Blueberries in the fight against Alzheimer's Disease. What is the evidence?

You may have heard in the popular media that blueberries are a potential panacea for many health conditions including memory and cognitive complaints. Blueberries do indeed seem to be beneficial for ones health however we need to establish the proven limits of these benefits. As this blog focuses on Alzheimer's disease and dementia we will look at the available evidence to determine whether blueberries are worth it in the fight against these diseases.

Unfortunately there is not a lot of human research involving blueberries and either Alzheimer's disease or dementia. There were only two that I could find. In one very small study of 9 elderly adults with early memory changes consumption of blueberry juice daily for 12 weeks improved paired associate learning and word list recall (Krikorian et al, 2010). A much larger epidemiological study of more than 16000 elderly adults found that greater intakes of blueberries was associated with slower rates of cognitive decline (Devore et al, 2012). These studies only support the effects of blueberries for age related cognitive decline and not specifically for Alzheimer's disease or dementia.

There are numerous animal studies that show that supplementation with blueberry extract can prevent or improve cognitive decline in older rats and mice (Malin et al, 2011. Krikorian, Shidler et al, 2010. Andres-Lacueva et al, 2005. Shukitt-Hale et al, 2005). Most of these studies attribute this to the antioxidant effects of the blueberry polyphenols. In a promising study of mice genetically engineered to develop Alzheimer's disease the addition of blueberries to the diet from a young age not only did not develop cognitive deficits seen with the disease but also showed normal levels of Amyloid beta burden into adulthood (Arendash et al, 2003). These effects seen against amyloid beta are supported by two other studies. The first study showed that pretreatment of hippocampal neuronal cells with a blueberry extract reduced the ability of amyloid beta to cause disfunction (Joseph et al, 2007). The second study was conducted in mice and showed that the addition of a blueberries to the diet had a three fold effect of (Zhu et al, 2008):

1. Increasing the clearance of amyloid beta by microglial cells
2. Reducing the aggregation of amyloid beta and hence plaque formations
3. Suppression of pro-inflammatory activity by microglial cell

This is very promising as it demonstrates at least 4 potential mechanisms (including antioxidant properties) by which blueberries could be active against Alzheimer's disease.

This is not however where the potential cognitive benefits blueberries end. There is also preliminary evidence that blueberries may be neuro-protective and enhance plasticity (and hence memory and learning). Three studies in mice examined the effects of blueberry supplementation on specific brain chemicals. All three found that the mice consuming the blueberries had higher levels of brain derived neurotrophic factor (BDNF) (Rendeiro et al, 2013 and 2012. Williams et al, 2008). BDNF is like fertiliser for neurones. It stimulates the growth and formation of new connections which is the basis for learning and memory. Essentially the higher BDNF the faster you learn. In addition to this there are several studies showing that blueberries improve the survivability of neurons. In all of these studies neurons were exposed to a stressor (light, stroke, inflammation). Those neurons exposed to the blueberry extract before the stressor were more likely to survive and be functional than those that were not indicating blueberry's role in protecting from various sources of damage (Tremblay et al, 2013. Galli et al, 2006. Sweeney et al, 2002).

In conclusion blueberries certainly appear to have the ingredients necessary to effectively combat Alzheimer's disease. Most of these effects are only preliminary and have not been studied in human models. It is therefore impossible to say that blueberries would be efective for Alzheimer's patients or even the prevention of such diseases with further extensive studies. That said blueberries are a food item that is safe and also part of a healthy diet. Including them as a in your diet is beneficial on a general health perspective and may have the added benefit of preventing or treating Alzheimer's disease. However for now we can't be certain.

Click on blueberries for cognitive enhancement for more information

1. Blueberry Supplementation Improves Memory in Older Adults (Krikorian et al, 2010)
2. Dietary intakes of berries and flavonoids in relation to cognitive decline (Devore et al, 2012)
3. Short-term blueberry-enriched diet prevents and reverses object recognition memory loss in aging rats (Malin et al, 2011)
4. Blueberry supplementation improves memory in older adults (Krikorian, Shidler et al, 2010)
5. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory (Andres-Lacueva et al, 2005)
6. Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress (Shukitt-Hale et al, 2005)
7. Blueberry Supplementation Enhances Signaling and Prevents Behavioral Deficits in an Alzheimer Disease Model (Arendash et al, 2003)
8. Dopamine and Aβ-Induced Stress Signaling and Decrements in Ca^{2+} Buffering In Primary Neonatal Hippocampal Cells Are Antagonized by Blueberry Extract (Joseph et al, 2007)
9. Blueberry Opposes β-Amyloid Peptide-Induced Microglial Activation Via Inhibition of p44/42 Mitogen-Activation Protein Kinase (Zhu et al, 2008)
10. Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor (Rendeiro et al, 2013)
11. Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats (Rendeiro et al, 2012)
12. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels (Williams et al, 2008)
13. Prophylactic neuroprotection by blueberry-enriched diet in a rat model of light-induced retinopathy (Tremblay et al, 2013)
14. Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection (Galli et al, 2006)
15. Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage (Sweeney et al, 2002)

