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.


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.

Leave a comment ?


  1. Excellent! I totally agree with you, especially your conclusion.

    Now, if we can just keep BigPharma and Agribusiness from destroying our food supply via government that represents corporate interests over our own…

    Congress is currently preparing to pass a Food Safety bill – be very afraid!

  2. Paul,

    I don’t know what king of bio-identical thyroid hormone you are refering to, but I’m sure you are talking about desiccated thyroid (Armour and others). The “conventional” treatment for hypo, i.e. T4 only drugs, could be harmfull.

    Hypothyroid pacients using conventional treatment (synthetic T4 only) consistently have higher levels of free/total T4 and lower levels of free T3 than euthyroids (Pubmed 20693806, 18285588, 16982586 and 16416346 for some examples).

    Higher total and free T4 levels are associated with increased risk of dementia and Alzheimer’s (Pubmed 17870208, 17136019, 17132968, 16636121).

    Finally, hypothyroids taking thyroid medications progressed more rapidly to a diagnose of Alzheimer’s dementia than hypothyroids not taking thyroid medications (Pubmed 19666883). In this last one they don’t tell, but I assume that thyroid medications were T4 only drugs.

  3. Hi Mario,

    I know that T4 treatment usually doesn’t create a normal T4/T3 ratio, but isn’t the synthetic T4 bio-identical to natural T4?

    Hypothyroid people may often have difficulty with T4 to T3 conversion, which is bad for health. But I’m not aware that that’s attributable to a problem with the synthetic T4.

    I saw that paper about the Alzheimer’s link. Very interesting but I haven’t had time to investigate.

  4. Paul,

    I don’t enter the merit if synthetic T4 is bio-identical or not! That’s not the point.

    I think what matters is that a treatment with only a part of what a normal thyroid produces (T4, T3, T2, T1 and calcitonin) could translate in abnormal levels of T4. What would be the consequences of this? Well, a increased risk and rapid progression to Alzheimer’s could be one…

    • Yes, Mario, quite right. We always prefer natural healing with iodine and selenium and vitamin D supplements and removal of goitrogens and other food toxins that damage the thyroid and promote autoimmunity.

      When I said those drugs were the most likely to be helpful, I didn’t mean that they couldn’t be harmful. An overdose of insulin or of T4 will do harm. But they can help relieve a problem. They can also be diagnostic: the response to T4 can help distinguish a deficit in T4 to T3 conversion from, say, an iodine deficiency.

      Bio-identical compounds and antibiotics always have to be taken with care. I just think they have a much higher probability of avoiding the kind of disastrous side effects seen with gene-targeting drugs, and a much higher probability of delivering benefits.

      Thanks for telling us about the T4 risks. That’s a nice set of papers.

  5. Mario wrote, “I don’t know what king of bio-identical thyroid hormone you are refering to, but I’m sure you are talking about desiccated thyroid (Armour and others).” Actually, desiccated thyroid preparations such as Armour are anything but bio-identical for humans. For pigs, they are, since pig thyroids are the source.

    The T4 and T3 molecules may be the same (I don’t know), but pig thyroid extract has a very high T3 to T4 ratio (about 20%). Some people say they feel good on these meds, but after experimenting with varying T3/T4 ratios with thousands of hypothyroid patients over many years, my doc (Kenneth Blanchard, Ph.D., M.D.) has concluded that the great majority of humans do best on less than 1/10 of that ratio, about 1.5% T3 relative to T4 taken orally. There is a significant variability, but only a handful seem to fare best on either 100% T4 or 100% pig thyroid extract.

    That kind of “functional” testing is, to me, the only rational way to determine optimal approaches to health problems. Even if it were true that pig and human thyroids contain similar ratios of T3 to T4, what happens when we eat the pig thyroid extract? T3 is far better absorbed in the gut than T4, so that concentrates the T3 dose. What happens in the liver, which can interconvert thyroid hormones? How do we account for genetic differences between people, not to mention different diets and gut functioning? The only way to determine the best approach is functional experimentation. Just taking what is marketed as a “natural” product is not a reliable guide at all.

