Thursday, November 20, 2008

Diabetes and Pollution

To yet again highlight the ever increasing dangers of pollution, this article puts forward a very worrying hypothesis that is cause for concern. This is not the first study to find a link between diabetes and pollution and it will not be the last.

Potassium, Sodium, and Blood Pressure

Low Potassium is linked to high blood pressure

Most of us have heard about the dangers of excessive salt consumption in relation to blood pressure. While salt consumption needs to be carefully monitored it is equally as important to ensure that we receive adequate potassium intake. This can be quite a challenge as recommended potassium intake is quite high. Bananas, potatoes, Tomato juice, orange juice, are all good sources of potassium. This article, from the ever reliable NIH institute, provides a good overview of potassium and its dietary sources. Note the daily requirement for potassium is a whooping 4.7 grams. To achieve this, have a look at this site for more detailed guidelines on potassium dietary sources. Look at the table at the bottom of the page. They have excluded meat sources but these are also valuable sources of potassium.

Remember, the potassium - salt(ie sodium) balance is very important, so if you eat lots of processed food, which is typically far too high in sodium and\or salt, you need to counter balance this with substantial potassium intake.

Stop Killing the Frogs

There is a prevailing mythology that if bodily concentrations of a particular compound are below the "safety threshold" then no damage is being done. Even a basic understanding of biological processes should reveal how dangerous and misleading that notion is. As this recent indicates, cumulative exposure of various compounds that are well below the safety threshold for each compound are more than capable of killing amphibians. We should all be very worried about the amount of junk humanity is pouring into the environment because this has serious implications not only for the other animals but as increasing numbers of studies are indicating this also has serious implications for human health.

Marijuana and Dementia

Over the years there have been multiple studies indicating the potential of cannabinoids across a wide range of conditions. This latest study provides further weight as to the therapeutic potential of cannabinoids. It is high time that the public was made aware of the considerable therapeutic potential of these compounds. As for the psychosis\schizophrenia risk, that has been too much overblown and the risk is virtually negligible post 21 years of age. The reasons for this therapeutic potential are:

  • The two principal cannabinoids, THC and cannabidiol, have very strong antioxidant capacity.
  • These two compounds are lipophilic, that is lipid soluble, hence will remain in the body for extended periods. For pot smokers, typical wash out periods are 90% after one week, though this can greatly vary.
  • Both of these compounds target specific receptors. THC will target CB1 and to a lesser extent CB2(controversial), while cannabidiol is very specific for CB2 and hence is non-psychoactive.
  • Both compounds will bind to the anion site of ACHe, an enzyme that breaks down acetylcholine. This neurotransmitter is markedly reduced in some dementias, particularly Alzheimers.
  • ACHe is also strongly implicated in amyloid production, both cannabinoids reduce the production of amyloid, an early step in Alzheimers because this production seems contingent on the anion site.
  • Activation of the CB2 receptor limits the expression of pro-inflammatory cytokines, excess production of these cytokines being implicated in everything from atherosclerosis to cancer to dementia.

Sunday, November 9, 2008

Vitamin B3 and Alzheimers Disease

9/11/2008 4:37PM

Vitamin B3 and Alzheimers Disease

Nicotinamide is a form of Vitamin B3. This is a promising study because this compound was found to target a key and early initiator of amyloid plaque formation in the brain. That process is tau phosphorylation which is implicated in many neurodegenerative conditions. Nicotinamide can be purchased as supplement and is generally safe but at very high doses can be toxic.

The Science Daily news release is available here.

The Journal of Neuroscience, November 5, 2008, 28(45):11500-11510; doi:10.1523/JNEUROSCI.3203-08.2008
Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau
Kim N. Green,1 Joan S. Steffan,2 Hilda Martinez-Coria,1 Xuemin Sun,3 Steven S. Schreiber,3,5 Leslie Michels Thompson,1,2,4 and Frank M. LaFerla1
Departments of 1Neurobiology and Behavior, 2Psychiatry and Human Behavior, 3Neurology, 4Biological Chemistry, and 5Anatomy and Neurobiology, University of California, Irvine, Irvine, California 92697-4545
Correspondence should be addressed to Frank M. LaFerla, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, CA 92697-4545. Email:
Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated -tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability.

A "Fat Burning" Drug?

Experimental Drug Spurs Fat Burning

This is all becoming rather silly. That so many valuable research resources are being wasted on what is essentially a behavioral problem is a poor reflection on society and the state of biomedical research. The last fat burning drug promising miracles was fenfluramine. It was discontinued in 1997 because it was found to induce heart valve damage, this damage lasting years after use was ceased.

This drug targets SIRT1, a gene transcription regulator that is strongly associated with the beneficial effects of caloric restriction. A word of warning about the caloric restriction craze: recent studies have indicated that it will probably not prolong life in humans and it does carry some risks, including infertility, immunosuppression, hypoglycemia, and there is some suggestion it may damage the brain over the long term. Not surprising really, animals living in cages on CR is something entirely different from the real world experience. I suspect this drug will never reach the market.

