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Showing posts with label Flavonoid. Show all posts
Showing posts with label Flavonoid. Show all posts

Thursday, 26 February 2015

Inflammation Leading to Cognitive Dysfunction


Today’s post highlights a paper with some very concise insights into how microglial cells become “activated” resulting in the “exaggerated inflammatory response” that many people with autism experience on a daily basis.  

This is very relevant to treatment, which is not usually the objective of much autism research.

I recall reading a comment from John’s Hopkins about neuroinflammation/activated microglia in autism; they commented that no known therapy currently exists and that, of course, common NSAIDs like ibuprofen will not be effective.  But NSAIDs are effective.

As we see in today’s paper, there a least 4 indirect cytokine-dependent pathways leading to the microglia, plus one direct one.
NSAIDs most definitely can reduce cytokine signaling and thus, indirectly, reduce microglial activation.

The ideal therapy would act directly at the microglia, and as Johns Hopkins pointed out, that does not yet exist with today's drugs.  If you read the research on various natural flavonoids you will see that “in vitro” there are known substances with anti-neuroinflammatory effects on microglial activation.  The recurring “problem” with such substances is low bioavailability and inability to cross the blood brain barrier.


Back to Today’s Paper

It was a conference paper at the 114th Abbott Nutrition Research Conference - Cognition and Nutrition



The paper is not about autism, it is about more general cognitive dysfunction.  It is from mainstream science (I checked).

It explains how inflammation anywhere in the body can be translated across the BBB (Blood Brain Barrier) to activate the microglia.  This of course allows you to think of ways to counter these mechanisms.

It also raises the issue of whether or not anti-inflammatory agents really need to cross the BBB.  While you might think that ability to cross the BBB is a perquisite to mitigate the activated microglia, this may not be the case.  Much can be achieved outside the BBB, and we should not rule out substances that cannot cross the BBB.

Very many known anti-inflammatory substances do not cross the BBB.   

  



extracts from the above paper ...








Example – Influenza and Cognition

Neurological and cognitive effects associated with influenza infection have been reported throughout history.

The simplest explanation for these neurocognitive effects is that influenza virus makes its way to the brain, where it is detected by neurons.

However, most influenza strains, including those responsible for pandemics, are considered non-neurotropic, neurological symptoms associated with influenza infection are not a result of direct viral invasion into the CNS.

Moreover, neurons do not have receptors to detect viruses (or other pathogens) directly.

Cells of the immune system do, however, as the immune system’s primary responsibility is to recognize infectious pathogens and contend with them. For example, sentinel immune cells such as monocytes and macrophages are equipped with toll-like receptors (TLR) that recognize unique molecules associated with groups of pathogens (i.e., pathogen-associated molecular patterns). Stimulation of TLRs that recognize viruses (TLR3 and TLR7) and bacteria (TLR4) on immune sentinel cells can have profound neurological and cognitive effects, suggesting the immune system conveys a message to the brain after detecting an infectious agent. This message is cytokine based.

Macrophages and monocytes produce inflammatory cytokines (e.g., interleukin [IL]-1β, IL-6, and tumor necrosis factor-α [TNF-α]) that facilitate communication between the periphery and brain.


Cytokine-dependent Pathways to the Brain

Several cytokine-dependent pathways that enable the peripheral immune system to transcend the blood-brain barrier have been dissected.

Inflammatory cytokines present in blood can be actively transported into the brain.
But there are also four indirect pathways:-

1.     Cytokines produced in the periphery need not enter the brain to elicit neurocognitive changes. This is because inflammatory stimuli in the periphery can induce microglial cells to produce a similar repertoire of inflammatory cytokines. Thus, brain microglia recapitulates the message from the peripheral immune system.

