June 2011 Blog with Durk and Sandy

A readers’ survey by Nature1 showed that one in five respondents already used some form of cognition-enhancing drug.
1. Maher, Nature 452:674-675 (2008).

The following quote helps explain why the United States federal government was designed as a government of limited powers (unlike a democracy, where the only limit is that a 50+% majority of the vote overrules the minority) and why there is NO mention of democracy in the Constitution:

[D]emocracies have ever been spectacles of turbulence and contention; have ever been found incompatible with personal security, or the rights of property; and have, in general, been as short in their lives as they have been violent in their deaths.
— James Madison,
Federalist No. 10, 1787

If, from the more wretched parts of the old world, we look at those which are in an advanced stage of improvement, we still find the greedy hand of government thrusting itself into every corner and crevice of industry, and grasping the spoil of the multitude. Invention is continually exercised, to furnish new pretenses for revenues and taxation. It watches prosperity as its prey and permits none to escape without tribute.
— Thomas Paine, Rights of Man, 1791

I believe that banking institutions are more dangerous to our liberties than standing armies. If the American people ever allow private banks to control the issue of their currency, first by inflation, then by deflation, the banks and corporations that will grow up around the banks will deprive the people of all property—until their children wake-up homeless on the continent their fathers conquered.
— Thomas Jefferson, 1802

Only those who will risk going too far can possibly find out how far one can go.
— T. S. Eliot

Natural disasters and man-made tragedies have always been a feature of life on Earth …
— Start of an editorial in the 14 Apr. 2011 Nature

(D&S Comment: Huh? These people seem to be getting farther and farther from reality.)
Niacin is even more effective than previously thought

Niacin Inhibits the Progression of Atherosclerosis
New Mechanisms Help Explain Its Protective Effects

Niacin is the most efficacious HDL cholesterol-elevating drug used in clinical practice. However, the mechanism by which niacin achieves that effect is still unknown. In a new paper,1 scientists report that in a mouse model of atherosclerosis, niacin inhibited the progression of the disease even though under the conditions of their experiment total cholesterol and HDL cholesterol plasma levels were unaffected.1

It has recently been discovered that niacin activates a receptor called GPR109A (its primary endogenous ligand—that is, its physiological activator—is not known, but the receptor is also activated by butyrate, formed in the colon by fermentation of fiber by gut microbes). When bone marrow was transplanted from mice lacking GPR109A into atherosclerosis-prone mice (whose own bone marrow had been destroyed by irradiation), the protective effect of niacin against atherosclerosis was eliminated,1 suggesting that immune system cells derived from the bone marrow are involved in the protective effects of niacin via GPR109A.

The researchers used male LDL-R deficient mice (mice deficient in the receptor for LDL) that were kept on a high fat diet (containing 1.5% cholesterol) to promote the development of atherosclerotic lesions. Of those mice, the ones that received 0.3% nicotinic acid (niacin) had a reduction of about 25% of atherosclerotic lesions in all regions of the aorta. However, in mice on the high fat diet lacking both the LDL receptor as well as GPR109A, the receptor for niacin, niacin provided no protection against atherosclerotic lesions—they were indistinguishable from the mice lacking both the LDL receptor and the GPR109A receptor and receiving no niacin. Hence, the niacin receptor was critically involved in the anti-atherosclerotic effect of niacin. As noted above, the beneficial effects of niacin in these genetically engineered mice were not accompanied by reduced LDL cholesterol levels, unlike in humans; in the two weeks of niacin treatment, only triglyceride levels showed a small reduction, by 11%–18.5%. “Thus GPR109A-dependent anti-atherosclerotic effects of nicotinic acid were not accompanied by any changes in cholesterol or HDL cholesterol plasma concentrations.”1

The researchers also discovered that macrophages, bone marrow derived immune cells that are important in the development of atherosclerotic plaques, express GPR109A. Macrophages that infiltrate atherosclerotic plaques carry fats such as oxidized LDL into the arterial intima where the macrophages then develop into foam cells. In this study, the authors found reduced recruitment of macrophages into atherosclerotic plaques by 75% under niacin treatment. Moreover, they found that niacin, via GPR109A, can change the differentiation state of macrophages, both in vitro and in vivo, inhibiting the development of the pro-inflammatory (M1) form of macrophages. Niacin also increased the expression of ABCG1, an important cholesterol transporter that promotes cellular cholesterol efflux, in macrophages from wild type but not GPR109A-deficient mice.