Red Wine and Green tea Polyphenols: Blocking Beta Amyloid

One of the principle ways in which Alzheimer's disease causes destruction in the brain is via accumulation of beta amyloid proteins. It is the presence of these proteins (via several different methods) that results in the death of neurons. New research sheds light on one of the possible pathways by which beta amyloid causes Alzheimer's disease. This study also demonstrates that the polyphenols found in green tea and red wine may be able block this particular pathway.

The study from the Journal of Biological Chemistry (1) demonstrated in a cellular model how the beta amyloid present outside of neurons could bind with surface receptors in order to be drawn into the cell. The continuous internalization of  beta amyloid results in functional deficits and eventually the death of the neuron. This perpetuates a positive feedback loop that leads to disease as explained in my previous post "Why Alzheimer's Disease happens: Targets for slowing, stopping and reversing Alzheimer's disease."

In addition to analysing the process of beta amyloid binding and internalization, the study also examined what would happen if green tea (EGCG) or red wine (resveratrol) extracts were added in with the beta amyloid and neurons. The results demonstrated that EGCG and resveratrol could bind to and change the configuration of the beta amyloid protein. This had the effect of reducing the ability of the beta amyloid to bind to the neuron surface and become internalized. In essence these extracts removed beta amyloid toxicity.

The anti-alzheimer's effects of green tea have been talked about already here, here and here. This study advances our understanding of how it may interact with beta amyloid. Resveratrol has not been covered in this blog but is now an exciting prospect for further comment. As usual though this study was only conducted in cells in the lab. Whether EGCG and resveratrol actually have this effect within the human brain will not be known until tests to examine this are conducted.

1. Prion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1. Jo V. Rushworth, Heledd H. Griffiths, Nicole T. Watt and Nigel M. Hooper. (2013) Journal of Biological Chemistry 

Slowing the Progression of Alzheimer's Disease Using Panax Ginseng. What the Science Says.

Most people have probably heard of ginseng before. In fact it is often added to energy drinks and sport supplements to enhance stamina and endurance. For those that aren't familiar with it ginseng is used to refere to any of 4 different plant species used in traditional medicines as adaptogens. "What the hell is an adaptogen?" I hear you ask. Well basically an adaptogen is traditionally a herb or supplement that helps the mind and body adapt and cope with stressful situations. The four types of ginseng are commonly referred to by there geographical location and include Korean, Siberian, American and Indian. All of them are very interesting herbs however for this post we will concentrate on Korean ginseng (Panax Ginseng) as it is probably the most extensively studied.

So the big question here is does Panax Ginseng have any anti-Alzheimer's activity? The answer to that question appears to be yes. In a 2008 study by Lee et al Alzheimer's patients were assigned either a ginseng supplement or a placebo. The supplement consisted of 4.5g per day of Panax Ginseng root powder and was given to 58 patients. The placebo was given to 39 patients. The study lasted for 24 weeks (12 weeks of supplementation followed by 12 weeks without). Cognitive performances were monitored using the mini-mental state examination (MMSE) and Alzheimer disease assessment scale (ADAS). After ginseng treatment, the cognitive subscale of ADAS and the MMSE score began to show improvements and continued up to 12 weeks. After discontinuing ginseng, the improved ADAS and MMSE scores declined to the levels of the control group. This demonstrated that panax ginseng may be effective in not just halting the progression of Alzheimer's disease but even reversing some of its effects (At least over a 12 week period). These results were confirmed by another study by Heo et al. They essentially repeated the above study and also used a 9g dose of panax ginseng root powder. This 9g dose was shown to improve cognitive measures in the Alzheimer's patients compared to the placebo group. Both of these studies show a lot of promise however larger studies would be required to really confirm these benefits. So for now what other evidence can we find for and against panax ginseng?

