February 2016 Blog with Durk and Sandy

RESISTING METABOLIC DYSFUNCTION WITH RESISTANT STARCH

Resistant Starch—A Neglected Dietary Component

A recent review (Birt, 2013) explains what resistant starch is and how it benefits human health.

The review first notes that resistant starches (of which they describe four different types) improve health by “reduction of colon cancer precursors, systemic regulation of macronutrient [ie, carbohydrates] metabolism, and altered secretion of hormones...” as well as foster gut health largely via the production of butyrate and other short chain fatty acids. (Birt, 2013)

If these benefits aren’t enough, new research shows that resistant starches cause beneficial changes to the colonic microbiota and can also ameliorate the results of vitamin D deficiency (such as is associated with many diseases, including type I diabetes, dementia) (Littlejohns, 2014); and autoimmune, some cancers, type 2 diabetes, cardiovascular disease and infectious disease (Wacker, 2013).

The different types of resistant starch are identified in the review: Type I is found in the endosperm of cereal grains or seeds that are surrounded by protein matrix and cell wall material that interferes with digestion and also, importantly, reduces the glycemic response (just as if you had eaten a low glycemic index meal). Type II is the type found in uncooked potato starch; after cooking this type of resistant starch becomes highly digestible. Type III is characterized by high levels of amylose starch—the type of starch that has fewer branched chains as compared to amylopectin starch, which is easily digested. Type IV is “chemically modified starch” which is likely to be identified on food labels as “modified starch,” which is a natural form of starch that is complexed with a lipid.

See our article on cooking starchy foods with MCT oil and then refrigerating it, which will result in the formation of more resistant starch. [See “New Technology Doesn’t Have to Be Expensive or Complicated”, in the April 2015 issue of Life Extension News.]

As the review explains, [t]he botanical role of starch is to provide plants with a stable reserve of glucose for metabolism.” “Because the amylose component of starch is less branched than amylopectin, high-amylose starch tends to be more resistant to digestion than low-amylose starch.” (Birt, 2013).

It is interesting to know that “foods such as potatoes, rice, pasta, breakfast cereals, and bread are low in resistant starch (<2.5%, dry matter basis). Cooked legumes, peas, and cooked and cooled starchy foods are high in resistant starch (5.0-15%, dry matter basis).” You can continue to enjoy the foods low in resistant starch or not eat foods containing high quantities of resistant starch (if you don’t care for them) by taking resistant starch in the form of a dietary supplement. We take a resistant starch supplement and Durk also cooks his high fiber pasta with MCT oil to increase the Type IV resistant starch his (and sometimes Sandy’s) diet supplies.

Birt, Boylston, Hendrich, et al. Resistant starch: promise for improving human health. Adv Nutr. 4:587-601 (2013).

Littlejohns et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology.83:920-8 (2014).

Wacker and Holick. Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 5:111-148 (2013).

[See “New Technology Doesn’t Have to Be Expensive or Complicated”, in the April 2015 issue of Life Extension News.]

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).

HYDROGEN POWER

Hydrogen Gas Perfuses the Body, Promotes Better Health, By Following the Rules of Chemistry and Physics and NOW... Those of QUANTUM MECHANICS!

We have written earlier [see “Hydrogen Therapy” in the June 2012 issue of Life Enhancement] on the important protective effects of hydrogen gas, produced by fermentation by certain microbes in the gut, by scavenging the highly potent oxidant peroxynitrite as well as damaging hydroxyl radicals.

A new hypothesis proposes that hydrogen tunneling occurs in the enzymes of humans and other animals (Klinman, 2006). This phenomenal new vision points to how hydrogen changes the way enzymes such as alcohol dehydrogenase work. The idea is that “[h]ydrogen, like an electron [can tunnel] through an energy barrier...” The motions of the enzyme [in response to the movement of hydrogen] are critical for the quantum phenomenon to occur. The motions of the enzyme bring two sites, the acceptor and donor that are needed for the reaction to take place, very close together—so close that the hydrogen can move like a wave to get from one site to another.” (Mukhopadhyay, 2016).

This is amazing because, for one thing, hydrogen is 2,000 times heavier than an electron, which is known to tunnel.

The hypothesis is characterized (Mukhopadhyay, 2016): “The emerging picture is a ‘very different view of catalysis’,” says Klinman [Judith Klinman, University of California, Berkeley who, with her colleagues, did this work]. “The role of the whole protein, through these fluctuating conformations, is to bring things so close that quantum mechanics starts to take over, even at room temperature.”