To use drugs to address what is essentially a behavioral problem is both dumb and dangerous. Sure, it can be very difficult to lose weight. Many years ago I began to pile on the weight. It took time but I now have reduced my weight to a very good level. I could probably lose a few more kilos but I'm not obsessive about weight, in fact I think the Body Mass Index is silly and misleading. What many are loathe to say is that being a little overweight is probably better than being underweight. Some studies do support this.

If you are gaining weight don't run to the doctor for a magic bullet. In this age of ballooning health care costs and innumerable accounts of so called "scientifically tested" drugs proving to have worrying side effects prudence and common sense dictates that we should take charge of our health instead of seeking magic bullets from the biomedicine industry. You know what you have to do: change your lifestyle and diet. Don't try to lose weight quickly, don't diet, change your lifestyle and diet so the weight is gradually shed until you reach the weight you think is good for your body type. The BMI is a useful guide but don't take it as an absolute. There are no dietary or health secrets and anyone who tells you differently is probably trying to sell you something.

Antioxidants - A Risk Benefit Profile

Antioxidants are all the rage these days. Paradoxically, while there are many in vitro studies demonstrating potential benefits from antioxidants, and many studies indicating their utility in various pathologies, there is scant evidence that antioxidant supplementation prolongs life.

I have concerns about the absorbing huge doses of antioxidants. Oxidation is an intrinsic and vital physiological process, filling up your body with antioxidants may sound like a good idea but how often have we been subjected to the latest nutrition craze only to find that it was nonsense? Far too many times, there needs to be much caution in the use of antioxidants. This recent study highlights that while antioxidants have considerable therapeutic promise, indiscriminate use of antioxidants can also lead to pathological processes.

One thing not mentioned in this study but is very important is the use of alpha tocopherol, typically and misleading referred to as Vitamin E. There are in fact a number of types of vitamin E and high consumption of alpha tocopherol can reduce the concentrations of gamma tocopherol and delta tocopherol, both of which are better variants than alpha tocopherol. . This may explain why some studies have found that high dosages of alpha tocopherol can increase mortality. The reason why most vitamin E supplements only contain alpha tocopherol is simple: it is the cheapest to manufacture. If you want a good source of vitamin E use wheatgerm. Note what the below study found in relation to wheatgerm:

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]. On the contrary, wheat germ had no toxicity on peripheral blood leukocytes (PBLs) at doses that affected tumor cells. The crude powder extract of fermented wheat germ inhibits nucleic acid ribose synthesis primarily through the non-oxidative steps of the pentose cycle [60]. Curiously, another quinone compound, carnosic acid quinone, like wheat germ, recovers potent antioxidant activity upon standing [62].

Note that last sentence, that the antioxidants in wheat germ "recover" their antioxidant activity. Now whether or not this happens in the body is another question but given that wheat germ is cheap and a valuable nutrient source why bother with all those expensive supplements?

This study also highlights that certain antioxidants, at high doses, can actually induce oxidation. Ever since that now famous study on beta carotene which found it increased the rate of lung cancer in smokers(as if that were possible!) I have harbored suspicions that beta carotene should not be added to multi vitamins. Smokers should definitely avoid beta carotene in vitamin pills and problem be careful about the intake from natural sources. As for non smokers, the data is equivocal. Beta carotene does not appear to be a causative factor for or against developing cancer.

Ascorbic acid, a variant of vitamin C, appears to be a double edged sword. At high doses it can stimulate the production reactive oxygen species, particularly in the presence of free iron, the latter often being present in inflammatory conditions. Mega dosing of vitamin C is a waste of money and can damage the gut. Once tissue saturation of vitamin C is achieved there is little point in swallowing vitamin C tablets because it will not pass the gut wall. Smokers should increase their intake of vitamin C has it has been shown to help preserve vitamin E levels. As with most antioxidants, it is generally better to consume these throughout the day because this will help maintain tissue levels through the course of the day, whereas consuming antioxidant rich foods or supplements at one time of the day will lead to depletion until topping up occurs at the next meal.

The flip side of megadosing for vitamin C is recent studies which found that intravenous injections of vitamin C may have therapeutic use in treating some cancers.

The below study can be downloaded at this site.

The role of antioxidant supplement in immune system, neoplastic,
and neurodegenerative disorders: a point of view for an assessment
of the risk/benefit profile
Daria Brambilla1, Cesare Mancuso2, Mariagrazia Rita Scuderi1, Paolo Bosco3,
Giuseppina Cantarella1, Laurence Lempereur1, Giulia Di BenedettoLL0000001,
Salvatore Pezzino1 and Renato Bernardini*1
Nutrition Journal 2008, 7:29 doi:10.1186/1475-2891-7-29
Date obtained
Date Read
Date to Review
Web Page
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.