A loser is someone who won’t take “yes” for an answer.— Sandy Shaw
Narcissurfing — Googling yourself to see where and how many times your name comes up.— from “The Buzzword Dictionary”
Evils which are patiently endured when they seem inevitable become intolerable when once the idea of escape from them is suggested.— Alexis de Tocqueville 1856
I consider the foundation of the Constitution as laid on this ground that ‘all powers not delegated to the United States, by the Constitution, nor prohibited by it to the states, are reserved to the states or to the people.’ To take a single step beyond the boundaries thus specially drawn around the powers of Congress, is to take possession of a boundless field of power, not longer susceptible of any definition.— Thomas Jefferson, Opinion on the Constitutionality of a National Bank, 1791
Schroedinger’s cat walks into a bar ... and doesn’t.— US comedian Brian Malow
(as reported in the 30 Sept. 2010 Nature).
Inflammatory processes are involved importantly in the development and progression of cancer, cardiovascular disease, and aging, as well as age-associated diseases such as diabetes and Parkinson’s disease. Inflammation has also been linked to many forms of psychological stress, as well, such as depression. Here, an interesting new study1reports that, in 124 young, healthy human volunteers, exposure to laboratory-based social stressors (the Trier Social Stress Test, TSST), especially those involving judgment by others and possible social rejection, elicited significant increases in two markers of proinflammatory activity, a soluble receptor for tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).
The stress test involved preparing and delivering an impromptu speech and performing difficult mental arithmetic in front of a nonresponsive, socially rejecting panel of raters. (Fun, huh?) Later, 31 of these participants were fMRI scanned while playing a computerized ball-tossing game in which two other supposed game participants booted them from the game, thus socially rejecting them. The researchers compared the inflammation results to that of the TSST.
Similar inflammatory increases occurred after the stressors without differing on the basis of gender, ethnicity, or body mass index. Brain regions previously implicated in processing rejection-related distress and negative affect, including the dorsal anterior cingulate cortex and the anterior insula, were found to be activated. The greater the inflammatory responses, the greater the activity in these brain regions. Interestingly, the authors report, “the relations between neural activity and inflammatory responding were found despite the fact that the neuroimaging session and social stressor session took place several weeks apart. This result suggests that these neural patterns of responding represent at least a moderately stable trait that, in turn is involved in potentiated inflammatory responses to social stress.”
What these results suggest to us, in addition, is that modulation of inflammatory responses by omega-3 fatty acid supplementation may reduce the inflammatory responses and accompanying social distress resulting from rejection. Next time you have to give an impromptu speech and do difficult mental arithmetic before a nasty audience, give it a try. We take 2 capsules 4 times a day of our omega-3 fish oil formulation to get a total of 1.6 g. of DHA and 2.88 g. of EPA daily. You won’t have to worry about embarrassing EPA and DHA fishy-smelling burps in front of your highly critical audience, either, because our formulation is specially purified and deodorized.
You may not want to increase the lifespan of pesky banana fruitflies making nuisances of themselves around your fruit, but as a model organism for lifespan studies, they work well. A 1989 paper1 reports on a study of sodium selenite supplementation in banana fruitflies (added at nine concentrations: 1, 5, 10, 25, 50 100, 500, 1000, and 2500 uM) increased mean and maximum lifespans and increased catalase and peroxidase activity. “The best suited concentration of SS [sodium selenite], 5 uM, increased the median life span of males by 11.63% and that of females by 7.69%. The maximum life span was increased by 5.06 and 3.29% in males and females, respectively.”
In the control flies, reared on standard corn meal agar medium without sodium selenite supplementation, males exhibited a decline in catalase activity of 59.4% up to 13 days followed by an increase of 55.8% up to 37 days; in females, catalase activity declined during the first 25 days by 60% followed by a 38.64% increase at the 37 day stage. Both males and females showed a statistically significant increase in the baseline activity of catalase as a result of sodium selenite supplementation followed by similar age-related changes as shown by the control flies. The peroxidase changes were more complex; the authors infer from these changes that catalase and peroxidase are inversely related and that the changes associated with reproduction may be an adaptive response to higher levels of hydrogen peroxide production.
We each take 400 ug. (2 capsules) of our sodium selenite per day.
