, Martin M, Remschmidt H, Hebebrand J. Spectrum of binge eating symptomatology in patients treated with clozapine and olanzapine. J Neural Transm. 2003 Jan;110(1):111-21.

Gebhardt S, Haberhausen M, Krieg JC, Remschmidt H, Heinzel-Gutenbrunner M, Hebebrand J, Theisen FM. Clozapine/olanzapine-induced recurrence or deterioration of binge eating-related eating disorders. J Neural Transm. 2007;114(8):1091-5. Epub 2007 Mar 20.

Kluge M, Schuld A, Himmerich H, Dalal M, Schacht A, Wehmeier PM, Hinze-Selch D, Kraus T, Dittmann RW, Pollmächer T. Clozapine and olanzapine are associated with food craving and binge eating: results from a randomized double-blind study. J Clin Psychopharmacol. 2007 Dec;27(6):662-6.

Do we really need to do this kind of stuff in the name of science?

I read scientific research an average of 2 hours a day. I see some pretty strange things. Today I encountered the horrible.

Mexican scientists interested in whether or not melatonin could lessen the damaging effects of a caustic burn, induced such a burn in the esophagi (plural for esophagus) of rats. Their rationale was that caustic ingestion (you know, things like drinking Liquid Plumr) is a serious life-threatening event in children.

I don't understand why, since melatonin is a naturally occurring substance, they couldn't just do the research using children who had already, accidentally, ingested something caustic? Since the purpose of the research is supposedly to help these children, wouldn't the research be best conducted on the population it is intended to help?

This is just cruel. I almost didn't post this because I didn't want to reward this kind of sadistic thinking by giving it attention. But at some point you just have to stand up and say, "That's just wrong."

Oh, by the way, the melatonin worked. So while these guys were busy in their lab burning rat throats in order to get a publication, Mexican children who could have benefited from being subjects in the study...sat in the hospital with burnt throats and no melatonin to help them. Go figure.

Larios-Arceo F, Ortiz GG, Huerta M, Leal-Cortés C, Saldaña JA, Bitzer-Quintero OK, Rodríguez-Reynoso S. Protective effects of melatonin against caustic esophageal burn injury in rats. J Pineal Res. 2008 Sep;45(2):219-23. Epub 2008 Mar 26.

Monkeys with no memories and the marijuana munchies

Endocannabinoids are chemicals we make that are important in many functions, including cognitive thought, and memory. When our internal endocannabinoid levels are low, we also start to crave sugar. (THC, the active ingredient in marijuana, is also a cannabinoid, and using it messes with our cannabinoid system, giving us the munchies).

In this study, endocannabinoid levels were evaluated in the prefrontal cortex area of 23 pairs of brain cadavers of people with schizophrenia and normal age and gender matched comparisons. Messenger RNA levels for endocannabinoid production were lower in the schizophrenic brains.

Eighteen brains of macaque monkeys who had been exposed long-term to one of two antipsychotics, haloperidol (Haldol) or olanzapine (Zyprexa), were compared to brains that had never been exposed to these medications. There was no significant difference in their endocannabinoid levels. So even though the medication was helping some aspect of the schizophrenia, it was not correcting the endocannabinoid imbalance.

That might provide one reason why it might be hard for schizophrenics to stay compliant with their medication--they're not being given a medication that helps their brains remember to take it.

As a nutritionist, I also see an important "next study". Knowing that omega-3 fatty acids DO improve cognition and memory, I wonder what would happen if that supplementation was added to the protocol?

It also explains why these clients have such an appetite for sweets, and the kind of foods that further degrade the brain. It's coming from a pretty entrenched biological mechanism.

Eggan SM, Hashimoto T, Lewis DA. Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch Gen Psychiatry. 2008 Jul;65(7):772-84.

OK, I managed to keep a straight face until now, which I wanted to do since schizophrenia is an entirely serious topic and people with the disease deserve my respect. Completely. But do you know how hard it was to word this study without using the distracting phrase "monkey brain"? I figured this guy must have been a subject, given his predilection for popsicles.

Fish and dementia

I've talked a lot about how fish develops brain power. It also helps you hang onto the brain power you have! In a French study, 1214 seniors without dementia were followed for 4 years. During that time, 65 of them developed dementia. It was found that the higher the person's eicosapentaenoic acid (EPA) level, the lower the risk of dementia. Factors that could have explained this trend that were factored out included: age, education, diabetes, and vitamin E levels. EPA appeared to be a more significant determinant in this population than did the "other" fish oil, docosahexaenoic acid, or DHA.

When individuals also had depression, it appears as total fatty acid ratios also became important. High ratios of the omega-6 fatty acids to omega-3 fatty acids were also important in risk determination.

One thing to take away from this study: Omega-3's are important for preserving brain integrity. Secondly, balancing the right kind of fats and limiting the potentially destructive ones (omega-6's, if you've been reading this blog that means the "S" and "C" oils), is important for managing mood and preventing depression.

