Inflammation, Cancer, Targets of Ginseng

A word of warning about using Ginseng:

If you are diabetic it is ill advised. Ginseng has a remarkable affect on the adrenal glands and this may impact on sugar regulation. Always consult your doctor before using Ginseng.

Ginseng is known to interfere with the actions of various pharmaceutical drugs.

Ginseng should not be used on a continual basis, it can induce adrenal exhaustion.


Article: Inflammation, Cancer, and Targets of Ginseng
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Authors: Lorne J. Hofseth and Michael J. Wargovich
Journal: J. Nutr. 137: 183S–185S, 2007.
Location: Life\Nutrition\Title
Date obtained: 18/10/2008
Date Read: 21/10/2008
Date to Review:
Web Page:
Keywords:
Printed:
Notes:
Abstract
Chronic inflammation is associated with a high cancer risk. At the molecular level, free radicals and aldehydes, produced during chronic inflammation, can induce deleterious gene mutation and posttranslational modifications of key cancerrelated proteins. Other products of inflammation, including cytokines, growth factors, and transcription factors such as nuclear factor kB, control the expression of cancer genes (e.g., suppressor genes and oncogenes) and key inflammatory enzymes such as inducible nitric oxide synthase and cyclooxygenase-2. These enzymes in turn directly influence reactive oxygen species and eicosanoid levels. The procancerous outcome of chronic inflammation is increased DNA damage, increased DNA synthesis, cellular proliferation, disruption of DNA repair pathways and cellular milieu, inhibition of apoptosis, and promotion of angiogenesis and invasion. Chronic inflammation is also associated with immunosuppression, which is a risk factor for cancer. Current treatment strategies for reactive species overload diseases are frequently aimed at treating or preventing the cause of inflammation. Although these strategies have led to some progress in combating reactive species overload diseases and associated cancers, exposure often occurs again after eradication, treatment to eradicate the cause fails, or the treatment has long-term side effects. Therefore, the identification of molecules and pathways involved in chronic inflammation and cancer is critical to the design of agents that may help in preventing the progression of reactive species overload disease and cancer associated with disease progression. Here, we use ginseng as an example of an antiinflammatory molecule that targets many of the key players in the inflammation-to-cancer sequence. J. Nutr. 137: 183S–185S, 2007.

TABLE 1 Key players in the inflammation-to-cancer sequence1
The inflammatory player: Examples of mechanisms toward carcinogenesis
RONS, COX, and NOS Damage DNA, modify cancer protein, alter proliferation and
apoptosis (depending on concentration, microenvironment, and genetic background
of target cells), inactivate tumor suppressor pathways (e.g., pRb and p53).
NF-kB Activate proliferation and inhibit apoptosis by activating modulators of these
event: cytokines (e.g., TNF-a), growth factors, survival genes (e.g., Bcl-XL),
angiogenic factors (e.g., VEGF), inflammatory genes (e.g., COX and NOS). Recent
high profile studies indicate this molecule is a key molecular node in the
inflammation-to-cancer sequence (2).
TLRs Activate MAP kinase and NF-kB pathways.
Cytokines Activate or deactive many inflammation and cancer pathways (1). Example:
The proinflammatory cytokine, IL-6 can antagonize p53, inactivate pRb, and activate
survival genes (Bcl-2 and Bcl-XL); The antiinflammatory cytokine, IL-10, can inhibit
proliferation and ras signaling.
Growth factors Transforming growth factor-b, at high concentrations, activates
p21/p27-mediated growth arrest and smad- and p53-mediated apoptosis.
MMPs MMP-2 promotes proliferation by activation of the discoidin domain tyrosine
kinase receptor 2. MMPs also are immunomodulators and stimulate angiogenesis,
inhibit cell adhesion, and inhibit apoptosis.
PPARs PPAR-g ligands are mostly protective to the inflammation- to-cancer sequence.
They inhibit iNOS, COX-2, NF-kB, MMPs, and E2Fs; they activate p53, p27, and p21.
Kinase pathways p38 stimulates proliferation and inhibits apoptosis. An inhibitor of
MAP kinase signaling (CNI-1493) has shown promise in ameliorating Crohn disease
in humans (3).
p53 and pRb pathways Both pathways are inactivated in reactive species overload
diseases (4,5).

