Drugs: Often Unsafe at any Dose

If you have impaired health, go see a doctor.  Use them first for diagnosis; doctors can do lots of tests to help clarify your condition, and they have tremendous clinical experience and great insight into many conditions. But be wary of their drugs. Do your own independent and critical evaluation of any drug recommendation.

The most helpful drugs are of two kinds:

  • Bio-identical replacements for deficient human compounds. Think insulin for diabetes, or thyroid hormone for hypothyroidism.
  • Antibiotics for conditions in which the causal pathogen is known or strongly suspected. The trouble here is that in many chronic diseases, the pathogens which cause the disease are not known. Choosing the wrong antibiotics may do more harm than good.

Most other drugs are designed to ameliorate some disease symptom, at the cost of introducing new health problems elsewhere. Over time, these negative effects often prove far more damaging than the drug’s benefits.

I explained why a few posts ago:

Much pharmacological research in recent decades has been devoted to “targeting” individual proteins or genes, and seeing if these interventions produce beneficial results in some disease or other….

The human body is the result of a long evolutionary history. Our ancestral genome reached its current size, about 20,000 genes, prior to the Cambrian explosion. For over 500 million years, the thrust of evolution has been to make the gene-protein network as sophisticated as possible, as densely networked with subtle interactions between as many molecules as possible. Every gene has an important role to play in that network, and directly influences perhaps a hundred partners. Thus, targeting a single gene will not only deprive the body of that gene’s function; it will also deprive that gene’s hundred partners of the benefits of its interactions, and thus impair their function, which will have ramifications upon their partners, until the whole genome has been affected. Thus, all interventions in the human body have systemic effects. It is not possible to confine effects to a single “target.”…

If the human body is a highly-optimized densely-networked system, then we must be skeptical toward the “black-box” school of medicine – especially in its new, reductionist, human-gene-targeting form. If evolution has optimized the human gene network to maximize human health, then targeting human genes and proteins is sure to sabotage health, probably in unexpected and insidious ways.

Then, responding to my very next post, Joe D gave us some neat information indicating that the drugs used to treat depression may increase mortality by 30%.

Now Jenny Ruhl, the excellent author of Blood Sugar 101 and proprietor of Diabetes Update, points out that some diabetes drugs are backfiring spectacularly, inducing crippling bone failures and cancer:

A long term study of  Actos [PAJ: pioglitazone] discovered that there is a clear dose and time-related increase in bladder cancer among those who take it.…

Today’s newer generation of drugs target specific genes and cell receptors. The TZD drugs, Actos and Avandia, target the PPAR-gamma transcription factor which regulates genes that affect how lipids are stored….

PPAR-gamma, for example, transforms the bone stem cells that should turn into new bone into new fat cells. This is why after a decade on the drug many people start experiencing broken bones in their arms and legs (the areas where PPAR-gamma is most active) and why once bones begin to break there is no cure. A decade of rebuilding has been subverted and the weakened structure of the bone cannot be fixed.

Jenny observes that the drug approval process, which evaluates for safety over short time periods and efficacy against a specific disease, doesn’t evaluate long-term safety issues:

And this points to the huge problem with the drug regulation process. There is no requirement–none, zilch–that a company applying for permission to market a new drug investigate what OTHER physiological processes are affected by the drugs’s mechanism. All the drug company has to show is that it achieves what they are selling it to do. In the case of Actos and Avandia, that means causing a very modest drop in A1c–about .5%….

Many of these life-ruining side effects happen so slowly they don’t show up for five to ten years–and then it takes a lot of work to link the side effect to the drug….

That is why evidence a that a drug is raising the incidence of cancer rarely appears until a drug is almost at the end of its 14 year patent period. It has taken more than 12 years to notice the link between bladder cancer and Actos. It took nine years after its approval for anyone to notice the signal suggesting that Diovan raises cancer incidence by about 8%.

And that’s why it won’t be until another nine years or more that the public will learn that any drug that inhibits DPP-4 is turning off an immune system mechanism essential to fighting melanoma, prostate cancer, ovarian cancer and lung cancer. Details HERE.

Visit Jenny’s blog to see why Metformin is the only diabetes drug known to be safe, and her recommended changes to the drug approval process. In my view, Jenny’s proposed changes would radically downsize the pharmaceutical industry. Few drugs would pass her filter.

Conclusion

The most powerful and effective way to improve health is through diet and nutrition. Put off drugs until you’ve fixed your diet, and there’s a good chance you won’t need drugs at all.