This very new field of science, quantum biology, is sure to open up many new ways of looking at disease. In the case of hydrogen, as much as we now know of its beneficial effects on biological mechanisms, we can look forward to much more that it can do beyond that via the, perhaps, surprising field of quantum mechanics.

What this means is that hydrogen may be doing a great deal more in the body when hydrogen is generated by certain bacteria in the gastrointestinal tract than has been previously understood—for example, scavenging hydroxyl radicals and peroxynitrite. Incidentally, peroxynitrite, a powerful oxidant, has been identified as a key factor in the development of heart failure (Carnicer, 2013), of fibrosis (Daiber, 2013), and in others.

It is interesting to note that hydrogen is, by far, the fastest moving molecule in one’s body, even without the additional boost of enzymatic motions.

References

• Klinman. Linking protein structure and dynamics to catalysis: the role of hydrogen tunneling. Philos Trans R Soc Lond B Biol Sci. 361(1472):1323-31 (2006).
• Mukhopadhyay. Quantum Biology. ASBMB Today. www.asbmb.org/publications. (January 2016).
• Carnicer, et al. Nitric oxide synthases in heart failure. Antioxid Redox Signal.18(9):1078-99 (2013).
• Daiber et al. Protein tyrosine nitration and thiol oxidation by peroxynitrite—strategies to prevent these oxidative modifications. Int J Mol Sci. 14:7542-70 (2013).

Oh No, It Couldn’t Be, Could It??

There Might Be a Basis for PHRENOLOGY in the Histones of DNA

You remember phrenology, right? That was a theory that is now considered bizarre if not outright nuts that the mentality of a person could be determined by the ridges and nooks and crannies of the outer surface of the skull. How could that possibly be? It turns out that HDAC8, histone deacetylase 8, “specifically controls the patterning of the skull. Mutations in the HDAC8 gene are associated with Cornelia de Lange disease, a syndromic form of intellectual disability characterized by facial dysmorphisms.” (Bassett, 2014). In other words, the ridges and nooks and crannies of the skull (the pattern) are partially determined by HDAC8 and, when HDAC8 is mutated, associated with a disease of deficient mentality. Phrenology might have been mostly a lot of hand waving, but there could have been a little grain of truth there, too, buried under a bushel of bad statistics. Histones are protein structures surrounding DNA in the nucleus (but not in mitochondrial DNA) that control access to DNA and, in this way, determine when genes are accessible for expression and when they are not (Bassett, 2014).

Reference

• Bassett and Barnett. The role of dietary histone deacetylases (HDACs) inhibitors in health and disease. Nutrients. 6:4273-4301) 2014).

Oh, no, THIS couldn’t be, could it?

Crumpled Paper As a Model for Cortical Folding in Mammalian Brains

Phrenology is awfully strange and we know of no non-BS scientific papers to go with it.

Here is another view of brain folding that seems pretty weird, too, but researchers have some experimental evidence for their hypothesis.

Scientists have developed a mathematical model for what it looks like when the brain folds and it looks like... crumpled paper (Mota, 2015). The illustration in the commentary (Striedter, 2015) on the study showing the paper ball when crumpled, then expanding into its final folded form has the caption: “Folding increases with paper size, thicker paper has fewer folds. An analogous scaling rule applies to cortical folding in mammalian brains.”

The researchers here “provide a novel mathematical description of how the degree of neocortical folding in mammalian brains varies with other biological parameters, notably cortical thickness and surface area, and they offer the crumpling of a paper ball as a physical model to explain the observed scaling rules.” (Striedter, 2015). “For species with folded cortices (such as the human brain), total surface area increases faster than the exposed surface area (i.e., the slope is substantially greater than 1) [whereas the slope is 1 in species, such as rats and mice, that have smooth cortices].” Interestingly, whales and dolphins have more cortical folds than other mammals with the same cortical surface area (Striedter, 2015).

The researchers (Mota, 2015) crumpled paper balls to determine how the balls relaxed after being crunched. The result was consistent with the general scaling law as seen in the folding neocortex. As the commentary (Striedter, 2015) on the paper notes, “[t]he principal problem with the paper ball analogy is that it describes the folding of a structure that no longer grows, whereas the cortex folds during development.”

