May 2015 Blog with Durk and Sandy

APPETIZERS

“Man is so made that he can only find relaxation from one kind of labor by taking up another.”

— Anatole France, The Crime of Sylvestre Bonnard

“You seem ... to consider the judges as the ultimate arbiters of all constitutional questions; a very dangerous doctrine indeed, and one which would place us under the despotism of an oligarchy ... The Constitution has erected no such single tribunal.”

— Thomas Jefferson, 1820

“One man with courage is a majority.”

— Thomas Jefferson

“Quemadmoeum gladis nemeinum occidit, occidentis telum est. (“A sword is never a killer, it’s a tool in the killer’s hands.”)

— Lucius Anaeus Seneca (“the younger” ca. 4BC - 65 AD)

“Among the many misdeeds of the British rule in India, history will look upon the act of depriving a whole nation of arms, as the blackest.”

— Mahatma Gandhi

(D&S Comment: A very interesting take on the bad deeds of English rule in India by Gandhi. “History” doesn’t yet seem to have come to this view yet. Only in America do we still have sufficiently strong popular support for the right to keep and bear arms that this statement by Gandhi could be understood.)

“Just because you do not take an interest in politics doesn’t mean politics won’t take an interest in you.”

— Pericles (430 BC)

“Politics is the art of looking for trouble, finding it whether it exists or not, diagnosing it incorrectly, and applying the wrong remedy.”

— Ernest Benn

“Remind me,” Jubal told her, “to write an article on the compulsive reading of news. The theme will be that most neuroses can be traced to the unhealthy habit of wallowing in the troubles of five billion strangers.”

— Robert A. Heinlein Stranger in a Strange Land, (1961)

The Size of the Sun

“It is immeasurably huge. This you can tell from the following observation. Trees which are planted at the far limits of East and West, nevertheless cast shadows of the same proportions—though these trees are miles and miles apart, the sun appears in the same place, as though centred on either one.”

— Pliny the Elder, Natural History

DID YOU KNOW . . . 

Cumulative Use of Strong Anticholinergics May Be Associated with An Increased Risk of DEMENTIA

A new paper¹ just published in JAMA INTERN MED reports that, among a cohort population of 3434 men and women aged 65 or older with no signs of dementia at the start of the study, during a mean followup of 7.3 years, higher cumulative use of anticholinergic drugs was associated with an increased risk of DEMENTIA. Anticholinergic drugs are used as, for example, antispasmodics for the gastrointestinal tract, antimuscarinics for the bladder (“overactive bladder”) and antiparkinsonians. The paper notes that the use of anticholinergics in older adults ranges from 8% to 37%.

During the 7.3 years of mean followup, 797 participants (23.2%) developed dementia, with 637 of these reported to develop Alzheimer’s disease. There was a 10 year cumulative dose-response relationship observed for both dementia and Alzheimer’s disease, that is, the higher the cumulative dose used during that period, the greater the likelihood of developing dementia and Alzheimer’s disease.

Though this was an association, not proof of cause and effect, it is important to keep in mind that Alzheimer’s disease and dementia are both positively linked to dysfunction in the cholinergic nervous system in the brain. Hence, this association is likely (but not proven) to be a causative one.

Use It Or Lose It

The relationship between the cholinergic nervous system in the brain and cognitive aging has been a hot research subject for at least the past 40 years.² In an important 1974 paper,² for example, the authors say: “The cognitive and memory disturbances occurring with aging may reflect some relatively specific disorder of cholinergic neurotransmitter function — such as impaired synthesis, release or receptor iuptake of acetylcholine — that is largely reproduced by pharmacologic cholinergic blockade.” The paper² itself was a test of anticholinergic drugs in young subjects and showed memory/cognitive impairment. The authors conclude that their data “raise the interesting association between cholinergic blockade and the mental deterioration of aging, however, and suggest the need for further study of the integrity of the cholinergic pharmacosystem in the elderly.”

Declining Ability of the Older Brain to Transport Choline Across the Blood-Brain Barrier

We have written extensively about the markedly decreasing ability of the human brain, as it ages, to import choline across the blood-brain-barrier into the brain from the general circulation. [See “Maintain your Brain the Durk Pearson & Sandy Shaw Way” in the March 2004 issue.]

Moreover, in the explanatory material in the paper,¹ the authors note that, while “the general view is that anticholinergic-induced cognitive impairment is reversible on discontinuation of medication therapy,” “several investigators have reported that anticholinergics may be associated with an increased risk for sustained cognitive deficits, such as mild cognitive impairment or dementia.” The authors suggest that a plausible biological mechanism for these findings is that “cumulative use of these agents results in pathologic changes in the brain similar to those observed with Alzheimer’s disease (AD).”

All of the first generation and many of the second generation antihistamines have anticholinergic effects, though not the third generation. One way to tell is if the antihistamine you use causes your mouth to become dry, it likely has anticholinergic activity.

