You’ve probably noticed that I haven’t been able to write as much lately for the blog. I’ve been incredibly busy with my private practice, launching the Paleo Detox program, preparing and delivering talks locally, developing new content like ongoing class series and an eBook, and of course continuing my research on various topics.

I’ve got one more article to write for the series on diabesity. I’ll discuss what I believe to be the most effective form of exercise for restoring glucose tolerance and insulin sensitivity. I hope to get to that this weekend.

After that, I’ll be sending out a survey to get your input on the next series, as well as several other topics related to the blog and various projects I’ve got in the works.

I hope to get back to a more regular writing schedule at some point, but with everything going on it may take a while. In the meantime, I may try out some new formats, like posting a brief summary of articles from around the web that I’ve found interesting during the week.

Here are a few from this week.

Why Is My Cholesterol So High On This Diet?

In this article, Chris Masterjohn explains why some people see their cholesterol go up (often temporarily) when they switch to a nutrient-dense, whole-foods based diet. His theory, which is plausible from a physiological standpoint, is that the temporary cholesterol elevation is occurs because these folks are curing themselves of fatty liver disease.

In any event, we know that total and LDL cholesterol are weakly correlated with heart disease, so I’m never concerned when I see people’s cholesterol go up on a paleo or nutrient-dense diet. It’s expected. Especially when their HDL goes up and their triglycerides go down, which is the typical response.

Huge Metastudy: “Non Diabetic” Blood Sugars Cause “Diabetic” Retionopathy

Throughout my series on diabesity, I’ve presented evidence that blood sugar levels considered to be “normal” by mainstream standards are anything but, and that they can lead to complications like retinopathy and peripheral neuropathy.

Jenny Ruhl blogged today about a recently published meta-analysis that confirms this once again. In the study, blood sugar levels of 117 mg/dL or above, and an A1c of 6.3 or above (both below current limits) significantly increased the risk of retinopathy. But, as Jenny points out, the safe limits are lower still, because retinopathy is one of the last complications of diabetes to appear. Heart disease risk increases as post-meal blood sugars rise above 155 mg/dL, and increases in a straight line with A1c above 4.7, becoming quite significant as it rises above 6.

Grasse Based Health: Food For Thought

In this video, Peter Ballerstedt argues that animal protein and animal fat are not only superior to grains for human health, but also more sustainable from an agricultural and ecological perspective.

The presentation is quite dry, but the information is solid and it’s definitely worth watching.

Excerpted from Sciencedaily.com, 9/4/08

In an effort to better understand how chronic stress affects the human body, researchers at the Yerkes National Primate Research Center and the Department of Psychiatry and Behavioral Sciences, Emory University, have created an animal model that shows how chronic stress affects behavior, physiology and reproduction.

According to lead researcher Mark Wilson, PhD, chief of the Division of Psychobiology at Yerkes, “Chronic stress can lead to a number of behavioral changes and physical health problems, including anxiety, depression and infertility.”

Via the animal model, the researchers found corticotropin releasing factor (CRF) is a key neurohormone involved in stress response. Wilson explains, “CRF is located in several different brain regions, serving different functions. Its release is important for our ability to adapt to every day stressors and to maintain our physical and emotional health.”

In response to stress, CRF levels rise; CRF levels decrease when the stressor no longer is present. Chronic stress, however, increases the length and volume of expression of CRF in areas of the brain associated with fear and emotion, including the amygdala. Such chronic stress changes the body’s response, and the resulting increased expression of CRF is thought to be the cause of such health-related stress problems including anxiety, depression and infertility.

I’d like to thank everyone for their comments, both online and “offline” about my recent “Placebos as Effective as Antidepressants” article. Some very good questions were raised in a comment from Stephan, author of the highly recommended Whole Health Blog that I would like to address in today’s article.

The tricky thing about doing scientific research, as I explained in last week’s article, is that conflicts of interest between doctors, researchers and pharmaceutical companies have become so prevalent that the results of even studies published in prominent, peer-reviewed journals cannot be taken at face value.