Samieri C, Féart C, Letenneur L, Dartigues JF, Pérès K, Auriacombe S, Peuchant E, Delcourt C, Barberger-Gateau P. Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk. Am J Clin Nutr. 2008 Sep;88(3):714-21.

Trans fat information

Yes, I've been a little quiet lately. I've been traveling, and also ramping up to re-launch my newsletter, After the Diet. This next issue is about food policy, which I really want to get out before the election.

Don't fret, I did my best to be nonpartisan! The goal was mainly to illustrate how the things we believe about food and the foods that show up in our food supply are related to deals cut on Capitol Hill. I do my best to stay right down the middle. My obligation is to help anyone who can benefit from my expertise, since diabetes, infertility, depression, you name it, affect Democrats, Republicans, Libertarians, and Independents.

It matters not to me HOW you vote, it matters THAT you vote, and that when you do, your vote is informed.

So I researched some issues related to foods and put them together in a newsletter.

The graphic you see is a handout, included in that newsletter, that I developed on trans-fats, since they've recently been making a lot of news and I see clients misusing this information since they don't understand it.

If you're interested in any of the following:
--why wild salmon isn't really wild
--why the United States sued Mexico to import high-fructose corn syrup
--how flooding in Iowa may be raising the price of shrimp
--why catfish is not so easy to find in your grocery store
--what food-related legislation was actually co-sponsored by (!) John McCain and
John Kerry
--what FDA warning is potentially reducing the IQ of babies
--what one simple change Americans could make to collectively save $18,630,000,000
then you might be interested in subscribing to my newsletter.

I'm already working on the next edition, which will cover the following topics:

Melatonin: The Ultimate Antioxidant?

Dietary Aspects of Melatonin Balance

Sleep, Weight, Insulin Resistance, and Aging

Why Do Pilots Have Shortened Lifespans?

Is It Attention Deficit Disorder? Or Is It Sleep Deprivation?

It's a really fun publication and I'd love to have you subscribe!

I promise, once I get this issue out, there's lots and lots to blog about.

Stay tuned!

The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment:

In my last post, I suggested that despite the findings of one study, it was still a good idea to supplement omega-3 fatty acids in the diet. Here is one study supporting my argument.

Forty-six seniors with mild to moderate Alzheimer's disease were given either a dose of omega-3's of 1.8 grams per day (roughly equivalent to what was provided in the previously mentioned study) or placebo. A 24-week, randomized, double-blind placebo-controlled study was carried out to test the feasibility of using omega-3 polyunsaturated fatty acids (PUFAs) monotherapy in people with cognitive impairment and to explore its effects on cognitive function and general clinical condition in these participants. Seventy-six participants completed the study. Those who received the omega-3's showed better improvement on a clinician-based assessment of symptoms. The change was more significant in those individuals with mild cognitive impairment than it was in those diagnosed with Alzheimer's disease.

The changes were more significant, also, in persons with higher concentrations of eicosapentaenoic acid (EPA) in their red blood cells.

And, as I suggested, study design is an important determinant of outcome. In the words of the researchers, "Further studies should be considered with a larger-sample size, diet registration, higher dosages, comparisons between different combinations of PUFAs, and greater homogeneity of participants, especially those with mild Alzheimer's disease and mild cognitive impairment."

I am excited to see what studies like this teach us about minimizing the devastating effects of diseases of aging, such as dementia and Alzheimer's disease!

Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, Stewart R, Huang SY. The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1538-44. Epub 2008 May 25.

Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial.

We hear all the time that fish oil is good for mood. So why did this study here not come to that conclusion?

302 seniors (independently living) were divided into 3 groups. The first group was dosed 1800 daily milligrams of EPA and DHA, the second group 400 milligrams, and the third group received placebo capsules. Before being given the capsules, and 13 and 26 weeks into the study, plasma concentrations of EPA and DHA as well as responses to several psychological tests were measured. Even though the fish oil significantly increased EPA and DHA concentration in the two dosed groups (by 238% in the high dose and 51% in the low dose), responses to the questionnaires were not significantly different. Why is that? There are probably several reasons.

1. Brain function is about a lot more than just omega-3 balance. Independently living seniors are likely to be eating an overall diet that is deficient in several nutrients. It would have been interesting to see a baseline blood test of other nutrient levels to see if overall nutritional status was correlated with test scores and EPA/DHA response.
2. The background diet of these seniors was not measured, or if it was, it was not reported. If, which is common because of convenience, the group as a whole was eating a lot of pre-prepared and packaged food, the ratio of pro-inflammatory oils to dietary omega-3 content may affect the outcome of the study.

It doesn't mean that just because there was not a mood-based response to these oils that they weren't beneficial. If levels of omega-3's increased dramatically, they most certainly were reducing cardiovascular risk, preventing the development of dementia and Alzheimer's, and improving bone health, to mention a few.

I just wish these researchers would understand the importance of controlling diet in any study that investigates the usefulness of an isolated supplement. Not only will it provide more significant results, it will keep people from mistakenly assuming that a certain nutrient is not of benefit when it actually is.

van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Hoefnagels WH, Beekman AT, de Groot LC. Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2008 Sep;88(3):706-13.