Depression Is Deadlier Than Coronary Heart Disease

I thought this was a remarkable statistic:

Those with coronary heart disease alone were 67% more likely to die of all causes, while those who were depressed, but otherwise healthy, were twice as likely to do so as those who had neither condition.

But those who were both depressed and had heart disease were almost five times as likely to die as their mentally and physically healthy peers. [1]

If you are severely depressed, or have any other mental health condition, do not just live with it. Your condition may reflect some defect with diet or nutrition that may lead to long-term harm if not remedied. Or it may be caused by an infection which, if not treated, will progress.

One trouble with infections is that all infectious pathogens have evolved ways to disable the immune system, so any one infection makes you more vulnerable to subsequent infections. This is why people with chronic diseases and the elderly generally have many chronic infections at the same time. Each infection is debilitating; but as the number and severity of infections grows, the body weakens. Eventually, pathogens will induce some acute condition like pneumonia that enables them to spread to new hosts, and their first host will die.

I suspect that depressions of infectious etiology are more deadly than coronary heart disease because they imply a more advanced infection. Generally, to infect the brain pathogens have to first infect the vasculature; the vascular infection enables them to cross the blood-brain barrier. One can have a vascular infection (and coronary heart disease) without a brain infection, but as a rule one will not have a brain infection without vascular infection.

The drugs that doctors use for mental health conditions generally moderate symptoms but do not cure. By all means, see the doctors, but don’t expect a cure from psychoactive drugs. So what should you do?

I believe that the best treatment for depression, as our last post suggests, is a ketogenic variant of a healthy diet, good nutrition, and (if an infection is present) appropriate antibiotics. It is wise to start with diet and nutrition first, since diet alone may cure many conditions and a good diet is entirely safe. A healthy diet can greatly enhance mood. Antibiotics have the potential to backfire, so are the last line of defense; but in severe infections will be necessary for a cure.

References

[1] Depression and heart disease combo more lethal than either one alone, study suggests. ScienceDaily. September 16, 2010. http://www.sciencedaily.com/releases/2010/09/100915205716.htm. Nabi H et al. Effects of depressive symptoms and coronary heart disease and their interactive associations on mortality in middle-aged adults: the Whitehall II cohort study. Heart. 2010 Sep 15. [Epub ahead of print] http://pmid.us/20844294.

Curing Arthritis and Depression with Diet and Antibiotics

Most chronic diseases are considered incurable. But if cures are rare, it may only be because doctors and patients rarely try the proper dietary and antibiotic therapies.

Two smart commenters who figured out how to make progress against their own chronic diseases refute the notion that disease progression is inevitable.

Arthritis

First, Michelle cured her arthritis with diet and antibiotics:

I’ve successfully put RA into remission using low dose, pulsing antibiotics, based on the work of the late rheumatologist Dr. Thomas McPherson Brown. I’ve been a low dose of Doxycycline, 100 mg, on MWF, for a little over two years now. My joints are no longer reminding me of my arthritis daily.

For background reading, check out “The New Arthritis Breakthrough” by the late Henry Scammell. “Why Arthritis?” by researcher Harold Clark is good too.

A few months before my arthritis reared its ugly head, I gave up gluten. In the last year, I’ve weaned myself off the myriad GF products such as GF cookies, bread & pasta. We’re buying meat from healthy animals a local farm. I’ve gotten reacquainted with butter, cream, and I avoid PUFAs like the plague.

I’m keeping an eye on my fluctuating thyroid function, and fluctuating progesterone levels (I’m 47). Taking probiotics. Checking Vit. d levels.

I’m sure all the positive changes have contributed to the remission, but I feel certain the low dose pulsing antibiotics got me over the hump.

I noted that many if not all cases of arthritis are caused by infections, with C. pneumoniae probably the most common agent, and Michelle replied:

Yes, I had a panel of tests done at The Arthritis Research Center (www.tarci.net).

The lab checked for strep, plus mycoplasma (M. hominis, M. fermentans, M. salivarium, & M. pneumonia), plus chlamydia (C. pneumoniae, & C. trachomatis).

Ding! Stealth infections!

Michelle’s infections included M. hominis, C. pneumoniae, and C. trachomatis. It’s quite common to have multiple infections, even in the general (“healthy”) population as we noted in this post. So it’s no surprise there was more than one.

Michelle’s doctor recommended low-dose doxycycline (100 mg three days a week), which took 2+ years to cure the arthritis. She might have been cured quicker with a larger dose. As she describes the issue:

I understand there’s controversy about stealth infections. Some say they are very difficult to treat, and one needs to throw the kitchen sink at them— high doses, daily dosing, rotating various antibiotics. My MD felt that many people were having trouble with stealth infections because they were over-treating. High, daily dosing makes the situation worse for many.