    By the way, I agree with Paul that bio-identical hormone replacement is one of the few shining examples of terrific drug therapies. I’d be dead, or close to it, without my thyroid meds by now–although thanks to iodine supplementation, probably in concert with dietary changes, I need far less of it than I did before. One way to see this is to look at the “number needed to treat” measure of a drug’s effectiveness. With good drugs such as thyroid hormone or insulin, that number is close to one. Just about every single person appropriately treated gets better.

    Compare that to many commonly used drugs, where the NNT is so high it takes massive studies to even distinguish it from infinity. Statin drugs are one example. In these cases, even if there is a benefit (questionable for statins), what about the vast number of people who aren’t helped but are nevertheless exposed to the inevitable negative effects? This is the reality of many drugs and other medical interventions: they are extremely weak sauce, so their benefits are easily drowned out by their dangers.

    I know it’s annoying, but when my doctors or veterinarians suggest using a drug, I ask what the number needed to treat is and what the rates of long term negative effects are. How can one decide rationally whether to use the drug without that information? They never know.

  6. Hi Paul,

    Quick question about HbA1c, if you happen to know about this or have any thoughts…

    Just this morning, I took my A1c home test (by Bayer) which includes two tests in the box. Because of the unbelievably low result of first test, I took the second one (different finger, different hand) to check… Results:
    test 1- 5.2
    test 2- 5.3
    (remember I’m type 1 diabetic)
    So, as I do often, I averaged out my 50 stored numbers on my blood glucose meter just to compare (even though I know they won’t necessarily match up since the tests measure different things)– my average of the last 50 BG readings was 120.68 (which should be closer to 5.8 A1c)
    So, my husband got me another home test and I just took a third one (I was hoping this was a miracle moment for me!!) Third test result: 5.8. Darn. Not what I was hoping! But, we decided that I will take the fourth test tomorrow morning, fasting again to be sure. (the third test was about an hour after I had eaten breakfast). I called the Bayer helpline and they said I don’t need to be fasting for the test, but I’m wondering if that’s inaccurate. (at least I’m hoping so!)

    So, do you think that even though my daily BG readings average out to 120 (measuring free glucose in blood) that there could be some very helpful and positive process going on in my body which is preventing the hemaglobin of red blood cells from becoming glycosated? Can lots of extra vitamin C accomplish this? Or Vitamin D? Aside from a regular multivitamin, C and D are the two regulars I take almost daily.

    Any thoughts?

    I’ll still report back tomorrow morning with results of fasting test #4. I hope to have good news, no matter if someone tells me it’s impossible!

    **side note: I am getting lab work done at dr. on Tuesday anyway, so that will shed some light on things. But my dr. is hard to get on my side and I need to do some things on my own because we are definitely not on the same page.


  7. Just a quick report on my A1c this morning…

    (sorry, I think I should’ve posted this somewhere else… I had originally clicked on the “Diabetes” category but didnt realize til after I posted that I was writing under “Drugs: often unsafe at any dose” page)

    Anyway, my result was 5.6 this morning. I guess this is inconclusive! I’ll just wait for my official labwork to come back and see where it’s at. In any case though, I’m very delighted with 5.8 if that’s where it ends up. I know the diet here is helping me a lot and I’ve been feeling more energetic lately and less moody, which my husband is VERY HAPPY about!! 🙂


  8. Hi KH,

    HbA1c is affected by a number of things besides average blood glucose level, notably how long red blood cells stay in the blood. So the numbers can easily vary by 0.6 in either direction from what tables would predict.

    I think improved micronutrient status helps, as will keeping iron levels low.

    These are great numbers for a diabetic! Congratulations! I’m very happy you are feeling well too!

    Best, Paul

    • Hi Paul,

      This is an old post, but I’m wondering if there is a way to test for brain infection? Would any sort of blood test reveal such? I am in generally very good health, but have problems with stress that manifest as mild depression and occasional anxiety. However, I recently had a metametrix and it didn’t show any pathogens… Would an infectious agent also be present in the gut?

