End-stage renal disease is an organ harvester of no good end …

Purple Corn Combats
the Renal Reaper

In a new study, researchers noted that diabetic nephropathy is one of the major
diabetic complications and the leading cause of end-stage renal diseases.

By Will Block

The afternoon passed more slowly than a walnut-sized kidney stone.
—Tom Robbins, Villa Incognito

As of now while we read this, we are untouched by death—at least directly. Yet all of our lives, we have been surrounded by bereavement, so we know the grim reaper by his deeds … without ever having met him. In order to oppose the swing of his scythe and the consequential death knell, the adoption of a healthy lifestyle and the dietary inclusion of powerful and proven supplements is advocated. Because each of us may be predisposed to one or more illnesses, it is useful to consider what others have died from and how some supplements have been shown to reduce their risk of, shall be say, expiration. The leading causes of death follows (along with some of the supplements that have been found to help reduce the risks):*

  1. Heart disease—your avoidance chances are good, especially given the use of niacin and fish oil, among other supplements.

  2. Cancer—there are few cancers that can’t be dealt with (or your chances greatly improved) if identified early in time, especially given the use of selenium, and vitamin D3, among other supplements.

  3. Chronic lower respiratory diseases—choline, vitamin C, vitamin D3, the flavonoid quercetin, green tea extract (90% polyphenols, 50% of which is EGCG), N-acetylcysteine, resveratrol, boswellia, turmeric, Ginkgo biloba, isoleucine, theanine, and other nutrients have shown favorable responses.

  4. Stroke (cerebrovascular diseases)—fish oil, resveratrol, potassium bicarbonate, and other nutrients are warranted.

  5. Accidents (unintentional injuries) … these are far more likely to occur when we are less aware and weakened—memory supplements such as choline and phenylalanine; strength supplements such as arginine and citrulline; joint supplements such as glucosamine, chondroitin, turmeric, boswellia, and others can be quite beneficial.

  6. Alzheimer’s disease—galantamine, choline, vitamin B5, fish oil, and other nutrients have been shown be helpful.

  7. Diabetes—water-soluble procyanidins (type A) and MHCP from cinnamon, along with α-lipoic acid, chromium, resveratrol, epigallocatechin gallate (EGCG) from green tea, mulberry-leaf extract, the B-vitamin biotin, berberine, mulberry, and other nutrients can be valuable.

  8. Influenza and pneumonia—isoleucine, theanine, berberine, vitamin D, resveratrol, and other supplements have been found to support.

  9. Nephritis, nephrotic syndrome, and nephrosis—arginine, anti-AGE supplements, and now purple corn color (extract) are valuable (see below).

  10. Intentional self-harm, aka, suicide—natural antidepressives such as tryptophan and 5-HTP may be helpful.


* Centers for Disease Control and Prevention. Leading Causes of Death. Available at: www.cdc.gov/nchs/fastats/lcod.htm Updated: January 27, 2012. Accessed: July 25, 2012.


Aside from accidents and suicide, perhaps the least defensible of the entire list to date (data from 2009) are the kidney diseases, including nephritis, nephrotic syndrome, and nephrosis.§ You may survive heart disease, cancer, respiratory disease, stroke, even Alzheimer’s disease, but sooner or later end-stage kidney disease will take you out. That’s because when your basement membrane dysfunctions with age, you become unable to remove toxins from the body. Then, we literally poison ourselves and finally get to meet the grim reaper! But this needn’t happen.


† The inflammation of the nephrons (the basic structural and functional unit of the kidney) in the kidneys.

‡ A nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine.

§ A group of symptoms that include protein in the urine, low blood protein levels, high cholesterol levels, high triglyceride levels, and swelling.


Diabetic Nephropathy: A Major Cause of Renal Failure

Figure 1. A kidney glomerulus—where the vital process of glomerular filtration is performed.

(click on thumbnail
for full sized image)
In a new study, researchers noted that diabetic nephropathy is one of the major diabetic complications and the leading cause of end-stage renal diseases.1 In its early stages, renal injury and macrophage accumulation take place in the glomerular blood vessels which are adjacent to renal mesangial cells—specialized smooth muscle cells that function to regulate blood flow through the capillaries—expressing pro-inflammatory mediators. The kidney possess a million or so glomeruli, microscopic “knots” of thin-walled capillaries through which waste molecules pass out of the blood and into the urine. This vital process is called glomerular filtration (see Fig. 1).