Protection by Trehalose Against Mutant Protein
Causing a Neurodegenerative Disease
As we have written before (see “The Origami of Aging” in the September 2008 issue), trehalose is a natural disaccharide (sugar) found in many plants, bacteria, yeast, fungi (mushrooms can contain up to 10-25% trehalose by dry weight*), insects, and invertebrates but not in mammals1 that acts as an osmolyte, a type of chaperone that helps proteins to fold properly. “Trehalose has also been shown to inhibit the aggregation of disease-related proteins, including polyglutamine- expanded huntingtin in Huntington disease, beta-amyloid in Alzheimer disease, and protease-resistant prion protein in prion disease.” 1 Trehalose has been reported to improve motor dysfunction in a mouse model of Huntington disease. 1b
* Higashiyama. Novel functions and applications of trehalose. Pure Appl Chem 74(7):1263-1269 (2002).
Osmolytes such as trehalose can help protect against the improper protein folding2,3(and accompanying protein dysfunction) that occurs with increasing frequency with aging. We report here further evidence of the protective effects of trehalose in another neurodegenerative disease, spinocerebellar ataxia type 14 (SCA14), which is associated with genetic mutations such as CAG trinucleotide repeats (the type of mutation found in Huntington disease) in the gene for protein kinase Cgamma.
Though SCA14 is an uncommon disorder, the importance of preventing improper protein folding applies broadly to many different proteins. Hence, we were delighted to see this new research with trehalose. As the authors1 state: “we believe that drugs that inhibit the aggregation of mutant gammaPKC might be useful to treat SCA14 and related neurodegenerative diseases.” (Trehalose is a natural product, however, not a drug. It is the FDA that has decided that anything that can be used to treat a disease is a drug even if they are natural products available as dietary supplements or as components of foods. As the fact that dietary supplements or foods can be used to treat some diseases is “forbidden knowledge,” no one selling dietary supplements or foods can communicate this information to the public without risking a big fine or even prison. (Notice how this is analogous to earlier attempts by organized religion to monopolize the content of their holy books by prohibiting their being published in anything but Latin, which could only be understood by priests certified by the Church. This stuff doesn’t go away, folks, it just gets continually resurrected to be administered by bureaucracies with new names and updated punishments.)
Anyway, getting back to trehalose ... The authors show that trehalose reduced the aggregation of the mutant gammaPKC, “thereby inhibiting the apoptotic cell death in SH-SY5Y cells and primary cultured Purkinje cells.” Trehalose was found to act by directly stabilizing the conformation of mutant gammaPKC without affecting protein turnover.
The authors conclude that “[t]rehalose is widely used in foods as a sweetener and in cosmetics as a humectant; thus its safety has already been established. We expect that trehalose has the potential to become a useful drug for treatment of neurodegenerative diseases, including SCA14.”
We have included trehalose in our osmolyte formulation to help proteins fold properly. Each tablespoon (1 serving) of this formulation contains 1000 mg of trehalose plus 500 mg to 1500 mg of each of 7 other osmolytes (betaine, creatine monohydrate, glycine, inositol, L-proline, taurine, and beta alanine).
Although pu-erh tea is made from Camillia sinensis, the same plant whose leaves are used to derive white, green, oolong, and black teas, it is produced by different, more complex and often lengthy fermentation and heat treatment processes resulting in a tea with a different flavor and some differences in component ingredients as compared to the other teas. Pu-erh tea has been shown to have anti-obesity, hypolipidemic, and hypocholesterolemic effects. 1 Recently, a paper2 has identified an ingredient, theabrownin, that may be the main bioactive component in pu-erh tea. This rust-brown colored pigment is also found in black tea but at lower concentrations (4% to 9% in black tea as compared to 10% to 14% in pu-erh tea). 2
Recent studies performed by and cited2 by the authors of paper #2 have shown that theabrownin (TB) fractionated from pu-erh tea has a significant blood lipid-lowering effect, reducing serum triglyceride, total cholesterol and low density lipoprotein (LDL), while increasing HDL in rats fed a high fat diet (though not in those on a normal diet). The authors hypothesized that these effects were a result of alterations by TB in key enzymes involved in lipid metabolism and/or on cholesterol breakdown and excretion. (The authors explain that the high fat test diet contained added fat and cholesterol and also had small amounts of bile salts added to “help” the rats to absorb the cholesterol contained in the diets because rats do not absorb cholesterol very well, not nearly as well as rabbits. Next time, they say, they will use rabbits! Perhaps they did not have enough money to do so this time.)
The results showed that the rats fed TB-supplemented high fat diet were prevented from developing the diet-induced increases in serum total cholesterol, triglycerides, and LDL cholesterol as compared to the rats fed the high fat diet without TB. The TB-supplemented high fat diet fed rats also maintained their HDL at the same level as the control rats fed the regular (no added fat and cholesterol and no added bile salts) diet, and had HDL more than twice that of the decreased levels in the unsupplemented rats fed the high fat diet. TB supplementation caused an increase in the activity of hepatic lipase and hormone- sensitive triglyceride lipase, which the authors propose is important in the cholesterol reducing effects of the TB.
