The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 19 No. 2 • February 2016


An Emerging World of Medicine—Low-Dose Medications—Points to a Revolution in the Treatment of a Diversity of Diseases

Recently, versions of common drugs that are used to treat diseases within a certain dose range (as defined in the FDA approved descriptive material that accompanies the drugs) have begun to appear in published experiments and in actual clinical use at far lower doses. These much lower doses have proven to often have rather different effects and to be useful for other conditions. Of course, at the reduced dosage the risk of adverse effects are reduced as well. The use of FDA approved drugs is not approved for their low dose forms, but as is well known, physicians are free to prescribe such usage to patients. These low dose forms are frequently manufactured by compounding pharmacies.

We note a few examples here. (In doing so, we are NOT either recommending or not recommending their use, but only giving them as examples of how the low dose medication field is advancing.)

LOW DOSE PROPRANOLOL

Low dose propranolol (where propranolol is a beta blocker, an antihypertensive medication used typically at 2 to 6 mg/kg per day, was administered to rats in a model of periodontal disease. They received propranolol at 0.1 mg/kg, 5 mg/kg, or 20 mg/kg per day. Divide these figures by 6.2 for the human equivalent dose. “Propranolol at 0.1 and 5 mg/kg reduced the bone resorption [loss of jawbone] as well as ICAM-1 and RANKL expression [markers of inflammation]. However, only the 0.1 mg/kg reduced IL-1beta, TNF-alpha and CTX levels as well as increased the expression of OPG...” RANKL induces oxteoclastogenesis (osteoclasts reduce bone mass). IL-1beta and TNF-alpha are powerful inflammatory cytokines. The human-equivalent dose used here is 1% or a bit less than the usual dose for hypertension, with no blood pressure lowering side effects at this dose!

A particularly interesting study showed that low-dose propranolol was effective in preventing postoperative supraventricular tachyarrhythmias (Silverman, 1982), a common cause of death in patients who have had heart attacks and then undergone surgery for graft replacement (coronary artery bypass). At the low dosage administered (10 mg orally every six hours starting the morning after surgery) patients exhibited no significant morbidity, “yet significantly decreased the incidence of postoperative SVT [supraventricular tachyarrhythmia].” (Silverman, 1982).

The authors of the low dose propranolol study for postoperative arrhythmias (Silverman, 1982) explained that propranolol has “proven efficacy” for the prevention and treatment of a variety of tachyarrhythmias, but that abrupt withdrawal could initiate “acute ischemic events.” Hence, they wanted to determine whether low dose propranolol might be effective and yet have a reduced risk of these adverse events.

Preoperatively, patients with stable angina had their propranolol treatment tapered to 40 mg every 6 hours by the day before surgery (if receiving a lower dose, they were continued on that dose) and then to 10 mg every six hours following surgery. Certain other medications were discontinued (details in paper). Three of 50 patients (6%), who were called Group I, developed supraventricular arrhythmias as compared to 50 patients (the controls) in which 14 (28% developed such arrhythmias. This result was significant.

The results of human and animal studies suggests that the low dose of propranolol has beneficial effects with fewer side effects as compared to the high dose of propranolol usually given to treat hypertensive patients.

LOW DOSE NALTREXONE

Naltrexone, an antagonist to opioid receptors, is often used to treat patients who have ingested an overdose of opiates. In the form of low dose naltrexone, however, it has been found to be useful in treating a variety of diseases, including several types of cancers (an example is pancreatic cancer, (Berkson, 2006)), COPD, itching pruritis, (Frech, 2011), ALS, Alzheimer’s disease, Systemic Lupus, Irritable Bowel Syndrome, and the list goes on (see Low Dose Naltrexone homepage, www.lowdosenaltrexone.org/ )—NOTE: we have not evaluated more than a sampling of the contents of this website. You should contact your physician, knowledgeable about the use of low dose naltrexone, before trying anything suggested here.)

LOW DOSE LITHIUM

LOW DOSE INSULIN

LOW DOSE CLONIDINE

Other substances or drugs that offer a different result when used at low doses as compared to higher doses include lithium enhancement of memory (Tsaltas, 2007); reduction of suicides (Ohgami, 2009); low dose insulin improves age-related cognitive deficits (Maimaiti, 2016); low dose clonidine (a blood pressure medication) shown to have beneficial effects on adolescents with chronic fatigue (Fagermoen, 2015) and many, many others. This field of medicine is expanding rapidly.