Purple corn has been used as a daily food because it is rich in anthocyanins—naturally colored molecules that give certain fruits and vegetables their red, blue, and purple colors—that are known to exert disease-preventive activities as a functional food. The design of the study was to elucidate whether anthocyanin-rich purple corn ­extract could suppress monocyte activation and macrophage infiltration, thereby allaying damage to the kidneys.

The study consisted of two rather complicated parts: In the in vitro study, human endothelial cells and THP-1 monocytes (a leukemia cell line) were cultured in conditioned media of human mesangial cells along with glucose. Purple corn extract decreased the glucose conditioned media-induced expression of endothelial vascular cell adhesion molecule-1, E-selectin, and monocyte integrins of β1 and β2 through blocking the mesangial Tyk2 pathway, which encodes for tyrosine kinase, an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an “on” or “off” switch in many cellular functions.

In the in vivo animal study, obesity/diabetes model mice were treated with 10 mg/kg purple corn extract daily for 8 weeks (the equivalent of about 150 mg/day for a 187 lb human). Purple corn extract lessened the CXCR2 induction (CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family) and the activation of Tyk2 and STAT1/3** in obesity/diabetes model mice. Periodic acid-Schiff staining showed that purple corn extract reduced mesangial expansion-elicited renal injury in diabetic kidneys.


** STAT1 is a member of the Signal Transducers and Activators of Transcription family of transcription factors, and is involved in upregulating genes due to a signal by either type I, type II or type III interferons. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis.


In glomeruli, purple corn extract reduced the induction of intracellular cell adhesion molecule-1 and cluster of differentiation molecule 11b (CD11b). It also diminished monocyte chemo-attractant protein-1 (MCP-1) expression and MIP-2 (MIP-2-gamma is expressed constitutively in most normal tissues with the greatest expression in the kidney) transcription in diabetic kidney, inhibiting the induction of the macrophage markers of the antibodies CD68 and F4/80.

Altogether, these results demonstrate that purple corn extract antagonized the infiltration and accumulation of macrophages in diabetic kidneys through disturbing mesangial IL-8-Tyk-STAT signaling pathway. Therefore, purple corn extract may be a potential renoprotective agent treating diabetes associated glomerulosclerosis, the hardening of the glomerulus in the kidney. Glomerulo­sclerosis is a general term to describe scarring of the kidneys’ tiny blood vessels, the glomeruli, the functional units in the kidney that filter urine from the blood.

An Array of Other Benefits

Purple corn is rich in the anthocyanin C3G (cyanidin-3-glucoside), which is used extensively in Japan as a food color in confections and soft drinks. Beyond its esthetics, purple corn color has been found in scientific studies to have beneficial properties. Among these is the ability to increase an important antiatherosclerotic molecule, adiponectin, which is reduced in the bloodstream of obese humans and mice and in insulin-resistant states2 (in fact, when adiponectin was administered intravenously to mice fed high-fat/sucrose diets, weight gain was significantly inhibited). Another beneficial property is its potent antioxidant activity.3-5

An Antiobesity Effect

And finally, purple corn extract has been shown to have the ability to prevent obesity in mice on a high-fat diet.6 In a 12-week study of the effects of C3G-rich purple corn extract on obesity and hyperglycemia in mice, mice were fed a regular lab diet; or the regular diet plus purple corn extract; or the regular diet plus high fat; or the regular diet plus high fat plus purple corn extract. The purple corn extract supplement was added to diets at a C3G concentration of 2 g/kg of diet (that’s pretty high, although even at that height, toxicity is of low concern).

The researchers found that the mRNA of fatty acid synthase (the final enzyme in the synthesis of fat) was 81% lower in the high-fat-plus-purple-corn-extract group (as compared to controls) and 57% lower than the high-fat group. While the high-fat diet increased the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) to 253.5 ± 41.9, as compared to 100 ± 5 on just the regular diet,, the addition of purple corn extract to the high-fat diet group resulted in a TNF-alpha level of 109.3 ± 14.0, which was not significantly different from the regular diet. The problem with high levels of TNF-alpha is that it is strikingly increased in obesity and contributes to the increased risk of many diseases. This includes atherosclerosis, an obesity-prone disease.