One must ask: was the study designed properly? Do the author’s conclusions match their own data? Have the authors reported all of the relevant results? Who funded the study, and what role did they have in choosing the subjects, overseeing the methodology and publishing the results?

When looking at a body of research, one must also consider whether there are unpublished studies on the topic and what the effect of those studies might be. This is particularly true in the case of antidepressants, where it has been estimated that approximately 23% of studies have not been published. Why? Because those studies had even less favorable results than those studies that have been published, and the drug companies who paid for them are under no legal obligation (currently – hopefully this might change in the future) to publish study results.

With that in mind, let’s consider Stephan’s comment and each of the points he brings up in turn:

I want to thank Stephan again for his comment and for raising these important issues.

Let’s start with the parts that I agree with. Certainly, depression has become so broad a term that some have argued that it is an essentially meaningless clinical designation. Unlike other conditions that have measurable physiological markers, people that are diagnosed as depressed do not usually have any features that categorically distinguish them from other people. The sorts of problems that are diagnosed as depression can very considerably depending upon which diagnostic criteria are used, the interpretation of those criteria, and cultural and professional attitudes.

In their book The Loss of Sadness, Horwitz and Wakefield point out that the diagnosis of depression has now come to include transient and completely appropriate responses to life such as sadness after the passing of a loved one, disappointment after the loss of a job or anxiety about financial troubles. They argue, very convincingly, that the DSM IV criteria for depression do not adequately distinguish between what they call “normal sadness” and depression, and the result has been the almost complete medicalization of our emotional response to life. I will be writing an article on this very soon, as I believe it’s a critical perspective to understand in our exploration of depression and antidepressants.

Secondly, I certainly cannot argue with the statement that “antidepressants work for some people”. However, the important questions to ask in relation to that statement are:

• Why do antidepressants work
• How do antidepressants work?
• Whom do they work for?

Why are these questions important? Because if it turns out that antidepressants do not have any specific drug effects (raising serotonin, for example), and work only because people expect or desire them to work (like placebos), or because of non-specific drug effects (such as sedation or stimulation), then the logic behind prescribing antidepressants at all becomes quite tenuous to say the least – especially when their side effects and risks are taken into consideration.

Now let’s consider each point in turn.

What Stephan says about the dangers of meta-analysis are true. However, the same danger applies to overestimating the efficacy of antidepressants. There may be some people who are “responders” who have a response to the drug that is significantly higher than placebo; however, there may also be “nonresponders” whose response to the drug was significantly lower than placebo. There is no indication that antidepressants work on a particular subset of people, and no one has identified who this subset is and why they are helped by antidepressants when others are not.

Kirsch’s analysis that antidepressants do not have a clinically meaningful advantage over placebo (“The Emperor’s New Drugs“) has been almost universally accepted within the scientific community. Kirsch’s and his colleagues invoked the Freedom of Information Act to obtain access to the FDA database of controlled trials used in the initial approval for the most popular antidepressants. According to researcher David O. Antonuccio in his article “Antidepressants: A Triumph of Marketing Over Science?“, it is difficult to imagine a database that would offer a more fair opportunity to evaluate the efficacy of antidepressants.

The fact that Kirsch found that antidepressants were no more effective than placebo is surprising, in a way, because these results come from studies that were underwritten and designed by the drug companies themselves under conditions most favorable to the active drug condition. In other words, the deck was stacked from the start in favor of the drugs, and they still didn’t come out ahead.

Since a drug must be shown to be superior to placebo in order to be approved, placebo effects are incredibly annoying to drug companies and they do everything they can to minimize the impact of placebo in their studies. The fact that the FDA allows them to use these techniques is, in my mind, blatant corruption. Consider the following methods used in the studies Kirsch analyzed (and most studies, for that matter):