References

1. Gray, Anderson, Dublin, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 175(3):401 – 7 (2015).
2. David A. Drachman, Janet Leavitt. Human memory and the cholinergic system. Arch Neurol. 30:113 – 21 (Feb. 1974).

REALLY Low Dose Lithium Stabilizes Alzheimer’s 
Disease Patient Cognition Over 15 Months

A group of scientists, concerned about increased toxicity of lithium in the aged at the usual dosages used therapeutically (for bipolar disorder, for example), ranging from 150 to 600 mg daily, as a result of reduced glomerular filtration in the kidney, among other things, decided to do a study on Alzheimer’s patients at a truly tiny dose, 300 micrograms once a day.¹ Well water in areas with higher than usual amounts of lithium may contain that much lithium and commercially-available premium priced mineral waters from some springs and artesian wells often contain water with prized increased amounts of lithium, highly sought after by many looking for the healthful benefits of the mineral at low doses. See next section below for more on lithium in natural sources of water.

The 113 patients included in the study had their mental states evaluated every three months using MMSE (mini-mental state examination) applied in a double-blinded manner at the hospital (the physicians, patients, family, and caregivers did not know which patients received lithium and which received placebo). The MMSE is designed to measure the ability of a person to function doing normal everyday tasks.

During the study, those receiving microdose lithium showed no decrease in performance on the MMSE, whereas the control group (receiving no lithium) had decreasing scores, indicating cognitive decline. The authors note that relying just on the MMSE was a limitation of the study, as it does not give a complete picture for the determination of the assumption of homogeneity between the groups, though they did administer two other statistical tests to verify the homogeneity between groups, the Friedman non-parametric test followed by the Bonferroni test.

The results of this study, using a dose so small and registering a stabilization of the AD patients over such a long period, 15 months, is remarkable and is a worthy subject for determination of the mechanisms involved.

We note that this amount of lithium per day is so small that even our own low dose lithium contains 6 mg in a daily capsule. We based this dose on the amount of lithium you could get from drinking a reasonable amount of famous European health spa mineral water naturally high in lithium sold legally in the United States. The 6 mg dose is 6000 micrograms, 20 times as much as in the 300 microgram microdose used in this Alzheimer disease study.¹

Reference

1. Nunes, Viel, Buck. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Curr Alzheimer Res. 10:104 – 7 (2013).

Lower Dose Lithium Protects Against Amnestic Mild Cognitive Impairment in Human Study Possible Mechanism Identified

A small-randomized controlled study of 45 individuals with mild memory impairment received lithium (150 mg a day titrated to serum levels of 0.25 – 0.5 mmol/l, a range lower than the usual dosage used to treat bipolar disorder) or placebo over 12 months. Lithium treatment was associated with a significant decrease in cerebrospinal fluid concentrations of p-TAU (p=0.03) and better performance on the cognitive subscale of the Alzheimer’s disease Assessment Scale and in attention tasks.^1A

The most interesting datum mentioned in the paper was that preliminary data from the lab that performed the study1A described above (data said to be available upon request) showed that lithium treatment in the dose range used in the above study for two weeks in healthy volunteers caused a 50% reduction in GSK3B activity in leukocytes. Although this enzyme is known to be inhibited by lithium at therapeutic doses (those used to treat bipolar disorder) and is thought to be a major mechanism of its action at those doses, this is the first time we’ve seen a measurement at lower doses of lithium. This might suggest that even lower doses of lithium may have an inhibiting effect on the enzyme, though it might be inhibited less than at the higher doses depending on the shape of the dose-response curve.

References

1A. Forlenza, Diniz, Radanovic, et al. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 198:351 – 356 (2011).

LITHIUM AS AN ESSENTIAL NUTRIENT

A 2012 paper² provided detailed information on the presence of lithium in drinking water and vegetation and on its essentiality in a large number of animal and human studies.

The review reported that there is a wide variation in the amount of lithium found in drinking water, spring water, spa water and bottled water. One study of 132 brands of bottled water from 28 countries found lithium concentrations ranging over 5 orders of magnitude (from 0.057 to 5,460 μ/l. “Li concentrations of 8.7 mg/l and of >9 mg/l have been reported for the Friedrich-Quelle, a famous spring in Baden-Baden/Germany, and for the spa water in Pompeya/Argentina, respectively.”²

“The long-term consumption of low-Li drinking water is regarded as a risk factor for higher incidences of suicides, homicides, and crimes as shown in several studies. For example, in 24 counties in Texas/USA with a total population of 6 million (>60% of the state population), during a 2-year study (1967 – 1969), a significantly inverse relationship between (1) Li concentration of local drinking water, (2) Li concentrations of the urine among the respective residents, and (3) mean annual rainfall amounts in the respective county sites and (1) state mental hospital admission rates, (2) admitting rates for four major mental disorders (psychosis, neurosis, schizophrenia, personality problems), (3) homicide rates, and (4) road distance from resident county to nearest state mental hospital was found (p≤0.05 to <–0.001). The Li levels in drinking water were classified into 4 groups: <11.0; 11.0 – 29.9, 30.0 – 69.9; >70.0 μg/l.”¹

A second study reported in the review² included 27 counties and lasted for 10 years (1978 – 1987) and found that that the incidence rates of suicide, homicide, and rape were significantly higher in counties whose drinking water contained low (0–12 μg/l) and medium (13–60 μg/l) lithium concentrations than in counties whose drinking water had high Li concentrations (79 – 160 μg/l)(p<0.01). They also found associations with the rates of robbery, burglary, and theft significant at p<0.05. These are really remarkable differences that suggest improved mental function with low dose lithium.