When I questioned this, he reasoned that we can always raise the dose later, or switch up antibiotics later. As it turned out, I made progress on a small dose. It was slow going, but 2+ years later, I no longer worry about being crippled by arthritis.

Dosage is a tricky issue.

  • Higher levels of antibiotics are more likely to denude the gut of probiotic bacteria, and populate it with pathogenic species that shelter from the antibiotics in biofilms, or with fungi that are immune to the antibiotics. The loss of probiotic species in the gut can lead to new infections; immune cells go to the gut to fight pathogens there, get infected themselves, and then go to joints to fight infections there, and spread their pathogens into the joints. Thus, there is a potential to add new pathogens to the joint infection, compounding the arthritis.
  • On the other hand, lower levels may be insufficient to clear the infection, or may take inordinately long to do so. If the duration of antibiotics is longer, gut problems may be as severe on low antibiotics as on high.

My own prejudice is “go as fast as you can but no faster,” but clinical experience will teach us the best course in different diseases. In more severe diseases – multiple sclerosis, for instance – low-dose monotherapies have no chance and high-dose combination protocols are needed.

The potential for antibiotics to backfire is why you want to adopt all the dietary and nutritional steps first (in our book Steps 1, 2, and 3), then pursue antibiotics and therapeutic diets (Step 4 in the final version).

Depression

Second, Winalot has made progress against depression and suicidal tendencies by eating a ketogenic diet:

I’m zero-carb as I’ve found Ketosis has greatly reduced my depression / suicidal tendencies, however I do worry that this might not be “healthy”.

You mentioned “some mental health and neurological disorders, may benefit from very low-carb “ketogenic” diets” and I was wondering if there’s any more advice you can give on finding that sweet spot?

Ketosis hasn’t cured me, I still have bad days and take SSRI’s but it’s certainly better than boatloading carbs for “serotonin” like I used to.

It’s very smart of Winalot to have found the ketogenic diet. A ketogenic diet has two major benefits for infectious brain diseases:

  1. Ketones induce neuronal autophagy, which means they upregulate the primary intracellular immune defense mechanism against bacterial infections.
  2. Ketones are neuroprotective. One mechanism: They are an alternative energy substrate for neurons. Bacteria steal pyruvate and other glycolytic products for their own energy metabolism, depriving neurons of their main energy source and inducing the cognitive symptoms of hypoglycemia in the brain. But bacteria cannot consume ketones. If ketones are supplied, neurons do not starve. Starvation is probably the main cause of neuronal death in many of these diseases. If you don’t wan’t to suffer the shrinking brain that is so common in Alzheimer’s, multiple sclerosis, and other infectious brain diseases, a ketogenic diet is prudent.

Winalot asked for a “sweet spot” and I gave the following advice:

In general, I recommend 200 starch calories a day. This will not prevent generation of ketones if you take a lot of ketogenic short-chain fats and will protect you against glycoprotein deficiencies leading to bowel cancers and other nasty long-term side effects, not to mention impaired immunity against extracellular pathogens.

This should be accompanied by a boatload of coconut oil for those ketogenic fats. I suggest about 1500 calories / 6 fluid ounces / 12 tbsp coconut oil per day. This sounds like a lot, I know, but it is therapeutic.

Also, get 400 protein calories per day. This is higher than our normal protein recommendation.

Finally, I highly recommend antibiotics, since I believe bacterial infections of the brain (leading to tryptophan sequestration by interferon-gamma and IDO) are far and away the most likely cause of your depression and serotonin deficiency. I would start by assuming this is C. pneumoniae, the most common brain pathogen, and take the Wheldon protocol antibiotics. You can find a good guide at http://cpnhelp.org.

Tryptophan sequestration is a primary intracellular defense against bacterial infections, and bacterial theft of tryptophan from serotonin also tends to denude infected cells of serotonin. We regard serotonin deficiency symptoms as prima facie evidence for a bacterial infection of the brain. C. pneumoniae is the most common bacterial pathogen in the brain, so antibiotic strategies that are proven against C. pneumoniae are a good place to start against depression.