Interestingly, niacin also decreased the expression of MCP-1, an inflammatory mediator, in plaque macrophages exposed to IFN-gamma (interferon gamma).1 The authors cite other papers2,3 that recently showed that niacin suppressed expression of various inflammatory mediators, including MCP-1, in adipocytes (fat cells, which also express GPR109A) and increasing the expression of adiponectin, an important anti-inflammatory molecule released by fat cells.

Neutrophils are other bone-marrow derived cells that also promote the development of atherosclerotic plaques. The researchers® did not specifically examine the effects of neutrophils in this study, but note that they cannot exclude the possibility that neutrophils (which also express GPR109A) may have been involved in the anti-atherosclerotic effects of niacin seen in this study. They note that, importantly, niacin exerts a pro-apoptotic effect on neutrophils under in vitro conditions, as reported in a separate study by others.4 This could be of considerable importance in the many diseases in which prolonged activation of neutrophils delays the resolution of inflammation, resulting in chronic inflammatory diseases, such as COPD.

The authors conclude: “We conclude therefore that GPR109A mediates anti-inflammatory effects, which may be useful for treating atherosclerosis and other diseases.”

Another paper5 presents evidence that a variety of plant phenolic acids also suppress adipocyte (fat cell) lipolysis (release of fatty acids) via activation of the nicotinic acid receptor GPR109A. The authors explain that “both phenolic acids and nicotinic acid are small carboxylic acids with close structural similarity.” They also point out that “certain phenolic acids, such as benzoic acid, also induce a flushing response and prostaglandin D2 release in a manner similar to that of nicotinic acid treatment.” For example, they identified strong phenolic inhibitors of adipocyte lipolysis: as compared to nicotinic acid with an IC50 (μM) [amount needed to inhibit lipolysis by 50%] of 0.2μM, caffeic acid had an IC50 of 14 μM and gallic acid had an IC50 of 30 μM; both caffeic acid and gallic acid bound GPR109A but were far less potent binders than nicotinic acid.5

These new data add considerably to our reasons for taking niacin regularly. The two of us take 3 capsules of our niacin formulation capsules (200 mg of niacin per capsule) four times a day and have been doing so for over 25 years. Yes, we do experience flushing. Fortunately, neither of us find it troublesome. We know that the flushing is a major reason that many people won’t take more than a pellagra-preventing dose of niacin, which is not enough to provide the above effects. Taking niacin with food can help reduce the effect of flushing. However, we do not recommend time-release niacin, which has been found in a small percentage of people to have liver toxicity effects. Durk’s LDL and VLDL cholesterol and triglycerides run high (hypercholesterolemia and hyperlipidemia are familial traits) if he does not take niacin regularly.

Also, it is important to note that if you plan to take more than about 800 mg of niacin a day, you should have your liver tested periodically to ensure that your liver has no problem with high-dose niacin. The liver tests used to detect potential toxicity from high dose niacin are the same as those used to check for liver toxicity in people taking statins and, interestingly, the likelihood of experiencing liver toxicity is much higher in those taking statins as compared to niacin. Moreover, the muscle damage (rhabdomyolysis, a serious condition which can even be life-threatening) that occurs in a small fraction of those taking statins does not occur with niacin supplementation.

References

Lukasova et al. Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. J Clin Invest 121(3):1163-73 (2011).
Digby et al. Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin. Atherosclerosis 209(1):89-95 (2010).
Plaisance, Lukasova, et al. Niacin stimulates adiponectin secretion through the GPR109A receptor. Am J Physiol Endocrinol METAB. 296(3):E549-58 (2009).
Kostylina et al. Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A). Cell Death Differ 15(1):134-42 (2008).
Ren et al. Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA- G). J Lipid Res 50:908-14 (2009).

Selenium Protects Against 
Calcification in Blood Vessels by 
Preventing Vascular Smooth 
Muscle Cells From Acting Like Bone

A recent study¹ of rat vascular smooth muscle cells (VSMCs) in culture reports strong protective effects by selenium (in the form of sodium selenite) against calcification, frequently associated with atherosclerosis. Vascular calcification has been associated with oxidative stress, such as that of hydrogen peroxide, minimally modified oxidized LDL and different lipid peroxidation products.