Theabrownin Dramatically Increased Excretion of Cholesterol
The feces of the TB-supplemented high fat diet fed rats had greatly increased levels of cholesterol and bile acids (21.11- and 4.08-fold greater, respectively) as compared to the unsupplemented high fat diet fed rats, thus demonstrating a huge increase by TB in the excretion of cholesterol. Moreover, TB “alleviated and slowed” the liver pathology (fatty liver) that ordinarily occurs in rats fed a high fat diet and indeed was induced in the rats on the high fat diet without TB.
Though we subscribe to many scientific journals, including some (such as Lipids and J Lipid Res) that are specifically devoted to research on lipids, we do not often find research on pu-erh tea (most of which is done in China and published in Chinese). We hope that there will be more such research; we are particularly interested in its lipogenesis (fat synthesis) inhibiting effects, 3,4 which is why we include pu-erh tea in our special selection of teas formulation for helping reach and maintain a healthy body fat content.
According to a recent paper, 1 twenty million adults in the U.S. 20 years or older have an increased serum creatinine level (creatinine is cleared by the kidneys) and the incidence increases with age. The paper further notes that more than 20% of those age 65 years or older have decreased kidney function, even when corrected for obvious causes of kidney dysfunction such as hypertension and diabetes. Moreover, there is a strong association between age-associated chronic kidney disease and cardiovascular disease, since inflammatory mechanisms are involved in both. 1 Surprisingly, “results from a longitudinal study of normal [not diabetic] aging adults in Italy showed that the most significant correlation with mortality was the level of renal [kidney]
Hence, if you have reached 65 years of age, having successfully avoided being done in prematurely by cardiovascular disease and cancer, declining kidney function is a major factor to consider in all-cause mortality and you should have your kidney functions tested regularly as part of your health assessment. Declining kidney function in aging is associated with increased levels of the cytokine IL-6, C-Reactive Protein, and other markers of inflammation and oxidative stress. Importantly, increasing quantities of serum AGEs accumulate in the kidneys and impair their function. In a recent paper, 1the authors refer to studies showing that reducing AGEs in the diet of both animals and humans (by, for example, cooking foods at a lower temperature) is one effective way of reducing serum AGEs and protecting kidney function. Other ways (not discussed in this paper) include dietary supplements of nutrients that decrease the formation of AGEs or interfere with the pathways of damage initiated by AGEs.
Serum Advanced Glycation End Products (AGEs) Associated with Kidney Function Decline
The kidneys are the major way the body has for excreting AGEs to maintain the body load of AGEs at nontoxic levels. 1 It has been shown that during aging and in diabetes, the glomerular basement membrane of the kidneys are thickened, leading to less efficient kidney filtration. 2 (Interestingly, thickening of the basement membrane of other organs, such as the testes, also occurs with aging.) This thickening has been linked to glycosylation (an early part of the process that produces AGEs) of the collagen type IV that makes up more than 80% of the glomerular basement membrane material. 2 AGE inhibitors have been reported to provide significant protection against cardiovascular disease as well as age-associated decline in kidney function.
Reducing Accumulation of AGEs in Kidneys with L-Arginine
The amino acid L-arginine has been shown to be a reducer of cross-linking in aging collage type IV and is strongly associated with a reduction of collagen accumulation of N-epsilon-(carboxymethyl)lysine (an AGE) in aging mice and in diabetic mice. 2
Another paper attests to the kidney protective effects of L-arginine. 3 12-13 month old rats treated for 8 months with L-arginine had their glomerular filtration rate increased by 50% as compared with untreated controls. Another study4 reported that 12 week old hyperlipidemic, hyperglycemic Golden Syrian hamsters had enhanced accumulation of fluorescent AGE-proteins in the vascular mesenteric bed and in the lens, which was decreased significantly by L-arginine treatment.
Reducing the Accumulation of AGEs with Rutin, Alpha-lipoic acid, Carnosine, Benfotiamine, Histidine, and Pyridoxine hydrochloride (Vitamin B6)
As we have written earlier (see “Reducing Glycation Reactions for Better Health and Longer Life” in the February 2008 issue of Life Enhancement), certain nutrients, such as those listed above, have been found to be remarkably effective in preventing the formation of damaging AGEs. We incorporated the listed nutrients in our antiAGE formulation that includes rutin, alpha-lipoic acid, carnosine, benfotiamine, histidine, and pyridoxine hydrochloride (vitamin B6) and we each take 6 capsules a day. As an AGE-reduced diet in mice has been found to induce some of the same genetic changes as CR (calorie restricted) fed mice, 1 we hope that taking AGE-reducing nutrients (as well as reducing cooking temperature as often as possible to decrease AGE formation in food) may provide us with similar benefits. In addition, to the antiAGE formulation, we also take two servings a day of our L-Arginine (6 grams per serving) plus cofactors formulation.