On the basis of these and many other studies, the basic requirement of lithium in humans has been assessed at 1 μg/kg body weight/d in humans derived from intake data in Germany, thus, the lithium requirement for an adult of 70 kg body weight would be 70 μg/d. In another assessment study, Schrauzer suggested a provisional recommended dietary allowance (RDA) of 1 mg lithium/day for an adult of 70 kg body weight.³

References

2. Evaluation of beneficial and adverse effects on plants and animals following lithium deficiency and supplementation, and on humans following lithium treatment of mood disorders. Trace Elem Electrolytes. 29(2):91-112 (2012). 
3. Schrauzer. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 21:14-21 (2002).

Lithium at Therapeutic Doses Protects Neurons Robustly Against NMDA-induced Excitotoxicity

In another study,⁴ lithium at therapeutic doses in cultured cerebellar granule cells from 8 day old Sprague Dawley rats pretreated with lithium chloride for 6 – 7 days and then exposed to 100 μM of glutamate for 24 hours. Preincubation of the cultures with 2mM lithium chloride for 7 days markedly protected the neurons against glutamate-induced excitotoxicity. Although significant protection was detected at 0.5 μM lithium, the maximal effect detected in this study occurred at 3 μM.

Of course, the therapeutic dose of lithium is far higher than that in commercially available high lithium containing mineral water or tap water with naturally high levels of lithium. We are stunned by the findings reported in the study above of protection against cognitive decline in AD patients over 15 months from only 300 μg per day.

Also, see Will Block’s review of other papers on lithium in brain health ( “Can Lithium Benefit Brain Health?” in the June 2004 issue of Life Enhancement.)

References

1. Nunes, Viel, and Buck. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Curr Alzheimer Res. 10:104 – 7 (2013). 
4. Nonaka, Hough, Chuang. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. Proc Natl Acad Sci U S A. 95:2642 – 47 (March 1998).

Lithium, an Essential Nutrient, Has Neuroprotective Effects at Low Dosage

Lithium salts act as a drug at high doses, but act as a neurologically beneficial essential nutrient at much much smaller amounts.

First, a brief description of the very high dose medical use of lithium — it can be effective as a drug treatment for manic-depressive (or bipolar) illness. It provides nearly complete protection against attacks in about 1⁄3 of bipolar patients, improved symptoms in another 1⁄3, and is ineffective in the remaining 1⁄3.^A However, the treatment of bipolar illness requires high doses of lithium, close to the toxic dose. The clinically effective dose range is 0.6 – 1.0 μM serum level, while the toxic level begins at about 1.2 μM or greater. Symptoms in the dose range of 1.2  –  2.0 μM are said to be usually mild and to seldom cause death or permanent neurological damage.¹ Lithium is excreted via the kidneys or in sweat. Because the toxic dose is not much higher than the therapeutic dose and because prolonged exposure to serum levels of 2μM or greater may cause liver and kidney damage,¹ though, it is necessary for those receiving pharmacological doses for bipolar disorder to receive periodic blood tests to ensure the lithium blood levels remain in the therapeutic range and that liver and kidney functions remain normal.

What is more interesting to us than its use at the highest level that is tolerable before toxic effects ensue is what lithium does at low doses, a dose so low that it would NOT be an effective treatment for bipolar disorder and, hence, the mechanisms of its actions may differ from those that take place at a high dose. It is particularly interesting in light of the fact that, as mentioned above, lithium at small amounts has been found to be an essential mineral with a suggested RDA of 1 mg/day for a 70 kg adult human.

Lithium in Spring Water Reported to Be Positively and Significantly Associated with Brain-Derived Neurotrophic Factor

Brain-derived neurotrophic factor (BDNF) is an important growth factor involved in many cognitive processes including learning and memory, emotional processes, and sometimes psychopathological conditions such as addiction. The effect depends on the specific tissue in which the BDNF is released, the conditions under which it is released, and the dosage released.