Vascular calcification is an amazing (though damaging) process. VSMCs actually become induced (by oxidative stress, for example) to undergo differentiation to function like osteoblasts (bone-making cells). This osteoblastic differentiation is characterized by the expression of multiple bone-related molecules including ALP, Col I, and OC [osteocalcin] and upregulation of Runx2, a key transcription factor during osteoblastic differentiation of VSMCs.¹ The researchers explained that a growing body of evidence pointed to the importance of the activation of the ERK (extracellular signal- regulated kinase) pathway in the osteoblastic differentiation of VSMCs. They found that “sodium selenite alone at 0.1μM did not affect the level of ERK phosphorylation [activation](data not shown), but markedly inhibited H2O2 [hydrogen peroxide]-induced ERK activation [in the VSMCs].”

Moreover, the researchers showed that the intracellular ROS (reactive oxygen species) generation and MDA (malondialdehyde, a major lipid peroxidation product) content were significantly increased in the hydrogen peroxide treated VSMCs, while the content of protein thiols (that include molecules such as glutathione) and glutathione peroxidase activity were significantly decreased (indicating oxidative stress) after hydrogen peroxide treatment. Pretreatment with 0.1 μM sodium selenite for 24 hours significantly reversed the effects of hydrogen peroxide on intracellular ROS generation and the cellular contents of MDA and protein thiols.

The authors conclude: “These results indicate a potential preventive role for Se in vascular calcification, suggesting that vascular calcification may be another target of Se action in anti-atherosclerosis. However, our conclusion is just drawn from in vitro experiment. Due to the potential side effects of Se, the safety [of] using Se as [a] preventive drug for vascular calcification needs to be further addressed in animal experiments, especially in human experiments.”

We both take 400 μg of selenium per day in the form of sodium selenite. This is the upper limit of selenium doses considered safe by the Institute of Medicine of the National Academy of Sciences.

References

1. Liu et al. Selenium suppressed hydrogen peroxide-induced vascular smooth muscle cells calcification through inhibiting oxidative stress and ERK activation. J Cell Biochem 111:1556-64 (2010).

The 2010 Dietary Guidelines- The Latest Dietary Advice From the Government is No Help At All 

Good Advice: 
Fire the USDA and the HHS 

More Good Advice: 
Fire the FDA

The “new” Dietary Guidelines for Americans was released January 31, 2011 by the U.S. Dept. of Agriculture (USDA) and the U.S. Dept. of Health and Human Services (HHS) and—surprise, surprise—is not going to help anybody other than the bureaucrats whose salaries and plush benefits (extracted from taxpayers) depend upon their producing dietary advice and pretending it is valuable. Far better to fire these agencies, keep your money, and spend it on a more healthful diet, including expensive fruits and vegetables.

A commentary¹ by Dr. Roger Clemens, President-Elect of the Institute for Food Technologists (a professional scientific organization) questioned the feasibility of the guideline “tip” that you should make half the food on your plate fruits and vegetables. He said that “[a] 2006 report from the USDA’s Economic Research Service (based on 2002 data) indicates that an additional 8.9 million acres of cropland are necessary to support the guidelines’ vegetable intake recommendation and about 4.1 million more acres are needed to produce the advised fruit consumption. Independent modeling suggests that by 2015 an additional 10.3 million acres of cropland will be necessary to meet vegetable production needs and an additional 4.2 million acres for fruit production. Thus, total harvestable cropland would need to increase by about 3%,* or nearly 320 million acres, a level equivalent to 1997 acreage. Equally challenging is the production of fluid milk and milk products. The 2002 data suggest an increase of 107.7 billion pounds is needed [to meet the recommendation that Americans consume more low-fat dairy products], equivalent to a 66% increase in the number of dairy cows, feed grains, and grazing acreage.” All of this, of course, in the face of government subsidies for certain crops (soy, wheat, corn) which results in higher prices for these crops and much lower production of unsubsidized crops (farmers follow the money incentives, you know), as well as environmental organizations’ staunch opposition to opening up some of the federal government’s huge land estate (the feds control over 30% of the land area of the United States) to cattle grazing. Moreover, government mandates and subsidies have resulted in 40% of America’s corn crop being used to manufacture fuel ethanol, leaving less for human consumption and animal feed in the U.S. and export to a hungry world.