1 Vlassara et al. Identifying advanced glycation end products as a major source of oxidants in aging: implications for the management and/or prevention of reduced renal function in elderly persons. Semin Nephrol 29(6):594-603 (2009).
1b Pizzarelli et al. Predictivity of survival according to different equations for estimating renal function in community-dwelling elderly subjects. Nephro. Dial Transplant 24:1197- 1205 (2009).
2 Radner et al. L-arginine reduces kidney collagen accumulation and N-epsilon-(carboxymethyl)lysine in the aging NMRI-mouse. J Gerontology: Med Sci 49(2):M44- M46 (1994).
3 Reckelhoff et al. Long-term dietary supplementation with L-arginine prevents age-related reduction in renal function. Am J Physiol 272(6 pt 2):R1768-74 (1997).
4 Georgescu and Popov. Age-dependent accumulation of advanced glycation endproducts is accelerated in combined hyuperlipidemia and hyperglycemia, a process attenuated by L-arginine. J AmerAging Assoc 23:33-40 (2000).
Newly Discovered Receptor for Omega-3 Fatty Acids Mediates Potent
Anti-Inflammatory and Insulin- Sensitizing Effects
The Sept. 3, 2010 Cell1 contained a very exciting paper that reports the discovery that a receptor (GPR120, formerly an orphan receptor), when stimulated by omega-3 fatty acids (DHA and EPA) and palmitoleic acid (found in especially large amounts in macadamia nut oil), causes broad anti-inflammatory effects in immune system cells (RAW 264.7 monocytes and primary intraperitoneal macrophages). Chronic inflammatory effects due to infiltrating macrophages in adipose tissue is a major cause of insulin resistance. 2 When obese mice were fed a high fat diet with omega-3 fatty acids, the fatty acid treatment inhibited inflammation and enhanced systemic insulin sensitivity. But the same omega-3 fatty acid treatment had no such effect in mice whose GPR120 receptor had been knocked out, demonstrating that the effect is mediated by the GPR120 receptor.
The researchers found that stimulation of GPR120 inhibits both TLR4 (toll-like receptor 4)- and TNF-alpha (tumor necrosis factor-alpha) mediated inflammatory responses, thus showing that omega-3 fatty acids can modulate these powerful immune system inflammatory signaling molecules. Also, importantly, GPR120 stimulation by omega-3 fatty acids in wild type mice resulted in a decrease in macrophage proinflammatory genes (M1 type) and an increase in macrophage anti-inflammatory (M2 type) gene expression in adipose tissue. Chronic inflammation in adipose tissue is associated with many complications resulting from diabetes and obesity, such as cardiovascular disease, as well as being a causative factor in aging. 3
Reversal of Fatty Liver by Omega-3 Fatty Acids
The authors also did an in detail lipidomic analysis of fatty acids in the liver and found that the high fat diet-induced increases in triglycerides, diacyglycerol, total saturated fatty acids, and omega-6 fatty acids in the liver were all ameliorated by omega-3 fatty acid treatment and suggest that, “these results are consistent with the view that the reversal of steatosis/non- alcoholic fatty liver disease (NAFLD) by w-3 FA treatment is mediated, in large part, by GPR120 and that the GPR120 KO [knockout] mice are predisposed toward NAFLD even in the context of w-3 FA supplementation.”
We each take 2 capsules four times a day of our omega-3 EPA and DHA supplement. (See "Protect and Enhance Hearts and Minds” in the September 2010 issue of Life Enhancement).
Main Meal Roasted Chili-Citrus Chicken Thighs with Olives and Leeks
(adapted from a recipe appearing in Bon Appetit magazine)
8 large skinless chicken thighs with bone in. (Sandy used boneless skinless thighs. Skinless drumsticks should work, too.)