1. Placebo washout period: During the first two weeks of the study, everyone is on a placebo. The subjects that respond best to placebo are eliminated from the study. This potentially removes both antidepressant nonresponders (i.e. those that were on an antidepressant before the study starts who get better when they are taken off of it) and placebo resopnders (i.e. those that are not on antidepressants before the study and who respond to placebo). Imagine the converse: an antidepressant washout procedure that eliminates all of the antidepressant responders before a study begins! Such a procedure would surely be considered bias.
2. Penetration of the blind: the double-blind in these studies (where neither the patients nor doctors are supposed to know who is taking the drug and who is taking the placebo) is likely to be unintentionally broken because of the pattern of side effects in the active and inactive drug conditions (Greenberg & Fisher, 1997). When efforts are made to ensure the integrity of the blind, drug effects are diminished. For example, a recent review of the Cochrane database of antidepressant studies using “active placebos” (making side effects more difficult to detect) found very small, non-significant differences between drug and placebo, suggesting that trials using inert placebos overestimate drug effects (Moncrieff, Wessely & Hardy, 2001)
3. Replacement of non-responders: at least six of the studies Kirsch reviewed (of 38) allowed replacement of nonresponders. This means that during the first two weeks of the study, those that were not responding to the drug were removed from the study!
4. Use of sedative medication: Most studies allowed the prescription of a sedative concurrent with the antidepressant. Since other studies have shown that sedatives are as effective in treating depression as antidepressants, how can we possibly know whether the antidepressant effect obtained (if there was one) in these studies was due to the antidepressant drug or the sedative? There are at least 6 points on the 52-point HAM-D scale that the doctors use to determine whether a patient is depressed or not that are related to sleep and favor medications with sedative properties. Since the mean difference between patients taking drugs and patients taking placebos in the studies Kirsch analyzed was only 2 points, it is entirely possible that this small difference is only due to the effects of the sedatives used in the studies and has nothing to do with a true antidepressant drug effect.
5. Reliance on clinician ratings: Given that patients tend to report smaller differences than clinicians (Moncrieff, 2001) one certainly wonders how the pattern of results would change using self-report measures like the Beck Depression Inventory.

Frankly, considering the bias against placebo described above, it is simply amazing that placebo still nearly matched the effects of the drug. Imagine what the results might look like if the trials had been performed without these “anti-placebo” measures!

Also, Kirsch et al. pointed out that the overall active drug effects may have been further inflated because mean results were not reported from several studies that found nonsignificant differences between placebo and active drugs.

The advantage to using the FDA database for analysis is considerable. It contains all of the data from initial trials, published or not, and therefore is not subject to the usual publication bias. (As I mentioned earlier in the article, drug companies simply don’t publish negative results. This is known as the “file drawer” phenomenon, since they probably just stuff those studies in some file drawer hoping they will never be found). Antidepressants are significantly more effective than inert placebos in about two-thirds of published trials. However, in the FDA database which includes unpublished trials, Kirsch found that medication outperformed placebo less than half of the time (in 20 of 46 trials).

Although Kirsch’s study is a meta-analyses, he is also looking directly at the results of individual trials. When less than half of individual trials show any advantage for the active drug over placebo, one must really wonder whether these drugs have any specific “antidepressant” effects.

Now on to the next point.

Actually, it’s not the case that antidepressants work in animal models. According to Joanna Moncrieff in her book The Myth of the Chemical Cure, it is rarely mentioned that all animal models of depression produce variable results according to where they are conducted. “In other words,” she says, “they are unreliable.” In addition to this, they fail to select specifically for antidepressants and responses are obtained with drugs that are not generally considered to be antidepressants (i.e. amphetamines, opiates, antihistamines, antipsychotics, atropine, pentobarbital, zinc and antibiotics).

Also, the SSRIs (the most popular class of antidepressant drugs) typically fail to have any response in the forced swim test, which is one of the most common antidepressant screening tests. In this test, rats are placed in a tank of water from which they cannot escape. The time until they give up trying to escape is measured, on the assumption that the state of giving up is akin to depression. It is thought that antidepressants should prolong the time to giving up. However, the SSRIs have no such effect.

Finally, other tests for depression also frequently show that non-antidepressant drugs (sedatives, stimulants, antihistamines, etc) yield “false positive” results.