2.     in a second pathway, inflammatory cytokines in the periphery can bind receptors on blood-brain barrier endothelial cells and induce perivascular microglia or macrophages to express cytokines that are released into the brain

3.     In a third pathway, cytokines in the periphery convey a message to the brain via the vagus nerve. After immune challenge, dendritic cells and macrophages that are closely associated with the abdominal vagus have been shown to express IL-1β protein; IL-1 binding sites have been identified in several regions of the vagus as well. When activated by cytokines, the vagus can activate specific neural pathways that are involved in neurocognitive behavior. However, activation of the vagus also stimulates microglia in the brain to produce cytokines via the central adrenergic system 

4.     A fourth pathway provides a slower immune-to-brain signaling mechanism based on volume transmission.  In this method of immune-to-brain communication, production of IL-1β by the brain first occurs in the choroid plexus and circumventricular organs—brain areas devoid of an intact blood-brain barrier. The cytokines then slowly diffuse throughout the brain by volume transmission, along the way activating microglia, neurons, and neural pathways that induce sickness behavior and inhibit cognition.


Can Flavonoids Reduce Neuroinflammation and Inhibit Cognitive Aging?

Flavonoids are naturally occurring polyphenolic compounds present in plants. The major sources of flavonoids in the human diet include fruits, vegetables, tea, wine, and cocoa.  Significant evidence has emerged to indicate that consuming a diet rich in flavonoids may inhibit or reverse cognitive aging

Flavonoids may improve cognition in the aged through a number of physiological mechanisms, including scavenging of reactive oxygen and nitrogen species and interactions with intracellular signaling pathways. Through these physiological mechanisms, flavonoids also impart an anti-inflammatory effect that may improve cognition. This seems likely for the flavone luteolin, which is most prominent in parsley, celery, and green peppers.
Whereas luteolin inhibits several transcription factors that mediate inflammatory genes (e.g., nuclear factor kappa B [NF-κB]and activator protein 1 [AP-1]), it is a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which induces the expression of genes encoding antioxidant enzymes. A recent study of old healthy mice found improved learning and memory and reduced expression of inflammatory genes in the hippocampus when luteolin was included in the diet. Thus, dietary luteolin may improve cognitive function in the aged by reducing brain microglial cell activity.
Hence, the flavonoid luteolin is a naturally occurring immune modulator that may be effective in reducing inflammatory microglia in the senescent brain.

Conclusion
In light of the recent evidence suggesting microglial cells become dysregulated due to aging and cause neuroinflammation, which can disrupt neural structure and function, it is an interesting prospect to think dietary flavonoids and other bioactives can be used to constrain microglia. But how can flavonoids impart this anti-inflammatory effect? Although in vitro studies clearly indicate that several flavonoids can act directly on microglial cells to restrict the inflammatory response, results from in vivo studies thus far do not prove that dietary flavonoids access the brain to interact with microglia in a meaningful way. This is a complicated question to dissect because flavonoids reduce inflammation in the periphery and microglia seem to act like an “immunostat,” detecting and responding to signals emerging from immune-to-brain signaling pathways. Thus, whether dietary flavonoids enter the brain and impart an anti-inflammatory effect on microglia is an interesting question but one that is more theoretical than practical because what is most important is how the immunostat is adjusted, whether that is via a direct or indirect route. However, because flavonoids are detectable in the brain they most likely affect microglia both directly and by dampening immune-to-brain signaling.



Interesting Natural Substances

In no particular order, these are several very interesting flavonoids/carotenoids.  In the lab, they all do some remarkable things.

In humans, they also do some interesting things; how helpful they might be in autism remains to be seen.

Being “natural” does not mean they are good for you and have no side-effects.

Some of the following are very widely used and so you can establish if there are issues with long term use.  It also makes them accessible.


Quercetin (found in many fruits, numerous interesting effects)


and two Quercetin-related flavonoids:-

Kaempferol (widely used in traditional medicine)

Myricetin (has good and bad effects)



Lycopene  (from tomatoes, potent anti-cancer, does not cross the BBB)

  
Luteolin(in many vegetables, like broccoli) 

Apigenin (from chamomile, stimulates neurogenesis, PAM of GABAA, block NDMA receptors, antagonist of opioid receptors …)


Tangeretin (from tangerines, does cross the BBB, has potent effects in vitro)


Nobiletin (from tangerines)

Hesperidin (from tangerines)


Naringin (from Grapefruit, contraindicated with many prescription drugs)


Epicatechin/Catechin  (the chocolate/cocoa flavonoids, do cross the BBB, well researched)








Tuesday, 4 November 2014

Why not Cocoa Flavanols for Autism?