In a study of 43 Japanese subjects who did not have psychiatric dysfunction, the participants drank 3.64 liters of spring water from two springs, one of which contained 6.1 mg/liter of lithium and the other contained 15.7 mg/liter, much lower than lithium in clinical use (900 to 1800 mg/day of lithium carbonate, containing 170 – 340 mg lithium/day) but at much higher levels than generally contained in lithium-containing tap water (generally much less than 1 mg/liter). Their serum lithium levels increased from 0.026 to 0.073 mEq/L, a much lower level than if they had been treated with bipolar treatment levels of lithium. The results of a Profile of Mood States indicated that most ratings were significantly improved (though whether this was caused by lithium is unclear  —  the authors suggested it could possibly be a placebo effect). More interestingly, however, serum lithium levels were significantly and positively associated with BDNF levels. BDNF was also negatively and significantly associated with changes in the State-Trait of Anxiety Inventory scores. The researchers cited an earlier study in which lithium had been reported to increase BDNF levels. As this^B was a small open (no blinding, no placebo control) study, the authors rightly noted that further studies are needed to confirm these findings.

German studies have reported the effects of lithium-deficient diets in animals such as goats, pigs, cattle, broiler chickens, and rats.^C For example, one such study of a 13 year investigation with lithium-deficient goats reported that 41% of the lithium-deficient goats but only 7% of the controls (lithium adequate) died during the first experimental year indicating a highly significant difference (p<0.001) between the groups. Moreover, by the end of the third experimental year, all lithium-deficient goats had died, but 18% of the controls were still alive.^C

The same paper^C also described the analyses of various types of bottled water that included spring water, mineral waters, etc. from 28 countries finding that natural lithium concentration varied over 5 orders of magnitude, from 0.057 to 5,460 mg/l. The waters of the Friedrich-Quelle, a famous curative spring in Baden-Baden, Germany, were reported to be 8.7 mg/l. The upper crust of European society visits there for restorative effects. While there, visitors are encouraged to drink only the spring water.

Few data are available on what mechanisms are operative at the very low doses of lithium (except possibly for an increase in BDNF, as discussed above) as compared to mechanisms that help explain the therapeutic effects of high dose lithium in the treatment of bipolar disorder. Lithium has been reported to inhibit phosphatases in both plant and animal cells but we didn’t find any specific data on how this might be involved in (for example) suicide or homicide rates.

Lithium is reported to have a small ionic radius that results in lithium having the highest electronegativity and strongest polarization power among all alkali metal ions and is said to have a relatively large stable radius of the hydrated ion.^C The implications of all this obviously bears upon its biological effects. We await with great interest an elaboration of the effects of lithium that provide mechanistic data explaining its biological properties. In the meantime, lithium is an essential nutrient, appears safe to use at low doses, is very inexpensive, and is available without a prescription!

References

A. Young. Review of lithium effects on brain and blood. Cell Transplant. 18:951 – 75 (2009). 
B. Shiotsuki et al. Drinking spring water and lithium absorption: a preliminary study. German J Psychiatry. 11:103 – 6 (2008). 
C. Schafer. Evaluation of beneficial and adverse effects on plants and animals following lithium deficiency and supplementation, and on humans following lithium treatment of mood disorders. Trace Elem Electrolytes. 29(2):91 – 112 (2012).

Possible Life Extending Effects of Low Dose Lithium

A large epidemiological study^D has reported that there was an inverse correlation between drinking water lithium concentrations and all-cause mortality in 18 neighboring Japanese municipalities with a total population of 1,206,174 people. The researchers also found that, lithium chloride at a similar dose to that ingested by the humans in their drinking water, extended lifespan in C. elegans.^D

The authors^D adjusted the mortality data for suicide rates (as higher levels that would still be considered low dose lithium has already been found to be associated with reduced suicide rate) and found that overall mortality rate was still inversely associated with tap water lithium levels. In the roundworm Caenorhabditis elegans, mortality in populations exposed to 10 μM of lithium chloride was reduced, while roundworms exposed to 1 μM of lithium chloride showed no effect on mortality rate. These results are consistent with a possible life extending effect of low dose lithium. A dose of 6 mg/day of lithium for an adult human is higher than the lithium level found to be effective in the roundworms.

Chronic Supplementation with Low Dose Lithium May Protect Against Ischemic Damage as Occurs in Stroke

A further study of low dose lithium^E reports neuroprotective effects in a rat model of ischemia (inducing ischemia by middle cerebral artery occlusion for 90 minutes followed by reperfusion). The experimental animals received lithium at 1 mmol/kg (given subcutaneously) for 14 days prior to middle cerebral artery occlusion and then 2 days following. Lithium chloride significantly reduced the infarct volume (number of cells killed by the procedure) by 32.7% compared to the animals receiving vehicle containing no lithium. The chronic treatment with low-dose lithium increased the expression of the antiapoptotic protein Bcl-2 and reduced the expression of the apoptotic-inducing proteins p53 and Bax. The low dosage administered to the experimental animals here was about six times higher than would be ingested from a single serving of our lithium capsules (6 mg per cap).