* It appears to us that this ought to be 30% rather than 3%.

In an article analyzing the 2010 Dietary Guidelines published in Food Technology,²the author asks: Does adherence to the Dietary Guidelines make us healthier? She notes that the cynical response is that no one adheres to the guidelines anyway so it doesn’t matter. More seriously, she adds, there have been NO intervention studies where people follow the Dietary Guidelines and are followed to observe long-term results. So much for a scientific basis for these “guidelines.” “Generally, adherence to the Dietary Guidelines is measured in epidemiologic studies by determining a healthy eating index (HEI), a measure of adherence to the diet recommendations of the Dietary Guidelines. McCullough et al (2000) found that the HEI was only weakly associated with risk of major chronic disease. Zemora et al (2010) determined the relationship between weight gain among black and white young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985–2005). The authors created a 100 point Diet Quality Index. They concluded that their findings do not support the hypothesis that a diet consistent with the 2005 Dietary Guidelines benefits long-term weight maintenance in young adults in America.” (see references in paper #1)

Another point made by Dr. Clemens¹ was that, since eggs are a primary source of choline (with approximately 125 mg of choline per whole fresh egg) and, since the Dietary Guidelines suggest that eggs be restricted to four per week (to minimize saturated fat and cholesterol), the required daily intake of choline (450–500 mg/day according to the Institute of Medicine) may not be achieved. Without adequate supplies of choline, memory, focus, and concentration will be subnormal, since choline is required for the brain to manufacture acetylcholine, a neurotransmitter vital for these functions. The supply of choline is particularly critical for older people, since the ability to transport choline across the blood-brain barrier into the brain decreases markedly with age.³ Of course, if you take a choline supplement (such as our sugar-free choline formulation), you needn’t be concerned about how much choline you get from your diet, but most people do not know about or take supplemental choline. The USDA or the HHS (parent organization of the FDA) would never recommend dietary supplements; in fact, the FDA will fine you, seize your “adulterated” (mislabeled) product, or throw you in jail and throw away the key if you dare to tell people on a label or in an ad for a choline-containing supplement or food (even eggs) that the choline in them might improve your memory, focus, and concentration.

References

1. Clemens. Dietary guidelines may produce unintended health consequences. Food Technol Feb 2011, pg. 22.
2. Slavin. Dissecting the Dietary Guidelines. Food Technol March 2011, pp. 40-7.
3. Cohen et al. Decreased brain choline uptake in older adults. JAMA 274(11):902-7 (1995).

Pain Relief Starts in the Brain

Blockade of TNF-alpha 
(Tumor Necrosis Factor-alpha) 
Inhibits the Brain’s Response to Pain 
Before It Reduces Joint Pain

Blockers of TNF-alpha have become very effective treatments for the serious pain and swelling of Rheumatoid arthritis and similar painful inflammatory disorders during the past ten years. The speed at which TNF-alpha blockade is able to reduce pain intrigued researchers, who have published a new paper showing (through the use of blood-oxygen level-dependent [BOLD] fMRI imaging) that changes in the brain precede the relief of pain in the periphery.¹

In fact, the researchers found that in as little as 24 hours after an infusion of a monoclonal antibody to TNF-alpha, nociceptive (pain) activity in areas of the brain that included the thalamus and somatosensoric cortex and also in the limbic system was blocked. This was before joint swelling and acute phase reactants in joints were affected by treatment. It worked the same in arthritic mice overexpressing human TNF-alpha that were treated with anti-TNF-alpha monoclonal antibodies. “Although it takes several weeks to observe a consistent and objective reduction of joint inflammation, many patients report on a rapid effect of TNF-alpha blockade on their subjective disease state.”¹