How Do The Low Dose Medications Work?

One hypothesis is that in some cases, low dose medicines may act as hormetic agents, where very small amounts of a substance induce counteracting mechanisms that provide protective effects.

Another possibility is based on the fact that a medication frequently works as an inverted “U” shaped curve, where at low doses, the pharmacological effects are different at the left side of the inverted U, and then at the peak of the curve and over to the right side toward higher doses, the effects again change. Of course, the higher doses are associated with a greater risk of undesirable off-target effects.

We suspect, in addition, that in some cases there may be a subset of receptors to which the drug bonds with unusually high affinity, thereby activating or blocking this subset with negligible effects at these low doses on most of the receptors.

Are Low Dose Medications the Same As Homeopathic Medicines?

No. Homeopathic medicines have rarely been subject to experimental testing, whereas there is a growing scientific literature on low dose medications. Homeopathy was founded by Samuel Hahnemann in Germany around 1800 (long before any scientific understanding of how highly diluted medications might work and in most cases they had never been shown to work by experiment or careful statistical analyses of patients being treated with them). The field was based upon vague ideas of “like cures like” and the “law of infinitesimals.” A propranolol dose of 1% of the usual is far different than a 1/10,000,000 homeopathic dose.

Naturally, in America, physicians saw homeopathy as competitive to their own sort of medicine, probably just as poorly understood, and fought its intrusion into “their” profession. Still, homeopathy attracted adherents and was able to evade FDA regulations for quite a long time. As an op-ed in the New England Journal of Medicine (Jan 21, 2016) explained: “In 1988, recognizing the increasing size of the homeopathic-drug market, the FDA issued a Compliance Policy Guide mandating conformity with good manufacturing practices and appropriate labeling regarding ingredients and directions for use. Homepathic drugs used for ‘serious’ conditions were to be prescribed by clinicians...” The FDA’s rules provide no informative education for the public, but appear to provide the FDA’s endorsement of homeopathic therapies by permitting them to be sold under FDA rules. All this will accomplish is to make homeopathic medicines more expensive, while increasing the FDA’s powers over the field of medicine. Better if the FDA stayed out of homeopathy altogether.

The article on the FDA’s new heavy handed policies over homeopathic medicine that was published in the Jan. 21, 2016 New England Journal of Medicine, typically for this medical journal, strongly supports the new power of the FDA over a competing branch of medicine. As the article’s last sentence puts it, “[t]he recent actions by the FDA and FTC may finally signal the end of homeopathic drugs’ century long evasion of regulatory scrutiny.” These folks have never seen anything, no matter how harmless or how many people it could help, that they didn’t want to regulate—making it harder to get and much more expensive. As Ronald Reagan described the government’s approach to command-and-control, “If it moves, tax it. If it slows down, keep on taxing it, and if it stops moving, subsidize it.”

References

  • Silverman, Wright, Levitsky. Efficacy of low-dose propranolol in preventing postoperative supraventricular tachyarrhythmias. Ann Surg. 196(2):194-7 (1982).
  • Berkson et al. The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low dose naltrexone protocol. Integr Cancer Ther. 5(1):83-9 (2006).
  • Frech et al. Low-dose naltrexone for pruritus in systemic sclerosis. Int J Rheumatol. 2011:804296. doi: 10.1155/2011/804296. Epub 2011 Sep 12 (2011).
  • Ohgami et al. Lithium levels in drinking water and risk of suicide. Br J Psychiatry. 194:464-5 (2009).
  • Tsaltas et al. Enhancing effects of chronic lithium on memory in the rat. Behav Brain Res. 177:51-60 (2007).
  • Maimaiti et al. Intranasal insulin improves age-related cognitive deficits and reverses electrophysiological correlates of brain aging. J Gerontology A Biol Sci Med Sci. 71(1):30-9 (2016).
  • Fagermoen et al. Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. Bmc Pediatrics. 15:117 (2015).

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