References

D. Zarse et al. Low-dose lithium uptake promotes longevity in humans and metazoans,” Eur J Nutr. 50:387 – 389 (2011). 
E. Xu et al. Chronic treatment with a low dose of lithium protects the brain against ischemic injury by reducing apoptotic death,” Stroke. 34:1287 – 1292 (2003).

Neuroprotective Effects of Chronic Low Dose Lithium in Traumatic Brain Injury in Mice

Considering the high number of automobile accidents and falls resulting in injury or death in the U.S. every year, it would be expected that many incidents of traumatic brain injury occur. The sequelae of such injuries may take place over a period of time and may not receive timely or adequate treatment to prevent temporary (or even permanent) cognitive dysfunction. It is of considerable interest, therefore, to find that, as reported in a recent paper,^F chronic low dose lithium can provide substantial protective effects against a negative outcome in traumatic brain injuries, at least as demonstrated in a mouse model. Since the mechanisms responsible for the damaging effects of such injuries are very similar for mice and men, we consider low dose lithium to be plausibly protective against brain damage, as could occur in a car accident or a fall.

SIDEBAR: In fact, falls are becoming much more common as the population ages and can result in considerable disability or even death as a result of brain damage. Sandy’s mother and father both died as a result of falls, so even at 85 (her mother) and 91 (her father) they might have lived on for years had they not fallen. Her mother died of a neck fracture after falling, while her father died of a stroke resulting from brain damage induced by a fall. We reported earlier (in Vol. 6 No. 3 of the June 2003 issue of this newsletter) the results of a human clinical trial of 122 elderly women in a geriatric long-stay care facility, that receiving 1200 mg calcium plus 800 IU of cholecalciferol (vitamin D) per day over 12 weeks resulted in 49% reduction in falls as compared to calcium alone!*

As the authors of the paper explain, the initial mechanical damage in traumatic brain injury results in blood-brain barrier disruption, cerebral edema, and subsequent increase in intracranial pressure. Later, the secondary effects emerge as a result of an inflammatory response with the release of pro-inflammatory cytokines and the subsequent death of neurons. Cognitive deficits may linger.

The mice were treated daily for 2 weeks with 1 mmol/kg of lithium chloride by intraperitoneal injection and then, under deep anesthesia, were subject to a “controlled cortical impact” to simulate the result of an accidental traumatic brain injury. The researchers found that the animals receiving low dose lithium had significant reduction of loss of hemispheric brain tissue and lesion volume as compared to saline treated controls also subject to traumatic brain injury but receiving no lithium. Low dose lithium also attenuated the learning and memory deficits resulting from the experimental brain injury (as assessed by how long it took the animals to find the hidden platform in the Morris Water Maze).

The authors^F conclude that “[t]aken as a whole, these observations suggest lithium may be a beneficial ‘preventive’ therapeutic approach for reducing the neuronal degeneration and related behavioral dysfunction associated with neurodegenerative illnesses.”

We are personally aware of the extent of cognitive deficits that can ensue following a vehicular accident as a result of what happened to a longtime dear friend of ours. She had been involved in a serious accident while riding a bus and has never been the same since then, a few years later. Since we knew her well before the accident, the changes were very clear to us, that she has problems now with learning and memory that she didn’t have before and overall a substantial decline in her quality of life. She constantly needs reminding of things, even while keeping extensive lists to try to remember. We don’t know how much of this could have been prevented by regular low dose lithium taken before the accident, but we certainly wish she’d had the chance to find out.

Reference

F. Zhu et al. Neuroprotective effect and cognitive outcome of chronic lithium on traumatic brain injury in mice. Brain Res Bull. 83:272 – 7 (2010). 
* Bischoff et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 18(2):343 – 51 (2003).

Daily Injections of Low Dose Lithium for 14 or 28 Days in Wistar Mice Resulted in Increased Size of Neurons and a Denser Dendrite Network

Finally, a paper partly in French and partly in English reported interesting effects of low dose lithium (80 ng/kg lithium carbonate) in the brain cortex of mice: larger neurons and a denser dendrite network.^G These changes remind us of those observed (via fMRI) in the brains of humans receiving lithium at therapeutic levels for bipolar disorder, where brain grey matter volume is increased after 4 weeks of treatment. The increased volume (about 3%) was observed in 8 out of the 10 patients studied.^H

 G. Neiri et al. Effects of low doses of Li carbonate injected into mice. Functional changes in kidney seem to be related to the oxidative status. C R Biol. 331:23 – 31 (2008). 
H. Moore et al. Lithium-induced increase in human brain grey matter. The Lancet. 356:1241 – 2 (2000).

Here’s To Your Health With Beer, the Drink Recommended by Benjamin Franklin!

New and very convincing evidence for the health benefits of moderate drinking of beer appears in a recent paper.¹ Read it just before you take that nice cold one out of your refrigerator and feel the goodness as it passes into your gastrointestinal tract in the service of your health. Have another cold one if you like. Then have a nice day!