2 Tbsp. or more if desired, lime juice, divided
1/3 cup fresh orange juice (about the amount in 2 large navel oranges)
3 Tbsp. chili powder
1 Tbsp. paprika
1 Tbsp. smoked paprika
2 teaspoons finely grated orange peel (about the amount from 2 large navel oranges)
1 tsp. ground cumin
1/2 tsp. dried oregano
1/2 tsp. salt
2 Tbsp. extra-virgin olive oil
1 cup low fat chicken broth
2 Tbsp. coarsely chopped fresh cilantro, divided
1 Tbsp coarsely chopped fresh parsley
50 olives (for pretty appearance, get olives in varied colors and sizes)
3 leeks, about 18” long (recipe calls for potatoes, but if you want to avoid high glycemic index food, don’t use regular potatoes; sweet potatoes would be fine. We used leeks as our local supermarket — remember, we live in the boonies — doesn’t usually carry sweet potatoes.
Preheat oven to 400 degrees F.
Place chicken thighs and/or drumsticks on large heavy-duty rimmed baking sheet. Sprinkle chicken with salt and drizzle with 1 Tbsp. lime juice. Set aside. Whisk 1 Tbsp. lime juice, orange juice, chili powder, the two types of paprikas, grated orange peel, ground cumin, dried oregano, and 1/2 tsp. salt in small bowl. Rub the chili mixture all over the chicken. Trim off tough outer covering from leeks and cut trimmed leeks into 3 inch pieces. Nestle pieces of leek around chicken in baking dish. Drizzle olive oil over the chicken and leeks. Put baking sheet with chicken and leeks into oven and bake for 20 minutes. Increase oven temperature to 425 degrees F. Turn chicken and leeks, spoon juices over, and bake for another 10 minutes. Check to see that chicken is fully cooked. (Recipe called for another 10 minutes of baking, but Sandy found that the boneless chicken she used was fully cooked at this point.) Transfer cooked chicken and leeks to serving plate. Then put baking sheet over two stovetop burners. Add the chicken broth, chopped cilantro, and chopped parsley, along with the olives to the cooking juices in the baking sheet. Boil sauce until reduced to 1 cup (as called for in the recipe) or retain more liquid if desired (we did). You can either pour sauce over the chicken and leeks in the serving platter or, as we did it (easier to get at the sauce), spoon out the chicken and leeks into serving bowls and then pour the desired amount of sauce over each serving.
This recipe is mind-bogglingly good and good for you! Who says that healthy food has to taste like monkey chow?
SNACK: Cheese Puffs With (or Without) Heat
Snacking can be a problem if you want to avoid high glycemic index and high calorie food and yet enjoy tasty baked snacks between meals. This recipe, with low glycemic index and high fiber Glycemic Control™ barley flour works to make a great tasting, fun snack. NOTE: Though the recipe calls for butter, we use a butter-olive oil blend that works well in this recipe. Also remember that the 4 tablespoons of butter (or butter-olive oil blend) is contained in the approximately 50 cheese puffs, so the amount of butter in each puff is very small (slightly more than 1 gram per puff).
We got this recipe (but substituted our Glycemic Control barley flour for the flour they called for) from King Arthur Flour (The Baker’s Catalogue, kingarthurflour.com/shop). The ingredients marked by an asterisk are available from that catalogue.
1 cup (8 ounces) water
4 Tbsp. (2 ounces) butter or butter-olive oil blend
1/4 tsp. salt 1/4 tsp. dry mustard powder
1/4 tsp. cayenne pepper (or use just a pinch if you don’t like the heat)
1/2 tsp. black pepper
2 tsp. Pizza Seasoning*
2 tsp. Pizza Dough Flavor* (we didn’t use this ingredient)
1 cup Glycemic Control barley flour
3 large eggs plus 1 large egg white
1/2 cup (2 ounces) sharp cheddar cheese powder*
Preheat oven to 400 degrees F. Grease two large baking sheets, or line with parchment.
Put the water and butter in a saucepan and heat to boiling. Add the flour and seasonings all at once and stir until a ball of dough forms. Remove from the heat and scrape the dough into a bowl. Beat for 2 minutes, to cool slightly.
Add the eggs one at a time, beating each egg in completely before adding the next egg. Then beat in the egg white, then the cheese powder.
Using a teaspoon scoop (or two spoons), deposit the dough in level scoops (1” balls) onto the baking sheets, leaving about 1 1/2” between balls to allow for expansion.
Bake the puffs until golden brown, about 15 minutes. Turn the oven off, crack the door open, and leave puffs in the cooling oven for about 5 minutes. Remove from the oven and serve warm or at room temperature.
Said to make about 60 puffs; we got 50. This is a really delightful snack that goes great with soups and salads or all by itself! Contains lots of fiber.
NOTE: These cheese puffs did not puff up much, but came out rather flat like pancakes. I don’t know why the recipe didn’t include baking soda or baking powder, but will try using a little of that next time. — Sandy