      It’s rather difficult to guess if I have a brain infection or not.. And without a doctor that is just willing to throw antibiotics at my theory it might be impossible to find treatment. I have been eating your diet for well over a year and feel generally good, but still have problems as mentioned above. My doctor has recommended low dose Prozac.. But now of course this post gives me pause. Any suggestions?

      I should note, I am fine with regular fasting, but a brief stint of keyogenic style fasting made me feel way too wired and weird. That could be due to the heavy load of emotional stress I was facing at the time.. And therefore just not ideal for me hormonally.
      It’s hard to say.

      In short, I wouldn’t say I’m depressed really, but rather chronically
      Stressed which manifests as periodical depression, body aches and obsessive thoughts. Do you think these symptoms are enough to indicate a brain infection?

      Thank you,


      • Hi Lindsay,

        It’s difficult. In fact diagnostic testing for nearly all chronic infections is in a very primitive state, and the brain is the worst because it’s the least accessible organ and basically has its own immune system behind the blood-brain barrier.

        So, seeing if antibiotics have an effect is probably the most straightforward way to test for infections. Of course that only works if the microbe is susceptible to the antibiotic, and it may take some time to get a good reading.

        No, infectious agents don’t need to be present in the gut, though they often enter the body from there when initiating the infection.

        I think an infection would be consistent with those symptoms, but we don’t know enough to say what other causes could create similar symptoms, or to pin down what type of infection it would be.

        I wish doctors in these circumstances were willing to do a series of controlled experiments with (say) doxycycline as an antibacterial drug, fluconazole as an antifungal, and some low-risk antiprotozoal drug, each one at a time with a no-drug break inbetween, just to see if one of them has an effect. But I haven’t yet met a doctor who would do that.

        Best, Paul

  9. Considering the side effects of Prozac are pretty terrible sounding I am willing to try just about anything else. I have access to a fair amount of antibiotics, one of which is 100mg doxy. I guess I will just start taking that and see if I notice a change. I tried them once before for 2 days, but didn’t notice much.. maybe I was looking too hard? How long would you expect to notice a change if the doxy is in fact working?

    Also, are there common protozoa that inhabit the brain?

    • Hi Lindsay,

      I noticed an effect from doxy from the first pill — I went immediately from irritated, low, unhappy to euphoric. That was when I needed it. When I didn’t need it, I noticed nothing.

      Toxoplasma is a common protozoal infection of the brain.

  10. Paul, I very recently (until yesterday) took metronidazole for an amoeba and blastocystis infection (diagnosed by stool test). While on a very restricted diet (which is my normal diet, because of food sensitivities, but not indigestion), gastrointestinal effects are very reduced, except from maybe some constipation and maybe an increased tendency to hypoglycemia, though not very clear, because I have suffered from those from a long time ago. However, otherwise digestion is bad, especially of sugars (which I not normally eat). This last symptom got much worst since a recent infection, probably with one or both of those microbes, which came as an attack of gas, diarrhea and some nausea. Also there have been instances, before and after, of strong colicky pain, and butt itchiness, but they are uncommon and not predictable.

    The first day (or days) of taking the antibiotics I felt ok, but then I had very reduced energy and some weird mental state and reduced mental acuity. Then I felt better (for like a day), but still with less energy than normal. The next day, the last one of the five day course, I felt bad again, close to before, though taking some vitamin C helped.

    I guess that was all die-off, but I have a couple of questions. First, how can one differentiate die-off effects of an antibiotic drug from inherent toxic effects of such drug. Second, if at the time of stopping the drug, you still have die-off symptoms, then is it really ok to stop it? Can’t it mean the infection(s) is still there? Sorry for the long post, and thank you infinitely for your time.

    • Hi Juan,

      It’s not necessarily easy to distinguish. Elimination aids like bentonite clay or activated charcoal will help with toxin removal, so if they provide benefit then it’s more likely to be detox. There are tests for things like pyroluria. But metronidazole can definitely generate negative effects, so it’s a good idea to consult your doctor.

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