Effects of High-Fat Diet Blocked by Purple Corn Extract

The study’s results on body weight showed that the control and high-fat-plus-purple-corn-extract groups did not differ throughout the experimental period, whereas the high-fat group (without purple corn extract) was significantly greater than the regular diet alone, the purple-corn-extract group, and the high-fat-plus-purple corn extract group during the last 8 weeks of the trial. Also noteworthy, all the fat depots measured were markedly greater in the high-fat group than in the mice on the regular diets, whereas dietary purple corn extract suppressed the high-fat-diet-induced increase in the adipose tissue depots. Adipose tissue weights in the high-fat-plus-purple corn extract group did not differ from those consuming the regular diet.

Some of the same authors who did much of the work reported above2 reported on a microarray-gene-expression profiling in human adipocytes treated with the anthocyanins C3G or Cy (cyanidin).7 They found a greater than 1.5-fold increase in the expression of adiponectin (remember that it improves insulin sensitivity, a good thing) and a greater than 1.5-fold decrease in the expression of plasminogen activator inhibitor-1 (increased plasminogen activator inhibitor-1 is associated with both obesity and type 2 diabetes and promotes thrombosis). Another gene downregulated by more than 1.5-fold was IL-6, a cytokine secreted by fat cells. It regulates acute-phase immune response and is elevated in obese and type 2 diabetes patients. Chronic IL-6 excess is associated with inflammation and has a detrimental effect on muscle strength,8 and its administration to humans is reported to increase fasting plasma glucose levels.

The Reaper May Not Win

Ingmar Bergman’s 1957 movie The Seventh Seal, while a manifesto for existentialism, which is not my cup of tea, presents an interesting allegory. The skillfully-crafted story centers around a 14th century knight named Antonius Block and his ongoing game of chess with a shadowy, hooded figure: Death (The Reaper). Bergman uses this parable not just to anthropomorphize death, but to illustrate the lengths that a man will go to in order to avoid it.

At the end, however, Death is a much better player, and though he may humor some of his opponents allowing them think that they have the advantage, the end result is inevitable: Death always wins.

But death does not always “triumph.” This can be confirmed by the continuous increase in lifespan, with life advancing over death, especially in the developed nations. And now with supplements such as purple corn extract, we can plan our moves, determined that we will win, and perhaps beat Death for the meanwhile, and the meanwhile … and the meanwhile.

References

  1. Kang MK, Li J, Kim JL, Gong JH, Kwak SN, Park JH, Lee JY, Lim SS, Kang YH. Purple corn anthocyanins inhibit diabetes-associated glomerular monocyte activation and macrophage infiltration. Am J Physiol Renal Physiol 2012 Jul 11. [Epub ahead of print]
  2. Tsuda T, Ueno Y, Aoki H, Koda T, Horio F, Takahashi N, Kawada T, Osawa T. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem Biophys Res Commun 2004 Mar 26;316(1):149-57.
  3. Cevallos-Casals BA, Cisneros-Zevallos L. Stoichiometric and kinetic studies of phenolic antioxidants from Andean purple corn and red-fleshed sweet potato. J Agric Food Chem 2003 May 21;51(11):3313-9.
  4. Tsuda T, Watanabe M, Ohshima K, Norinobu S, Choi S-W, Kawakishi S, Osawa T. Antioxidative activity of the anthocyanin pigments cyanidin 3-O-b-D-glucoside and cyaniding. J Agric Food Chem 1994;42:2407–10.
  5. Kähkönen MP, Heinonen M. Antioxidant activity of anthocyanins and their aglycons. J Agric Food Chem 2003 Jan 29;51(3):628-33
  6. Tsuda T, Horio F, Uchida K, Aoki H, Osawa T. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr 2003 Jul;133(7):2125-30.
  7. Tsuda T, Ueno Y, Yoshikawa T, Kojo H, Osawa T. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem Pharmacol 2006 Apr 14;71(8):1184-97.
  8. Maggio M, Guralnik JM, Longo DL, Ferrucci L. Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 2006Jun;61(6):575-84.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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