References

• Striedter and Srinivasan. Knowing when to fold them. Science. 349:31-2 (2015).
• Mota and Herculano-Houzel. BRAIN STRUCTURE. Cortical folding scales universally with surface area and thickness, not number of neurons. Science. 349:74-7 (2015).

The Benefits of Aged Garlic May Be Somewhat Underestimated

A report from the BBC (30 March 2015) reports the potent effects of some awfully old medicine. A 9th Century Anglo-Saxon remedy for treating eye infections used onion, garlic, and part of a cow’s stomach was found in Bald’s Leechbook, an old English manuscript now held by the British Library. Scientists using this remedy were “astonished” to find that “it almost completely wiped out methicillin-resistant staphylococcus aureus, otherwise known as MRSA.” It is also otherwise known as a deadly killer, with a high mortality rate in humans. The remedy actually killed “up to 90%” of the MRSA bacteria, a phenomenal kill rate compared to what infected humans are currently being treated with in hospitals (where they are frequently infected in the first place).

These findings were said to be presented at the Annual Conference of the Society for General Microbiology in Birmingham, England. (As the conference was to have taken place in 2015, the findings have, presumably, already been presented).

Here is the actual formula for the remedy:

“Equal amounts of garlic and another allium (onion or leek), finely chopped and crushed in a mortar for two minutes.

Add 25 ml. (0.87 fl oz) of English wine [it MUST be English wine]—taken from a historic vineyard near Glastonbury [does this sound like an advert?]

Dissolve bovine salts in distilled water, add and then keep chilled for nine days at 4C.”

The bovine salts probably contained taurine (named after taurus—Latin for cattle—where is was first discovered). Taurine and chloride or bromide can be converted in one’s body to the powerful antimicrobials taurine chloramine and taurine bromamine, which are also anti-inflammatory molecules. [See “New Taurine & Bromine Formulation” in the September 2014 issue of Life Enhancement.]

The wine contained polyphenols with antimicrobial properties and garlic also has such properties.

That’s one way to look at it...

Being Short Can Be An Advantage

“The shorter you are, the longer you’ll live if you’re a Japanese man, Hawaii-based researches concluded.”

“A study based on the Kuakini Honolulu Asia Aging Study showed shorter men were likelier to have a protective form of the longevity gene FOXO3, leading to smaller body size in early development and a longer lifespan. Shorter men were also likelier to have lower blood insulin levels and less cancer.”

—reported in the May 7 2014 PLoS ONE

Recipe

Sandy’s Delicious Carbonated Orange Juice

Like carbonation in your orange drink? You don’t have to buy somebody’s not very tasty orange soda. Make your own. It’s SO easy and tastes GREAT.

All you need is about two cups of orange juice, fresh squeezed for best flavor but if you’re in a rush, a good quality commercial orange juice will do fine. You add about 1/4-1/2 teaspoon of baking soda to the juice (depending on how much carbonation you want) and stir briskly (maybe 20 seconds) until you see some fizz at the surface. Then drink it for a treat compared to plain OJ.

The small amount of baking soda (sodium bicarbonate) you’ve added to the orange juice will have NO effect on the flavor, but the bubbles from the carbonation will produce a nice tingling sensation on your tongue. You can do it with any fruit juice that is acidic, like pineapple juice.

Watch out for overflowing foam when you add the baking soda!

How to Detect Lies With a Storytelling Technique

A hypothesis put forth by Andy Morgan, a forensic psychologist at Yale University who specializes in human memory and deception, purports to show that one can detect lies from analyzing stories subjects wrote about experiences they’d had. Morgan calls this “cognitive interviewing” and believes that the physical signs that are usually considered possible indications of lying such as blood pressure and respiration changes, alterations in skin such as sweating only achieves an accuracy of about 50% or, as he puts it, like flipping a coin.

What Morgan and his colleagues found, in interviewing 1200 people, was that stories describing the physical/sensory events in their experiences became much harder to put together when they were coming from liars. Morgan produced transcripts of each interview and showed that in nearly 85% of cases, “the transcripts that contained fewer unique words and fewer words overall related to the stories told by liars.” Morgan believes that this is because having to make stuff up reduces the richness of what is being said and the complexity of the language used to describe it.

This was reported in Criminal (podcast) episode 2—“Pants on Fire,” 14 February 2014