Studies indicate that ginseng has potential as a chemopreventive agent or adjuvant treatment. Some of the cancers shown to decrease significantly with ginseng use include cancersof the pharynx, stomach, liver, pancreas, and colon (22,23). Mechanisms include inhibition of DNA damage (24), induction of apoptosis (25), and inhibition of cell proliferation (26). It is also becoming increasingly clear that ginseng has potent effects on the inflammatory cascade and may inhibit the inflammationto- cancer sequence.
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Ginseng targets the inflammatory players There is evidence that ginseng has potent effects on key players in the inflammatory cascade (Fig. 1). For example, ginsan, a polysaccharide extracted from P. ginseng, showed inhibition of s, the p38 MAP kinase pathway, and NF-kB in vitro and inhibition of proinflammatory cytokines in vivo (27). The ginsenoside Rg3 was shown to inhibit phorbol ester–induced COX-2 and NF-kB induction (28). BST204, a fermented ginseng extract, can inhibit inducible NOS (iNOS) expression and subsequent nitric oxide production from lipopolysaccharidestimulated RAW264.7 murine macrophages.

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Ginseng can also inhibit other mediators of the inflammation- to-cancer sequence, such as matrix metalloproteases and kinase pathways (31).
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Aussies and Iodine

Some may recall the time when table salt was fortified with iodine. Today that product seems rather hard to find and perhaps it is academic because so many people shy away from salt.

In this study they found a worryingly high percentage of Aussies had low iodine. A huge 43% were found to be iodine deficient. In relation to children and pregnant women this is potentially a very serious problem. Lack of iodine in children can lead to cognitive impairments and a range of other issues, in adults it can induce goiter. Iodine is essential for proper functioning of the thyroid, a gland that plays a regulatory role in the general rate of metabolism.

Food Standards Australia has released this report.

Sources of iodine:

Iodised Salt.
Seafood products.
In Australia, iodine fortified bread should be available in September 2009.

For an overview of iodine, recommended intakes and sources of iodine read this report from Nutrition Australia.

Bottled Water is Bollocks

Why the trend in bottled water became so prevalent was beyond me until I heard reports about the quality of drinking water in some parts of the world. Nonetheless, in most First World Countries tap water is of sufficient quality that we should not be wasting our money on bottled water. Unless of course we want to impress our friends ...

Numerous studies on bottled water have raised serious questions about the value of the product and this latest study adds further weight to the claim that bottled water is largely a waste of money. It can be summarised as follows:

• Bottled water is no guarantee that the water is contaminant free. Indeed many companies will not release their own testing results of the water you buy.
• The promotional images of bottled water are very misleading, bottled water is often municipal tap water that has been purified but still contains contaminants.
• Some bottled water even contained contaminants in excess of the safe recommended levels.
• Some bottled water was indistinguishable from tap water.

You can read the full report here.

There are another important considerations in relation to bottled water. It requires plastic bottles and you may recall all the fuss recently concerning bisphenol A, a very common component in plastic bottles, is now being found to have a wide range of potentially very unpleasant health consequences. For more information this link to an earlier post of mine might help.

If only that were all. The other issue in relation to bottled water is that the manufacturing and distribution of the this product is a coal burning exercise. Even if one is doubtful concerning Global Warming, the delivery of bottled water in plastics and by transport is terribly inefficient compared to water from the tap, especially given that there is on likely benefit drinking bottled water over tap water.

Antioxidants, Neurodegeneration, and Cancer

Research article. Interesting but lacking depth. Good balance on the issue of antioxidant supplementation.

The study can be downloaded here.