I’m not so sure we shouldn’t banish them from planet Earth, to tell you the truth.

Longitudinal follow-up studies (which study the effects of antidepresants over the long term – not just the 6-8 week periods the clinical trials look at) show very poor outcomes for people treated for depression both in the hospital and in the community, and the overall prevalence of depression is rising despite increased use of antidepressants (Moncrieff & Kirsch, 2006). Two studies that assessed outcome in depressed patients treated with and without drugs found that people prescribed antidepressants had a slightly worse outcome than those not prescribed them, even after baseline severity had been taken into account (Brugha TS et al, 1992; Ronalds C et al., 1997). No comparable studies exist that show a better outcome in people prescribed antidepressants.

Outside short-term randomized clinical trials there is virtually no evidence that antidepressants have changed the outcome of depression. The evidence that does exist suggests that they may have possibly made it worse. Depression is more common today than before antidepressants were introduced and the outcome has not improved. Epidemiological trends show that the more antidepressants are prescribed, the more prevalent depression is. Sharply rising levels of antidepressant prescribing since the 1990s have been accompanied by increased prevalence of depressive episodes (Patten 2004) and by rising levels of sickness absence for depression (Moncrieff & Pomerleau 2000).

Finally, there is a growing body of research suggesting that antidepressants worsen the chronicity, if not severity, of depression in many patients. Even relatively short-term exposure to antidepressants has been shown to cause chemical and even anatomical changes in the body and brain that could predispose patients to further depressive episodes (Jackson, “Rethinking Psychiatric Drugs“)

Some might argue that antidepressants are important to stave off suicide in very depressed patients. However, there is no evidence that antidepressants reduce the risk of suicide or suicide attempts in comparison with a placebo in clinical trials (Kahn et al. 2000). In fact, rates have actually increased in some age groups and in some countries despite increased antidepressant prescribing (Moncrieff & Kirsch 2006), and when antidepressant trials have been re-analyzed to compensate for erroneous methodologies, the SSRIs have consistently revealed a risk of suicide (completed or attempted) of between two to four times higher than placebo (ackson, “Rethinking Psychiatric Drugs“)

And we haven’t even talked about side effects yet! Since this article is already very long, I’ll save that for another day. Suffice to say that these are not harmless drugs and the side effects can be severe and potentially fatal.

So I ask you, fair readers, when you add all of this up, should doctors continue to prescribe antidepressants? Let’s see what researchers who have been studying antidepressants and depression for decades have to say:

Moncrieff has actually suggested that the term “antidepressant” is a misnomer, because the drugs have not been demonstrated to have a consistent and specific effect against depression.

If antidepressant drugs were the only option for treating depression, one might still be able to make an argument for their use in spite of their lack of efficacy and risks. However, it has repeatedly been shown that aerobic exercise, light therapy, Cognitive Behavioral Therapy, St. John’s Wort, bibliotherapy (prayer) and perhaps acupuncture (more studies are needed) are just as effective for treating depression as antidepressants – with few, if any, adverse effects. In fact, in the case of exercise many of the side effects produced are beneficial (e.g. better overall health and wellness).

Considering that antidepressants are likely no more effective than placebos, have not improved (and perhaps worsened) long-term outcomes, may increase the risk of suicidal and violent behavior and have significant many other significant side effects and risks, including potentially permanent changes in the brain which predispose patients to further depression… and considering that there are well-established alternatives that are just as effective, if not more so, in treating depression with almost no adverse effects and significantly fewer costs, I see no compelling reason to continue prescribing antidepressants.

Obviously many other people are posing this question, particularly in the medical community. Kirsch’s research has been so widely accepted that the debate has not centered around his conclusions, but on the implications of those conclusions. Ironically, it has been suggested by more than one commentator that although we now know that antidepressants aren’t effective, we should continue to prescribe them – if only in an attempt to elicit a placebo effect.

Huh? Let me explain. One major reason people respond to placebo in antidepressant trials is that they expect the drug to work. They expect it to work because of all of the promotion they’ve seen, newspaper and magazine articles they’ve read, and personal testimonials they’ve heard. What would happen if it became known that antidepressants are, in fact, not effective and that they could actually make depression worse. Bye bye placebo effect.