If you recall, Benjamin Franklin was the Founder who expressed a wish to have his body preserved in a vat of wine for later revival to see how the U.S. fared. Perhaps, had he known the results of this study, he might have considered being preserved in a vat of beer.

In this study,¹ researchers investigated whether moderate drinking of beer would provide protection against coronary artery disease. The lucky (well, not so lucky because they had induced heart attacks and were later “sacrificed” for the purpose of examining their heart and other organs) participants were 30 month old commercial female pigs weighing about 35 kg, who were randomly distributed to receive during 10 days, a Western hypercholesterolemic diet, same diet + low beer intake (12.5 g alcohol/day; about 1 bottle/day), same diet plus moderate beer intake (25 g alcohol/day; about 2 bottles/day) or the same diet + alcohol-free moderate beer intake (same amount of beer as the moderate beer intake but without alcohol). All groups contained 7 pigs except for the group receiving only the Western hypercholesterolemic diet (no beer), which contained 9 pigs. This is a particularly interesting study for the use of pigs as subjects. Pigs have a gastrointestinal tract very much like humans (both are omnivores) but are not usually used as subjects in nutritional studies because pigs cost a lot more than rats or mice do. The pigs received their beer split into two portions, taken in the morning and in the evening with their chow.

All the animals were, after ten days on the diet plus beer, subject to a process whereby, under anesthesia, they had a heart attack induced by 90 minutes of total balloon occlusion of the mid-left anterior descending coronary artery. Then, 21 days after this induced heart attack, the animals were all killed for examination.

RESULTS: First, there were no deaths among the pigs receiving beer, while two control animals died from refractory ventricular fibrillation during the induction of the heart attack.

2. ARRYTHMIA  —  Animals required cardioversion after the induced heart attack to control arrhythmia. Cardioversion was required in 6 out of 7 survivors of the control Western diet group, 5 out of 7 of the diet + alcohol-free moderate beer, 2 out of 7 in the diet + low beer intake, and 1 out of 7 in the diet + moderate beer intake group.

3. REDUCED SCAR FORMATION  —  The scar size was significantly lower (about 50% less) in the alcohol-beer fed animals as compared to the Western diet only control group. There was a trend toward reduction in the animals receiving alcohol free moderate beer, which did not reach significance.

4. GENETIC CHANGES  —  All beer-fed animals were reported to have an almost twofold increase of Sirt-1 gene expression (reflecting a protective effect against cell death) and a six-fold decrease in active caspase-3 (reflecting reduced cellular apoptosis) in the ischemic cardiac region.

5. CHANGES IN COLLAGEN DEPOSITION IN SCAR TISSUE  —  Matrix metalloprotease 9 (MMP9) activity was fourfold decreased in the beer-fed animals. This reflects a favorable change in the deposition of collagen in scar tissue, with a reparative level induced but excessive fibrosis reduced by the lower level of MMP9.

6. IMPROVEMENT OF HEART PERFORMANCE  —  “... both intergroup and intra-animal analysis revealed a significant improvement in global cardiac performance (LVEF) in beer-fed animals as compared to HC [Westernized hypercholesterolemic diet] controls.¹

7. INCREASED HDL ANTIOXIDANT CAPACITY  —  Beer intake improved HDL antioxidant potential and, in fact, the HDL from beer-fed animals continued to have protective activity against LDL oxidation. The same authors reported observing that moderate (25 g alcohol/day) and regular beer intake for 31 days was associated with an increase in HDL plasma levels.

8. BEER-INDUCED ACTIVATION OF CARDIAC AMPK AND ITS DOWNSTREAM EFFECTOR eNOS —  The researchers suggested that these effects, also observed in the pig beer study¹ may have contributed to the protection seen in the infarcted myocardium.

These are very impressive results. It is nice to know that that nice cold beer waiting for you at home in your refrigerator supplies you with such a terrific package of benefits for your health. (The subjects in this study were female pigs; we would expect similar but not necessarily exactly the same beneficial effects in male pigs. We would also expect similar benefits in humans.)

Reference

1. Vilahur, Casani, et al. Intake of fermented beverages protect against acute myocardial injury: target organ cardiac effects and vasculoprotective effects. Basic Res Cardiol. 107:291 (2012).

ALL NATURAL ANTIMICROBIAL IN FOOD PRESERVATION 

Killing Food-borne Pathogens with Liquid Smoke Estimated Episodes of Foodborne Illness in the U.S.

Two lengthy recent review papers^1,2 on foodborne illness report that each year 31 major pathogens caused an estimated 9.4 million episodes of foodborne illness, with 55,961 hospitalizations and 1,351 deaths. In addition to that, there were another 38.4 million estimated episodes (90% credible interval 19.8 to 61.2 million) of domestically derived foodborne illnesses caused by unknown or unspecified agents, resulting in another 71,878 hospitalizations. When you include known agents not known to be transmitted in food and microbes, chemicals, or other substances in food that might transmit disease, you end up with even more. Clearly, the burden on stricken individuals and overall social costs of these illnesses are immense. Data were derived from multiple sources. For example, the authors¹ estimated total deaths caused by acute gastroenteritis by using multiple cause-of-death data from the National Vital Statistics System (2000 – 2006).