Doxycycline is a good first antibiotic; it enters the brain well and is active against C. pneumoniae. The response to doxycycline also has diagnostic value. If you don’t have an infection, usually there is no obvious effect to the antibiotic. If you do, there are usually clear effects, either good or bad:

  • Good, because doxycycline is a protein synthesis inhibitor and will slow down bacterial activities that may be damaging you, including tryptophan theft. You may experience euphoria for a few days, followed by richer emotions and relieved depression.
  • Bad, because it may produce either toxicity effects from bacterial die-off (endotoxins and porphyrins) or other side effects. For instance, C. pneumoniae inhibits apoptosis (cell death) of immune cells, and inhibition of protein synthesis will stop this and may be followed by the immediate suicide of most white blood cells. This sudden drop in white blood cell count could lead to a surge in fungal or other infections, lasting several weeks until new white blood cells can be manufactured.

If you notice such effects, continue the doxycycline, but modulate doses so that the bad effects are not too severe. Other antibiotics can be added in combination once the bad effects are modest.

Conclusion

The thesis of this blog is that most chronic diseases can be cured in a two-part process:

  1. Good diet and nutrition should be used to eliminate toxicity syndromes and empower the immune system.
  2. Antibiotics can then be brought to bear against entrenched infections to work a cure.

Diet and nutrition should be the first step. A good diet will clarify symptoms and help diagnose pathogens; minimize antibiotic doses and duration needed for a cure; and minimize die-off effects from bacterial endotoxins and porphyrins during antibiotic treatment.

It’s great to hear from people who are making progress against their diseases. Hopefully, our book and blog can generate many more such cases. Abundant cures will do more than billions in research funding to teach doctors and scientists how to treat these diseases.

The Philosophy of this Blog, With A Parable

One (dis)advantage of the Internet is that it offers a forum for rants: passionate expressions of opinion.

Of course, one man’s passionate opinion can, from another perspective, appear to be nutty-as-a-fruitcake insanity.

My Nutty Post on the Corruption of Medicine

An incisive comment from Christopher M points out that my recent rant on the corruption of medicine is silly:

I think you go too far in your criticism of creeping disease-ification. You seem to have embraced the idea that we should ignore damage and decay to the human body if it is somehow “natural” — i.e., major muscle loss in the aging and elderly. But this is silly. Human suffering, decreased quality of life, and death are problems whenever they occur. Now, maybe the “disease” model isn’t always the best way to think about these questions. But I can’t imagine why we would want to carve out certain forms of decay and suffering as parts of the human experience to tolerate rather than try to avoid — with whatever imperfect means we can.

Now this is obviously correct. Human suffering and decay should be remedied wherever possible.

Christopher could have added to his critique. Doctors, scientists, drug companies, politicians and bureaucrats – all are well-intentioned, eager to heal the sick. How can it be fair to say that their industry is, in some ways, corrupt? Their intentions are good and they work tirelessly in the hope of turning their good intentions into good deeds.

And if they make a lot of money, what of it?  The laborer deserves his wage.

The Black-Box Perspective of Medicine

Conventional medicine is largely based around drug treatment, and drug treatment is based on a reductionist model of human health.

In this model, the human body is a sort of “black box” of which we know little. Drugs are interventions that affect the black box. Health is an output of the black box, characterizable by observable markers (such as, is the black box warm and moving, or cold, stiff, and still?). Medical research is conducted empirically. We do an intervention – provide a drug to the black box – and the black box tells us if it feels better or worse (or we look to see if its box-heart still beats). Millions of drugs are sorted through to find a few thousand that make the black box perform its box-functions a bit better, at least in the short term.

Obviously, this black-box model made a lot of sense before we knew about the human genome, before we could do molecular and cellular biology. It is how our Paleolithic ancestors discovered medicinal herbs. Many early drugs were refined from traditional herbal medicines.

In the modern genomic era, this black-box model of medicine has persisted with a reductionist approach to molecular medicine. Now that we’ve sequenced the human genome and can design drugs to target individual proteins, biologists can at will eradicate the function of any human gene or protein we choose. Much pharmacological research in recent decades has been devoted to “targeting” individual proteins or genes, and seeing if these interventions produce beneficial results in some disease or other.

So, from this perspective, it makes sense to say:  Let’s make a drug that targets a human enzyme – say, HMG-CoA reductase – and see if it can provide any benefits in some disease. Since HMG-CoA reductase is needed to make cholesterol, and cholesterol is correlated with high rates of heart disease (and low rates of infectious disease and cancer), perhaps targeting HMG-CoA reductase will have benefits in heart disease patients. So let’s do a trial, see if HMG-CoA reductase inhibitors make heart attacks less frequent. If so, let’s stuff heart disease patients with these inhibitors at a cost of $25 billion a year.

And this makes great sense – if all you know about human beings is that they resemble black boxes.