Article:
The role of antioxidant supplement in immune system, neoplastic, and
neurodegenerative disorders: a point of view for an assessment of the
risk/benefit profile
Authors:
Daria Brambilla, Cesare Mancuso,Mariagrazia Rita Scuderi,Paolo Bosco,Giuseppina Cantarella, Laurence Lempereur, Giulia Di Benedetto, Salvatore Pezzino, Renato Bernardini,
Journal: Nutrition Journal 2008, 7:29 doi:10.1186/1475-2891-7-29
Location: Life\Nutrition\title
Date obtained: 3/10/2008
Date Read: 19/10/2008
Date to Review:
Web Page:
Printed:
Notes:
Abstract
This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.
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However, several clinical studies demonstrated that not only malnutrition, but also the excess of certain nutrients (e.g. iron, alphatocopherol, beta-carotene, ascorbic acid) may set into motion oxidation phenomena and, therefore, cell injury [8,9]. Thus, it is of relevance that prior to considering introducing antioxidant therapy into mainstream medicine, significant advances in basic cell biology, pharmacology and clinical bioanalysis will be required.
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Heme oxygenase is a microsomal enzyme which metabolizes heme into ferrous iron, carbon monoxide and biliverdin (BV); the latter is then reduced by BVR into bilirubin (BR), a molecule endowed with strong antioxidant and antinitrosative activities [11-14]. Interestingly, all these protective factors act in a concerted way, enhancing the antioxidant defense system of the cell. When the balance between ROS/RNS and antioxidants turns in favor of the former, oxidative/nitrosative stress occurs.
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Extracellularly generated ROS can diffuse through anion channels into the cytoplasm; the resulting variation in the cell redox state leads to modulation of an array of transcription factors (eg. NF-kB, AP-1), protein kinases (e.g. AKT, JNK, p38), and receptor activated MAP kinases involved in apoptosis [17, 24,25,26]
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However, not only immune cell produce ROS necessary for the microbicidal activity, but they are also sensitive to external ROS, due to their high polyunsaturated fatty acids (PUFA) content. Immune cells are atypical, as compared with other somatic cells, in that they contain high levels of antioxidant vitamins, presumably providing protection against lipid peroxidation and immunosuppression, both of which are well known risks posed by high PUFA content [38].
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Intriguingly, the combined treatment with wheat germ and vitamin C profoundly inhibited metastasis formation in various tumor models of different origin (Lewis lung carcinoma, B16 melanoma and human colon carcinoma xenografts [HCR25]) [61].
61. Hidvégi M, Ráso E, Tömösközi-Farkas R, Paku S, Lapis K, Szende B: Effect of Avemar
and Avemar + vitamin C on tumor growth and metastasis in experimental animals.
Anticancer Res 1998, 18(4A): 2353-2358.
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Heme oxygenase-1, the inducible isoform of HO, is a key protein in the cell stress response and its up-regulation is a common event during pro-inflammatory conditions [11,69-72]. Recent work clearly demonstrated that regulatory T cells overexpress HO-1 and release CO under pro-oxidant conditions. Carbon monoxide may inhibit the proliferation of effector T cells, thus reducing the immune response and prevent autoimmunity and/or graft reaction [73,74]. Dietary antioxidants, in particular polyphenols, has been shown to increase HO-1 expression in different in vitro systems [3,75,76] and the potential use of this natural substances to regulate immune response should be carefully addressed.
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Other studies report that combination of vitamin A and other antioxidants, significantly increases mortality related to neoplastic diseases. [91]. According to these studies, selenium would be the only element displaying beneficial effects, as it has been shown that it reduces total cancer incidence, an apparently sex-related effect, as it is predominant among males, rather than in females [89].
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Due to their scarce bioavailability, only a negligible amount of polyphenols reaches brain tissue and the concentrations achieved are much lower than those efficacious in vitro [3]. As far as NSAIDs, ad hoc designed clinical trials with a large number of patients, clearly demonstrated that these drugs do not have any significant effect in slowing cognitive decline in patients suffering from mild-to-moderate AD [120,121].
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It is noteworthy to underlie that as for all drugs, antioxidants may give important side effects if not correctly used or in combination with other drugs. Vitamin A, E and â-carotene for instance, have been shown to have pro-oxidant effects at higher doses or under certain conditions [39].
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Exercise and Brain Aging

There is now abundant research pointing to the beneficial effects of aerobic exercise on cerebral health. This recent study finds that taking up exercise can improve cognition and cerebral health. There is a striking relationship between cardiovascular and cerebral health. The reason for this is obvious: the brain consumes approximately 20% of our oxygen intake, so maintaining maximal blood supply to the brain is critical. One of the reasons Ginkgo Biloba works is because it reduces platelet activating factor, thereby improving cerebral circulation.

Exercise and do it often. You don't have to run marathons, in fact intense exercise can do more harm than good. Light exercise is okay but it is important to push yourself, just going for a casual walk is good but going for a brisk walk is much better.

Exercise effects on cognitive and neural plasticity in older adults
Kirk Erickson and Arthur F Kramer
British Journal of Sports Medicine (2008).
The abstract:

Older adults frequently experience cognitive deficits accompanied by deterioration of brain tissue and function in a number of cortical and subcortical regions. Because of this common finding and the increasing aging population in many countries throughout the world, there is an increasing interest in assessing the possibility that partaking in or changing certain lifestyles could prevent or reverse cognitive and neural decay in older adults. In this review we critically evaluate and summarize the cross-sectional and longitudinal studies that assess the impact of aerobic exercise and fitness on cognitive performance, brain volume, and brain function in older adults with and without dementia. We argue that six-months of moderate levels of aerobic activity are sufficient to produce significant improvements in cognitive function with the most dramatic effects occurring on measures of executive control. These improvements are accompanied by altered brain activity measures and increases in prefrontal and temporal grey matter volume that translate into a more efficient and effective neural system.