Liquid Smoke As An All-Natural Antimicrobial for Preventing Foodborne Illness

In addition to adding a very pleasant taste and aroma to food at appropriate concentrations, liquid smoke is reported³ to be an effective way to kill many common foodborne pathogens.

Liquid smoke is made commercially by condensing smoke from various types of wood (as chips or sawdust) using a controlled process of minimal oxygen pyrolysis. The gases released in the process are chilled in condensers, which liquefies them. Then the liquid smoke is forced through refining vats and filtered to remove toxic and carcinogenic impurities such as polynuclear aromatic hydrocarbons (PAH). The paper³reports that although PAH are highly toxic, they also have very low water solubility allowing for relatively easy removal by liquid smoke manufacturers.

Different types of wood result in liquid smoke with varying degrees of microbicidal activity against particular pathogens. There were a lot of details³ concerning the use of liquid smoke to treat various types of food. Incorporating liquid smoke in a food product such as frankfurters at 2.5%, 5%, or 10% wt/wt in Zesti Smoke, a branded liquid smoke, suppressed the growth of Listeria but at 10% liquid smoke sensory taste panels rated the frankfurters as somewhat less acceptable than lower concentrations of liquid smoke. The treatment of meats (by infusing them with liquid smoke, for example) intended to be frozen for a period of time appears to be the most likely use by consumers as exposure of the food to the liquid smoke for an extended period would appear necessary to get the microbicidal effects. Generally cooking meat to a high enough temperature would eliminate the need for microbicides, but it is probably more common than not for consumers to fail to use a thermometer to ensure reaching an adequate temperature for a long enough period of time to eliminate the microbes.

References

1. Scallan et al. Foodborne illness acquired in the United States  —  Unspecified agents. Emerg Infect Dis. 17(1):16 – 22 (2011).
2. Scallan et al. Foodborne illness acquired in the United States  —  Major pathogens. Emerg Infect Dis. 17(1):7 – 15 (2011).
3. Lingbeck et al. Functionality of liquid smoke as an all-natural antimicrobial in food preservation. Meat Sci. 97:197 – 206 (2014).

Weight and the Perception of Sexual Attractiveness

People are rightfully concerned about their weight and body composition, especially lean vs. fat tissue weight, as it relates to health. But we wonder how many women would be even more interested in how men perceived their sexual attractiveness from the point of view of their body shape and weight. (Men might be interested in how women — or other men — perceived their sexual attractiveness based on similar considerations, but we have data just on the perception of attractiveness of women by men.)

The data come from an interesting little study published in the Aug. 15, 1998 The Lancet.¹

The first consideration is that, from the point of view of reproductive potential, we would expect that the more fertile a woman’s build appears to be, the more likely she is to appear sexually attractive to a man. Therefore, the researchers began with an impression that the waist/hip ratio would be of particular importance for sexual attractiveness, with a ratio of 0.7 (curvaceous) being the most attractive waist/hip ratio for a woman.

The researchers, therefore, gave 40 male undergraduates color frontal views of 50 women to rate for sexual attractiveness. They then drew ten women from each of the body-mass index categories: emaciated (<15 kg/m²), underweight (15 – 19 kg/m², normal (20 – 24 kg/m², overweight (25 – 30 kg/m²) and obese (>30 kg/m²). Within each of the body mass index categories the women had different waist/hip ratios, typically ranging from 0.68 to 0.90. The sexual attractiveness ratings were significantly explained by body-mass index and waist/hip ratio, but the magnitude of the effect differed strikingly and perhaps surprisingly. Body-mass index accounted for 73.5% of variance, whereas waist/hip ratio accounted for only 1.8%. In this particular study, body-mass index came out by far as the most important factor in determining sexual attractiveness, with the authors rating it as a good predictor of health and reproductive potential.

The curve for attractiveness rating vs. body-mass index showed a peak at about 21 kg/m².

Even the “bust/hip” ratio (hourglass figure) did not contribute significantly to attractiveness ratings more than body-mass index and waist/hip ratio alone.

Reference

1. Tovee, Reinhardt, et al. Optimum body-mass index and maximum sexual attractiveness. The Lancet. 352:548 (1998).

Dip In Affluent Consumers’ Spending in 4th Quarter of 2014 
Shows Sharp Drop in Confidence Among the Most Well-Off

You do hear a lot of lies these days about how well the economy is doing, mostly from the government and those who’d like you to think that higher taxes and more government spending is a great idea. Here are some numbers to help provide some perspective.