When TNF-alpha Is Enough and When It Is Too Much

One big problem, however, in inhibiting TNF-alpha too strongly is that it increases the risk of infection, since TNF-alpha is an important component of the immune system. As noted in another paper,² “[a]lthough therapeutic blockade of TNF-alpha worsens the prognosis in patients with abscesses and granulomatous infections, this strategy is highly beneficial in the case of chronic inflammatory conditions, including rheumatoid arthritis.” In other words, the ACUTE release of TNF-alpha in response to infection is generally appropriate, whereas CHRONIC elevated circulation levels of TNF-alpha often are not. For example, conditions that have been linked to increased chronic circulating levels of TNF-alpha include the neuroinflammation of postoperative cognitive decline,³endothelial dysfunction,⁴ bone loss in estrogen deficiency,⁵ and aging.⁶ Also, curiously, increased expression of TNF-alpha in response to LPS (a component of bacterial cell walls that activates the immune system) is associated with increased aggression and hostility in men, personality factors that have also been associated with an increased risk of cardiovascular disease.⁷ Persistence of inflammatory cytokines such as TNF-alpha can induce proatherogenic lipid patterns and insulin resistance.² In fact, those with chronic inflammatory conditions such as rheumatoid arthritis or lupus have a higher mortality due to cardiovascular disease than the general population.²

Natural Substances That Inhibit TNF-alpha

The herb Cat’s claw (Uncaria tomentosa) is a “remarkably potent inhibitor” of TNF-alpha production.⁸ It is a widely used herbal remedy for inflammatory conditions such as arthritis. In one study,⁸ researchers found that in cell culture (using mouse macrophages), LPS increased TNF-alpha in the culture medium from 3 to 97 ng/ml. Cat’s claw suppressed TNF-alpha production by 65–85%, but (the paper reports) “at concentrations considerably lower than its antioxidant activity: freeze-dried EC50 = 1.2 ng/ml, micropulverized EC50 = 28 ng/ml.”

Glycine is a nutrient amino acid that was shown to reduce TNF-alpha production in response to LPS in monocytes from healthy human donors.⁹ In the same study, glycine also increased the expression of IL-10, an important anti-inflammatory cytokine. The authors⁹ also reported that glycine has been shown to protect against endotoxin shock (in the early phase) by inhibiting TNF-alpha production.

Both quercetin and resveratrol have been reported to attenuate TNF-alpha-mediated inflammation and insulin resistance in human adipocytes (fat cells), with quercetin being equally or more effective than resveratrol.¹⁰

Other natural inhibitors of TNF-alpha release or production include xanthohumol (a component of hops),¹¹ fish oil (in a study of peripheral blood mononuclear cells of healthy men),¹² and the opioid antagonist naltrexone,¹³ to name a few.

References

1. Hess et al. Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci USA 108(9):3731-6 (2011).
2. Popa et al. The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 48:751-62 (2007).
3. Terrando et al. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci 107(47):20518-22 (2010).
4. Speciale et al. Cyanidin-3-O-glucoside protection against TNF-alpha-induced endothelial dysfunction: involvement of nuclear factor kappaB signaling. J Agric Food Chem 58:12048-54 (2010).
5. Cenci et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 106(10):1229-37 (2000).
6. de Gonzalo-Calvo et al. Differential inflammatory responses in aging and disease: TNF-alpha and IL-6 as possible biomarkers. Free Radic Biol Med 49:733-7 (2010).
7. Suarez et al. The relation of aggression, hostility, and anger to lipopolysaccharide-stimulated tumor necrosis factor (TNF)-alpha by blood monocytes from normal men. Brain Behav Immun 16:675-84 (2002).
8. Sandoval et al. Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 29(1):71-8 (2000).
9. Spittler et al. Immunomodulatory effects of glycine on LPS- treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression. FASEB J 13:563-71 (1999).
10. Chuang et al. Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-alpha-mediated inflammation and insulin resistance in primary human adipocytes. Am J Clin Nutr 92:1511-21 (2010).
11. Lupinacci et al. Xanthohumol from hop (Humulus lupulus L.) is an efficient inhibitor of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha release in LPS-stimulated RAW 264.7 mouse macrophages and U937 human monocytes. J Agric Food Chem 57:7274-81 (2009).
12. Grimble et al. The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. Am J Clin Nutr 76:454-9 (2002).
13. Greeneltch et al. The opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor necrosis factor-alpha production. Brain Behav Immun 18:476-84 (2004).