Low antioxidant status and high sunlight exposure = Retinal Degeneration

I don't know if the below is a true statement because I have never heard it before but it does highlight why even blue light is damaging to vision. Lesson: obtain sunnies with blue light filtering capacity. Take it as high risk that by the time you reach 70 there is a distinct possibility you have some degree of cataract formation and retinal degeneration. The key is to contain the progress of these conditions as much as possible. That can be done but even with the best of care some of us are going to need cataract surgery and may develop AMD. Genes! In particular, a diet specifically addressing the oxidative balance in your blood is very important.

Most importantly control cholesterol, I have seen enough research to indicate that high cholesterol, particularly the small LDL variant (vLDL), readily penetrates the Retinal Pigment Epithelium and thus sets off unwanted cascades of nasties.

http://www.sciencedaily.com/releases/2008/10/081013171431.htm

... The eye is particularly vulnerable to the damaging effects of sunlight. Ultraviolet radiation is absorbed by the lens, but visible or “blue” light penetrates to the retina so allowing us to see. Protection against the harmful effects of blue light is provided by the antioxidant vitamins C and E, the carotenoids (lutein and zeaxanthin) which filter blue light, and zinc. --------

The Aging Brain

This study from the Neurobiology of Aging highlights the significance of white matter in the aging process of the brain. The news item can be read here. White matter is the extensive sheath that surrounds the long and not so long axons of nerve cells. The presence of white matter markedly improves the speed at which signals can traverse through long axons. The process of myelination is long and we can in our late 20's or even early 30's before this process is completed.



Myelin creation is not a one off event, it is subject to continual degradation and renewal. The cells that produce myeline are called oligodendrocytes, a type of glial cell. Unfortunately oligodendrocyte cells demonstrate some particular vulnerabilities to insult. In those with Multiple Sclerosis, a common autoimmune condition, the immune processes responds to various "danger signals" emitted by oligodendrocytes and this can establish an ongoing destruction of these cells and myelin production. The initial triggers for this condition remain unknown but there are a number of strategies that Multiple Sclerosis sufferers can undertake which may alleviate the progress of the condition.

As we age the balance between myelin degradation and renewal falls out of kilter, the result being that we start losing the myelin covering. Of interest is the association between dementias and changes in white matter, it may even be the case that in some individuals the destruction of myelin is so extensive as to initiate a series of inflammatory processes that in turn induce dementias.

There is an important lesson here. The brain controls the body, maximising cerebral health is critical to maintaining good health as we age.

Lipofuscin And Aging

Lipofuscin is the deposition of waste products in the cell that are not degraded. The critical factor seems to be rate at which proteins and lipids are degraded by the various "house keeping" functions in the cell. In these days the emphasis on the dynamics of aging is typically excessive oxidation events and lipofuscin receives little attention. Lipofuscin is something that needs to be addressed because as lipofuscin deposits increase the cell becomes increasingly unable to do its job.

In the graphic below I have extracted a table from a very old study. It highlights the huge increase in lipofuscin aggregation with age. They used acetyl l carnitine has a therapeutic intervention and the results were quite good but only at very high dosages. Other and much more recent research has found that acetyl l carnitine can also play an important role in preventing Age Related Macular Degeneration (AMD). In those studies they created a compound called Phototrop, a combination of acetyl L carnitine, omega 3 fatty acids, and co-enzyme Q10.

Word of warning: you should always use alpha lipoic acid with ALC because ALC increases mitochondrial function and mitochondria are the key region where oxidants are formed.

The table below is from

Japan J Pharmacol, 38, 365-71(1988)

Another worrying study concerning mobile phones

There are now a number of studies pointing to the dangers of mobile phones. Of particular concern is the widespread and frequent use of mobile phones amongst teenagers. This study reveals a disturbing quality about the microwave radiation emitted from mobile phones: the markers of oxidative stress, MDA(malondialdehyde) and XO(xanthine oxidase) remain up to 40 days after exposure to the microwave radiation in a rat model. One factor causing this sustained expression of inflammatory markers was the persistent reduction in catalase, a key antioxidant pathway in our cells.

Previous research has found increased risk of brain tumours in the young. While the telecommunications industry strenously denies any danger from using mobile phones increasing research is painting a very different picture. Some authorities have even claimed that the widespread use of mobile phones is paving the way for an epidemic of brain tumours.

Thanks to Dr. Lefever for forwarding this study to me.

The full study can be downloaded here.

Electric Eels and Electronic Implants

This study from Nature Nanotechnology is fascinating. They claim to have found a way to model the cells in electric eels that create electricity so that artificial cells can be used to power medical implant devices.

The news item can be read here.