An Alternative Perspective

Now step back from that conventional perspective on health, and consider an alternative point of view that extrapolates from a few facts:

  • The human body is the result of a long evolutionary history. Our ancestral genome reached its current size, about 20,000 genes, prior to the Cambrian explosion. For over 500 million years, the thrust of evolution has been to make the gene-protein network as sophisticated as possible, as densely networked with subtle interactions between as many molecules as possible. Every gene has an important role to play in that network, and directly influences perhaps a hundred partners. Thus, targeting a single gene will not only deprive the body of that gene’s function; it will also deprive that gene’s hundred partners of the benefits of its interactions, and thus impair their function, which will have ramifications upon their partners, until the whole genome has been affected. Thus, all interventions in the human body have systemic effects. It is not possible to confine effects to a single “target.”
  • Hundreds of millions of years of selective evolution have optimized the human body to work very well if it obtains appropriate inputs: a good diet that is nutritious and free of toxins.
  • However: the human body is not alone. It is saturated with microbes – trillions of them –which have evolved independently to be effective parasites upon humans. These microbes sabotage the immune system, steal nutrients, obstruct the functioning of human proteins. Their goal is their own reproduction, and human health is only incidental to that goal. Some of them benefit from a healthy host, and these microbes are called “probiotic.” Some benefit from harming their host, and these are called “pathogens.”

From this perspective, what is likely to cause disease? Three factors are most obvious:

  • A malnourishing diet may deprive the body of needed nutrients.
  • Toxins, especially food toxins, may poison the body.
  • Pathogens may sabotage the body in pursuit of their own advantage.

If disease results from these causes, then we are forced to look to diet and nutrition as the first step toward health. And then to infections, which may be treatable with antibiotics, as the second.

If the human body is a highly-optimized densely-networked system, then we must be skeptical toward the “black-box” school of medicine – especially in its new, reductionist, human-gene-targeting form. If evolution has optimized the human gene network to maximize human health, then targeting human genes and proteins is sure to sabotage health, probably in unexpected and insidious ways.

A Parable

I often use economic analogies, because there are a lot of parallels between the cooperative functioning of people in a complex modern economy and the cooperative functioning of cells and molecules in the human body. Let me offer an economic parable.

Imagine a world in which every person manages a complex factory. This factory has tens of thousands of workers, and complicated machinery of thousands of varieties, which all has to work together cooperatively if the output of the factory is to be high.

Suppose that from time to time a factory suffers a loss in output. The workers don’t seem to be as effective; they occasionally fall down and die in the middle of the workday. Machinery breaks down for no apparent reason.

Suppose that, in fact, this is due to an invasion of the factory by malicious monkeys, who steal machinery parts, and ravenous wolves, who kill the workers. Suppose that food poisoning in the factory cafeteria has left the factory security guards and workers weakened and unable to defend themselves and their machines. Suppose further that the malicious monkeys and ravenous wolves are invisible.

One day your factory experiences such a slowdown, and you hire a “factory doctor” to help you fix the problem.  He explains that the reason for the decline in factory output is that your workers and security guards have gone bad. The factory has an “autoimmune” syndrome in which rogue security guards kill workers. Workers have been damaging machine parts. The solution?  Hire a sniper team and kill some workers. Remove the damaged machine parts and don’t replace them. Lock the security guards in the break room. The cost? A mere $20,000 a year, charged to your insurance company.

Now suppose another consultant comes to you.  His explanation: your factory has been invaded by monkeys and wolves. Food poisoning has prevented the security guards from driving them out. His solution?  Give better food to the security guards. Put a fence around the factory to prevent more monkeys and wolves coming in. Find an “infectious monkey and wolf doctor” who can “diagnose” the infection, making the monkeys and wolves visible. Then use his “antibiotic” team of monkey and wolf assassins to kill the invading animals. DO NOT KILL ANY OF YOUR WORKERS OR LOCK UP YOUR SECURITY GUARDS. The cost of this analysis? $25 – free if you can assemble the diagnosis from information scattered across hundreds of blog posts.

The Problem of Underemployed Sniper Teams

Now suppose that factory owners are not hiring enough sniper teams at $20,000 per year. So the factory doctors start going to factories with high output and saying to the owners, “Your factory has pre-disease. Although nearly all your workers and security guards are functioning well, a few have gone rogue. If you hire our sniper team and let us assassinate some security guards and workers, your factory will perform even better. Won’t you hire a few snipers?”

The $25 consultant responds with a nutty rant.

Conclusion

This parable is a work of fantasy. It bears no resemblance to any medical industry or blogger you may have encountered. Any resemblance to any actual medical industry or blogger is purely coincidental.