So some researchers and doctors have actually suggested that we should go on promoting the delusion that antidepressants are effective so that people who are taking them will continue to believe that they are working, which of course significantly increases the chance that they will work.

If these drugs were not so potentially dangerous and harmful, and if there were not proven alternatives, I could almost go along with this deception – although it does raise some very interesting ethical questions. However, the drugs are potentially dangerous and harmful, and there are proven alternatives, so I cannot agree with this approach.

In closing, I just want to remind anyone who is currently taking an antidepressant and thinking about stopping that it is essential you do so under your doctor’s supervision. You will have to gradually taper off of your medication – do not stop abruptly!

As always, I welcome your comments and questions.

In part I we reviewed the environmental and ethical benefits of pasture-raised animal products, along with some general information about why they are more nutritious. In this article, we’ll look more specifically at exactly why grass-fed animal products are superior to commercially-raised alternatives.

Meat

• Meat from grass-fed animals has two to four times more omega-3 fatty acids than meat from grain- fed animals.
• When chickens are housed indoors and deprived of greens, their meat and eggs also become artificially low in omega-3s.
• Eggs from pastured hens can contain as much as 19 times more omega-3s than eggs from factory hens.
• When ruminants are raised on fresh pasture alone, their products contain from three to five times more CLA than products from animals fed conventional diets. CLA is a fatty acid that has recently been studied as a potent cancer fighter.
• The meat from the pastured cattle is four times higher in vitamin E than the meat from the feedlot cattle and, interestingly, almost twice as high as the meat from the feedlot cattle given vitamin E supplements.

Milk

• Unfortunately, 85 to 95 percent of the cows in the United States are now being raised in confinement, not on pasture. The only grass they eat comes in the form of hay, and the ground that they stand on is a blend of dirt and manure.
• Milk from a pastured cow can have five times as much CLA as a grainfed animal.
• Milk from pastured cows also contains an ideal ratio of essential fatty acids or EFAs. Studies suggest that if your diet contains roughly equal amounts of these two fats, you will have a lower risk of cancer, cardiovascular disease, autoimmune disorders, allergies, obesity, diabetes, dementia, and various other mental disorders.
• When a cow is raised on pasture , her milk has an ideal ratio of omega-6 to omega-3 fatty acids. Replace two-thirds of the pasture with a grain-based diet and the milk will have more than five times the amount of omega-6 fatty acids than omega-3s, a ratio that has been linked with an increased risk of a wide variety of conditions, including obesity, diabetes, depression, and cancer.
• Grassfed milk is higher in beta-carotene, vitamin A, and vitamin E. This vitamin bonus comes, in part, from the fact that fresh pasture has more of these nutrients than grain or hay. These extra helpings of vitamins are then transferred to the cow’s milk.

Free-range (pastured) eggs

• When compared to commercially raised, supermarket eggs, free-range eggs have:
  2/3 more vitamin A
• 7 times more beta carotene
• Up to 19 times more omega-3 fatty acids
• Significantly more folic acid and vitamin B12

Raw dairy products – another step up

The information above should convince you that grass-fed dairy products are superior in every way to dairy products that come from grain-fed cows. Another important distinction to be made is the difference between raw and pasteurized dairy products.

I will be covering this in further detail in a future article, but in short raw dairy products have several significant advantages over pasteurized alternatives:

• Raw milk is an outstanding source of nutrients including beneficial bacteria such as lactobacillus acidolphilus, vitamins and enzymes, as well as the finest source of calcium available.
• Pasteurizing milk destroys enzymes, diminishes vitamin, denatures fragile milk proteins, destroys vitamin B12, and vitamin B6, kills beneficial bacteria and promotes pathogens.
• Raw milk is not associated with any the problems of pasteurized milk, and even people who have been allergic to pasteurized milk for many years can typically tolerate and even thrive on raw milk.