There May Be a Lot More 
Polyphenols in the Circulation 
Than Just Those Found in the Plasma

One of the current beliefs concerning dietary (or supplemental) polyphenols is that they are not well absorbed, as reflected in the very low concentrations found in blood plasma. In a new paper,¹ researchers propose that the proportion of total oxidant-scavenging capacity (TOSC) carried in the blood that is due to polyphenols cannot be adequately measured in just the plasma, but that the true TOSC can be derived only from including the red blood cells and plasma. They suggest that, “similar to microorganisms, blood cells (mainly red blood cells [RBC]) in the circulation might also avidly bind polyphenols to their surfaces resulting in enhanced TOSC.”¹ Thus, they propose that studies in which polyphenols were only determined by measuring their content in plasma have provided deceptively low levels because they did not include the polyphenols in whole blood, which includes red blood cells and platelets that also carry polyphenols.

The authors note that red blood cells contain antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase/reductase and NADH-metHgb reductase, as well as nonenzymatic antioxidants such as lipophilic (fat soluble) vitamin E, carotenoids, ubiquinone, melatonin, etc. and water-soluble vitamin C, glutathione, uric acid, ceruloplasmin, transferrin, haptoglobulin, etc. Plasma is rich in albumin and in low molecular weight antioxidants such as glutathione, ascorbate, alpha-tocopherol, uric acid, and bilirubin. Thus, the researchers say, “... it stands to reason that the TOSC of whole blood is the sum of the intracellular antioxidants present in RBC [red blood cells] and in other blood cells, the antioxidants bound to their surfaces and those found in plasma.”¹

The authors, on the basis of the studies described in their paper,¹ argue that “since erythrocytes [red blood cells] can form stable complexes with polyphenols, they acquire the ability to act in concert with LMWA [low molecular weight antioxidants] and with albumin to enhance TOSC.” “The minute quantities of polyphenols detected in plasma do not reflect the true amount of polyphenols which gain access to the circulation, since these agents might also be complexed with circulating erythrocytes [red blood cells], removed and therefore not accounted for if TOSC is tested exclusively in plasma.” They further propose, on the basis of their findings concerning the binding of polyphenols to red blood cells that “human erythrocytes play a pivotal role in the distribution and bioavailability of circulating polyphenols and in protection against cell damage induced by ROS [reactive oxygen species].”

The analysis¹ was done using freshly collected non-fasting human blood from 11 healthy volunteers. The researchers used a “cocktail” of substances to generate at room temperature a flux of hydrogen peroxide and of cobalt-catalyzed hydroxyl radicals, which were detected by luminol-dependent chemiluminescence assay. Using the luminescence assay, Figure 3a in the paper “shows that incubation of whole blood with eight antioxidant agents followed by removal of unbound materials by washing resulted in a decrease in luminescence. It indicated that RBC [red blood cells] in whole blood could bind polyphenols and that gallic acid, curcumin and resveratrol were the most potent polyphenols [of those tested by the authors] attached.” In a separate analysis using a different test (fluorescence confocal microscopy), polyphenols (morin, resveratrol, curcumin, and tannic acid) were exposed to washed erythrocytes. The most potent quenchers of luminescence were (in descending order) wine/tannic acid, curcumin, resveratrol, and morin. In addition, using a different method (differential pulse voltammetry), the authors confirmed that polyphenols remained attached to the washed erythrocyte surfaces. They hypothesize, therefore, that “erythrocytes and possibly other blood cells in the circulation might always be coated, in a cumulative manner, with polyphenols, which gain access to the circulation from nutrients.”¹

These are very exciting findings that we hope will be followed up by further research. As the authors note, “the nature of the binding of polyphenols to erythrocyte surfaces is still not fully clear ...” but suggest that they might do so via hydroxyl groups, hydrophobic interactions, hydrogen bonding, or other mechanisms. The binding of polyphenols to red blood cells and possibly other blood cells could help explain the important protective effects of polyphenols (in cardiovascular disease, cancers, neurodegenerative diseases, and others) despite the very low concentrations previously reported in plasma.

The authors also promise more to be published on this line of research. They say that “[i]n recent observations (to be published) RBC were also shown to synergize strongly with washed platelets, lymphocytes, salivary antioxidants and with plasma to enhance TOSC.” They even propose that following destruction of red blood cells in the spleen, “higher levels of polyphenols might be accumulated in this organ” and say further that “[s]tudies along this line are now in progress.” Bravo!

Reference

1. Koren, Kohen, Ginsburg. Polyphenols enhance total oxidant-scavenging capacities of human blood by binding to red blood cells. Exp Biol Med 235:689-99 (2010).