There are more clues as to how panax ginseng could be beneficial for Alzheimer's disease sufferers. Firstly it appears to be neuroprotective by preventing neurons from undergoing programmed cell death (apotosis). Two studies, one animal and cellular (1, 2), demonstrate how administration of panax ginseng can protect neurons from dying when exposed to stressful and damaging environments. In addition to this a cellular study on rat brains (3) showed that addition of panax ginseng saponins could reduce the functional defects caused by beta amyloid accumulation in and around neurons. These researchers followed up this study by injecting beta amyloid into the brains of rats to induce Alzheimer's like symptoms of amnesia (4). Chronic administration of ginseng saponins was shown to significantly reverse the amnesia caused by the beta amyloid confirming the results from the first study only in a working animal model. It is not yet understood how the panax ginseng reverses neuronal defects caused by beta amyloid. It is clear that ginseng did not eliminate the beta amyloid and so its effects must have occurred through a different mechanism. This is useful to know as it points to another possible mechanism by which to attack Alzheimer's disease. For the time being panax ginseng is a promising potential treatment for Alzheimer's disease and in combination with other strategies or supplements could indeed be very complimentary.

1. Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Liao B, Newmark H, Zhou R, Experimental Neurology [2002, 173(2):224-234]
2. Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia. Guizhi Zhang, Ailing Liu, Yingbin Zhou, Xun San, Taowei Jin, Yi Jin. Journal of Ethnopharmacology, Volume 115, Issue 3, 12 February 2008, Pages 441–448
3. Effect of ginseng saponins on beta-amyloid-suppressed acetylcholine release from rat hippocampal slices. Lee TF, Shiao YJ, Chen CF, Wang LC. Planta Med. 2001 Oct;67(7):634-7.
4. Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides. Chen F, Eckman EA, Eckman CB. FASEB J. 2006 Jun;20(8):1269-71.

Blood Pressure, Alzheimer's Disease and Dementia: Some alternative therapies

Blood pressure gauge
Originally uploaded by stephanebenito

We know that both Alzheimer's disease and dementia are complex diseases that result from a culmination of several different triggers. One trigger that people are often surprised to know increase your risks of both Alzheimer's disease and dementia is high blood pressure. So what US health authorities are now doing is testing to see if current blood pressure drugs have the ability to slow or even reverse Alzheimer's disease and dementia. This is an encouraging change from trying to cover up symptoms to actually addressing the underlying causes. However as i continually note this is only one part of the disease system all of which will need addressing to beat Alzheimer's disease or dementia.

So lets start with a little recap on the ability of high blood pressure (also known as hypertension) to contribute to Alzheimer's disease and dementia. Firstly when you have high blood pressure this puts mechanical stress on the blood vessels. This causes damage to them which results in two responses. Formation of free radicals and inflammation. Both these things are underlying causes of Alzheimer's disease and dementia and in particular vascular dementia. So it is easy to see how reducing blood pressure could aid Alzheimer's disease and dementia. High blood pressure however is not the sole cause of inflammation and free radical generation in Alzheimer's disease and dementia which is why other strategies are also needed.

That said it will not hurt to reduce your blood pressure. So how do we go about doing that? Well you could go to your doctor and request anti-hypertension drugs. This could work but may be expensive and be accompanied by unpleasant side effects. Omega 3 fatty acids and cocoa have proven blood pressure lowering effects.

Numerous double blind placebo controlled experiments have been conducted in humans using omega 3 oils. These consistently show that it reduces high blood pressure while at the same time improving blood pressure control. In addition to this omega 3 has significant anti-inflammatory and antioxidant properties.

Cocoa is what we make chocolate out of. It is extremely rich in antioxidant flavanols some of which have antihypertensive properties similar to current pharmaceutical drugs. One very recent study in 50 people with mild hypertension showed that consumption of cocoa flavanols over a 6 week period significantly reduced blood pressure. Doses required to achieve this reduction were high.

Do yourself a favor and start eating more fish and dark chocolate. Not only can they reduce blood pressure but they also are antioxidant and anti-inflammatory. Perfect for beating Alzheimer's disease and dementia.

How Green Tea Beats Alzheimer's Disease: Part 3 (Beta Amyloid)

Manicured landscape, Sri Lanka
Originally uploaded by Yvon from Ottawa

So here comes part 3 of this series about green tea and Alzheimer's disease. As i have mentioned before green tea and its polyphenols are one of the best known anti Alzheimer's disease and dementia treatments out there. The reason for this is its multi-action approach.

Alzheimer's disease is complicated and so relying on single strategies like the pharmaceutical companies do is plain stupid. So why don't the drug companies sell green tea? Easy, they can't patent its contents and so cannot make money from it. This is good for us because not only it green tea better than any current Alzheimer's disease and dementia drugs but it is also significantly cheaper and safer.

So after green tea's metal chelation and anti-oxidant activities what is activity number 3? I bet you didn't guess anti-beta amyloid. "You are probably saying anti-beta what?" Well i don't blame you. Beta amyloid is a protein that forms clumps in the brain. This then leads to numerous other problems culminating in neuron death. Basically all you need to know is that without beta amyloid there is no Alzheimer's disease.