Contrary to popular belief, raw milk is safe to consume. There has never been a pathogen found in the milk of the two largest raw dairy producers in California, Organic Pastures and Claravale. In fact, the USDA has been unable to even find pathogens in the soil at Organic Pastures – which is highly unusual. This is due to the much more stringent standards for sanitation that raw dairies must comply with in order to be licensed to sell their products.

Again, I will cover this in more detail in a future article. Stay tuned!

Although most consumers have heard of grass-fed or pasture-raised animal products, confusion still abounds about what their benefits are and why we should choose them over commercially-raised animal products.

It is important to note that the “organic” label does not have anything to do with whether an animal product is pasture-raised or not. It’s possible, and indeed common, for an organic meat or dairy product to come from cows raised in confinement feedlots. Likewise, it is also common to encounter pasture-raised animal products that do not have the “organic” label. This often occurs when the farm raising the animals is too small to afford the expensive organic certification process. In these cases, if one knows the farmer and his or her practices, it is preferable to choose the non-organic, grass-fed source over the organic, commercially-raised alternative.

Many environmental and ethical objections to eating meat stem from the tremendously destructive and cruel practices of commercial feedlot meat production. When meat and dairy animals are raised in a humane and ecologically responsible manner, these objections (which I entirely agree with in the case of commercial production) are no longer defendable.

In this two-part article I will cover the benefits of pasture-raised animal products. In part I, we’ll examine the environmental and economic benefits, and in part II, we’ll look at the nutritional and health benefits. Information is adapted in part from the Eat Wildwebsite.

Back to the pasture
Pasture-raised animals live on the range where they forage on their native diet. They are not sent to feedlots to be fattened on corn, soy or other grains which they do not normally eat. Pasture-raised livestock are not treated hormones or feed them growth-promoting additives. As a result, the animals grow at a natural pace. For these reasons and more, grass-fed animals live low-stress lives and are so healthy there is no reason to treat them with antibiotics or other drugs.

More Nutritious
A major benefit of raising animals on pasture is that their products are healthier for you. For example, compared with feedlot meat, meat from grass-fed beef, bison, lamb and goats has two to four times more omega-3 fatty acids. Meat and dairy products from grass-fed ruminants are the richest known source of another type of good fat called “conjugated linoleic acid” or CLA. When ruminants are raised on fresh pasture alone, their products contain from three to five times more CLA than products from animals fed conventional diets. Grass-fed meat also has more vitamin E, beta-carotene and vitamin C than grain-fed meat.

Factory Farming
Raising animals on pasture is dramatically different from the status quo. Virtually all the meat, eggs, and dairy products that you find in the supermarket come from animals raised in confinement in large facilities called CAFOs or “Confined Animal Feeding Operations.”  These highly mechanized operations provide a year-round supply of food at a reasonable price. Although the food is cheap and convenient, there is growing recognition that factory farming creates a host of problems, including:

• Animal stress and abuse
• Air, land, and water pollution
• The unnecessary use of hormones, antibiotics, and other drugs
• Low-paid, stressful farm work
• The loss of small family farms
• Food with less nutritional value

Unnatural Diets
Animals raised in factory farms are given diets designed to boost their productivity and lower costs. The main ingredients are genetically modified grain and soy that are kept at artificially low prices by government subsidies. To further cut costs, the feed may also contain “by-product feedstuff” such as municipal garbage, stale pastry, chicken feathers, and candy. Until 1997, U.S. cattle were also being fed meat that had been trimmed from other cattle, in effect turning herbivores into carnivores. This unnatural practice is believed to be the underlying cause of BSE or “mad cow disease.”

Environmental Degradation
When animals are raised in feedlots or cages, they deposit large amounts of manure in a small amount of space. The manure must be collected and transported away from the area, an expensive proposition. To cut costs, it is dumped as close to the feedlot as possible. As a result, the surrounding soil is overloaded with nutrients, which can cause ground and water pollution. When animals are raised outdoors on pasture, their manure is spread over a wide area of land, making it a welcome source of organic fertilizer, not a “waste management problem.”