Unity Marketing conducted a survey from Oct. 9 – 15, 2014 among 1,330 affluents, which includes those with household income of $100,000 and above. The survey showed a drop in affluent consumer confidence of 12.3 points to 46.4, the lowest mood since Quarter 4 of 2008 to Quarter 1 of 2009. Since the affluent households represent only 20% of U.S. households (24.5 million out of 122.5 million) but account for more than 40% of all consumer spending, this is a very major decrease. The demographics of this survey sample was an average income of $259,000 and average age of 47.9 years.

The sort of goods and services surveyed include art galleries, craft stores, home stores such as Restoration Hardware, Crate & Barrel, IKEA, fashion and clothing, jewelry, and general merchandise such as Macy’s, Target, Costco, Bloomingdale, JC Penney’s. This is the sort of marketing survey conducted to help companies follow the sales of products they offer or are thinking of offering, not a survey for the general public. The purpose of the survey is not political, e.g. to point fingers at anybody, but to help marketers decide what is selling and who is buying.

Reference

1. Danziger. Five Luxe Trends for 2015. Luxury Consumption Index. Unity Marketing.http://www.unitymarketingonline.com/ cms/uploads/white_papers/five_key_luxury_market_trends_final_new.pdf. Accessed April 30, 2015.

NEW EXECUTIVE ORDER ISSUED ON APRIL 1ST IS NO JOKE BUT MAYBE THAT’S WHAT THEY HOPED YOU’D THINK

This Executive Order was issued on April 1, 2015 under the authority of the International Emergency Economic Powers Act (50 U.S.C. 1701 et seq.) (IEEPA), the National Emergencies Act (50 U.S.C. 1601 et seq.) (NEA), Section 212(f) of the Immigration and Nationality Act of 1952 (8 U.S.C. 1182(f), and Section 301 of Title 3, United States Code. Durk checked this by going to the White House website and verified that it was NOT an April Fools Day joke but a bona fide dangerous ukase emanating officially from the 21st century czar in the White House.

Oh no! Not another disaster to add to your growing list of disasters to worry about!! Sorry, this was NOT our idea and we sure don’t like having to add it to our own list of growing disasters, but here it is. This one is, sad to say, something to REALLY worry about. What can you do about it? Perhaps not much at the moment, but it is something you ought to know. Not knowing about it may be a good way to be surprised when the authorities find you to somehow come under the “authority” of this monstrosity.

“BLOCKING THE PROPERTY OF CERTAIN PERSONS ENGAGING IN SIGNIFICANT MALICIOUS CYBER-ENABLED ACTIVITIES”

1. The first provision asserts the power of the President of the United States, Barack Obama, to declare a national emergency because of the activities of persons located in whole or in substantial part outside of the U.S. to constitute a threat to the national security, foreign policy, and economy of the United States.

(Comment: That appears broad enough to include economic competitors to U.S. companies that are located in whole or in substantial part outside of the U.S. if, for example, they undercut the prices of American companies and, hence, “threaten” those companies by competing with them. An excellent excuse for special privileges for crony capitalists in addition to subjecting their competitors to the “blocking,” eg., freezing, of their properties in the United States)

(Comment #2: According to an analysis of this Executive Order, it allow the government to bypass due process and seize the assets (or at least to “block” them, whatever that means) of anybody suspected (suspicion does not require the filing of charges against or convicting anyone of anything) of hacking.

2. Under this Executive Order, President Obama orders that any person determined by the Secretary of the Treasury in any cyber-enabled activities that represent threats to those activities listed in point #1 above or an entity that has materially contributed to activities posing such threats may have their property and interests in property blocked pursuant to this order. The difference between civil forfeiture and “blocking” is not here defined.

The making of donations of specific types (as specified in section 203(b)(2) of IEEPA (50 U.S.C. 1702(b)(2)) are hereby prohibited by section 1 of this order. For example, if you donated money to an event at which Snowden gave a talk, you might come under this prohibition, in which case your assets might be “blocked” (frozen). The feds don’t even need to tell you whether prohibitions to that event are going to be treated as coming under this prohibition. Talk about having a chilling effect on freedom of speech!!

Other provisions include prohibition of “any transaction that evades or avoids, has the purpose of evading or avoiding, causes a violation of, or attempts to violate any of the prohibitions set forth in this order ...” and also prohibitions against “any conspiracy formed to violate any of the prohibitions set forth is this order...”

The executive order also “determines” that “there need be no prior notice of a listing or determination made pursuant to section 1 of this order.”

THE COMING OF MARTIAL LAW?

If you have been waiting for Executive Orders to invoke martial law, we may be seeing the first of the modern ones. “Hackers” are here being targeted as enemies of the state with the government setting them up to be deprived of their liberty and property without due process of law. And lest you think that although you use a computer, you aren’t a hacker, so you are safe from this, remember what happened to the Jews... “And when they came for me, there was nobody left who hadn’t already been taken away to help defend me.”

Don’t forget that we are still officially in a state of emergency as a result of executive orders from WWI, WWII, the Korean War, etc. etc.