So how do we stop it forming or get rid of it once it does? For the purposes of this post green tea is one convenient answer. There are several studies in mice with Alzheimer's disease shows that giving them the main active green tea polyphenol called epigallocatechin-3-gallate (EGCG) in drinking water decreases levels of this beta amyloid by as much as 58% (see here).

The mechanism by which green tea does this is via preventing beta amyloid forming in the first place. It basically programs the neurons to produce healthy beta amyloid that does not form clumps. If clumps do not form the beta amyloid can be broken down and removed from the brain preventing its damaging effects.

This activity of green tea is significant. No drugs to date have this action let alone the metal chelation, antioxidant and the other actions i will save for other posts. So don't waste any time. Get your 5 cups per day of green tea for the best results.

Mediterranean Diet: One Key to Vascular Dementia Prevention

Vascular dementia is the second most common form of dementia behind Alzheimer's disease. However its cause is much different to that of Alzheimer's disease. Vascular dementia involves parts of the brain being starved of oxygen due to defects in blood vessels. So it may come as no surprise that the Mediterranean diet which is high in antioxidant and healthy fats has been shown to help prevent Vascular dementia.

A new study examined 712 people over the age of 65. These people were asked about their diet and then underwent an MRI 6 years later. Researchers found that those eating diets close to a Mediterranean diet were 36% less likely to have areas of brain damage associated with Vascular dementia. So lets examine the Mediterranean diet more closely to see why this is the case.

The Mediterranean diet includes a lot of fruit, vegetables, whole grains and legumes and healthy fats such as from fish and olive oil. It is also lower in saturated fats and cholesterol. So what does this mean? We know that saturated fats and cholesterol over time damage blood vessels and can lead to blockages that cause Vascular dementia. Fruits and vegetables contain many polyphenols. They protect against free radical damage which is another leading cause of vascular dementia. Both omega 3 fatty acids and olive oils help to keep the blood vessels clear of plaque and fat buildup that can block them. They also inhibit inflammation and so reduce the damage caused when the immune system reacts to plaque buildup. Finally whole grains and legumes are generally low GI (Glycemic Index). Low GI foods help maintain normal blood glucose/Insulin balance. This prevents formation of type 2 diabetes and also large sugar spikes both of which can cause damage to blood vessels and hence vascular dementia.

Not only is there evidence of the Mediterranean diet's ability to prevent vascular dementia as a whole but there is even more supporting evidence for all the components that make up the diet. Not only is the Mediterranean diet very healthy but it also tastes extremely good too. I encourage people to learn a few recipes. It will be well worth it.

The Secret to Preventing Alzheimer's Disease and Dementia. An Indian Case Study

When I look at research about Alzheimer's disease and dementia certain types of studies always attract my attention more than other. Sure experiments in the lab can provide us with valuable information but the fact still remains, it is in a lab not the real world. So every time studies emerge on real people and real places they provide real solid insights into Alzheimer's disease and dementia. The study that i will examine in this post comes from India. Well actually from a northern state called Haryana.

What is uniques about people from Haryana is that they have a rate of Alzheimer's disease that is a third of that compared to parts of Britain and the United States. In fact these people have the lowest rates of Alzheimer's disease in the world. Why? Maybe it could be genetic? Unlikely, researchers looked at the genetic profiles of people from Haryana and found that they were very similar to people in the rest of the world. There levels of the Alzheimer's causing gene were almost identicle. This leave only lifestyle factors.

Despite there being genes that are associated with Alzheimer's disease it is far and away a disease of lifestyle and it is these kind of studies that prove it. In the case of people from Haryana their diet consists of turmeric, omega 3 fatty acids, vitamins D and B12 and lots of high antioxidant containing fruits and vegetables. They also have lower cholesterol levels and consume less fat that other population. Also of equal importance is how they live their lives. They are farmers who remain very physically active but also lead simple stress free lives. From all my knowledge I can say these people almost live the perfect anti Alzheimer's lifestyle. Why?

Turmeric by itself shows powerful activity at preventing and even treating Alzheimer's disease. Omega 3 fatty acids are antioxidant, anti-inflammatory and have been shown to benefit Alzheimer's disease. Alzheimer's disease is a disease of excessive oxidative damage. High levels of antioxidant from fruit and vegetables can help here. Vitamin D deficiency is associated with lower levels of many disease including Alzheimer's disease and vitamin B12 is necessary for correct energy use in the brain. Cholesterol has been shown to contribute and even cause Alzheimer's disease as have diets high in fat. Stress causes oxidative damage to the brain while exercise protect and even stimulate brain growth and functioning.

If you want to know how to prevent or even treat Alzheimer's disease or dementia then many of the answers are here. This disease isn't as complicated as the medical industry would like us to believe. Good Luck.