  
Judging by my blog statistics, lots of people are interested in broccoli (Sulforaphane) to treat autism.  Thanks to the patents held by Johns Hopkins, you can expect to hear much more about Sulforaphane in the coming years.

Meanwhile, Columbia University and Mars, the chocolate people, have released a study showing that “flavanoids” in cocoa can do wonders for memory loss in older people.  In effect, they can restore memory in 60 years olds to where it was 20 or 30 years earlier.

If you take a step back and look at what is known by science about oxidative stress and antioxidants, all will become much clearer.


Oxidative Stress Pioneers

In an earlier post we met Paul Talalay, a German-American, who worked at Johns Hopkins.  He specializes in foods that protect you from cancer.  He is Mr Broccoli. 

It turns out that perhaps the real pioneer in this field is a 100% German, called Helmut Sies, who also studies foods that act as antioxidants and nutrients that provide protection from cancer.  We have his very detailed diagram below, that explains the relationship between many of the factors involved in oxidative stress.  I wish I had found it earlier.  I added the six outer boxes.

If you want to read clever studies about this subject, just include Helmut Sies in your search; for example “selenium Helmut Sies”.


Redox Pioneer: Professor Helmut Sies













On this graphic you will see GSH (Glutathione).  When you take NAC (N-acetylcysteine) you directly raise the level of GSH.  When eat broccoli you activate Nrf2, which is a Redox switch, just under the traffic light in the graphic.

When you eat certain flavonoids, like Cocoa, or carotenoids like lycopene (found in tomatoes), you again promote the anti-oxidative free radical scavenger effect.  Look in the blue boxes under diet.

Not on the diagram, we also have flavonolignans which are natural phenols composed of a part flavonoid and a part lignan. As pointed out in a comment in the last post by Seth Bittker, one interesting  flavonolignan is Silibinin, which has anti-oxidant and chemoprotective effects

Note the presence of (Coenzyme) Q10 in the yellow box.  This is part of the mitochondrial cocktail suggested by Dr Kelley from Johns Hopkins for regressive autism.  Q10 is depleted by statins.

Glutathione peroxidases, in the yellow box, are also very interesting.  These are selenium-containing enzymes.  GPx (x goes from 1 to 8)  catalyze the reduction of H2O2 and organic hydroperoxides to harmless products. This function helps to maintain membrane integrity and to reduce further oxidative damage to molecules such as lipids and lipoproteins with the associated increased risk of conditions such as atherosclerosis.  It appears GP1 may be defective in autism and this is contributes to increased oxidative stress.  This area has been well studied due to its impact on heart disease.  You appear to be able to counter the lack of GPx with yeast-bound selenium, other forms of selenium do not work, due to a lack of bioavailability. A post will appear just on Selenium.

There are several other potent (exogenous) antioxidants that we have come across:-

  • Alpha lipoic acid also known as ALA or Tioctic acid (found  in Dr Kelley’s cocktail)
  •   L-Carnosine (studied by Dr Chez )
  •  Vitamin C (suggested by many, including Dr Kelley)


Another day, another anti-oxidant

In human health, two well used anti-oxidant drugs are Alpha lipoic Acid (ALA,  also known as Tioctic acid) and N-acetyl cysteine (NAC).  They share many similar effects.

  •       Potent antioxidant
  •       Increase insulin sensitivity
  •       Improve memory in those with mild cognitive          impairment
  •       May lower blood pressure
  •       Improve behavior in autism

NAC is widely used to treat Chronic obstructive pulmonary disease (COPD) and ALA is used to treat diabetic neuropathy. Perhaps they could be interchanged

·        NAC has a chemoprotective effect
·        ALA has been shown to induce cell cycle arrest in  human breast cancers      cells

Back to Cocoa Flavanols and Mars

This flurry of activity was driven by a well publicized study done at Columbia University Medical Center (CUMC), using a high cocoa flavanol concentration drink provided by Mars.


   
In the CUMC study, 37 healthy volunteers, ages 50 to 69, were randomized to receive either a high-flavanol diet (900 mg of flavanols a day) or a low-flavanol diet (10 mg of flavanols a day) for three months. Brain imaging and memory tests were administered to each participant before and after the study. The brain imaging measured blood volume in the dentate gyrus, a measure of metabolism, and the memory test involved a 20-minute pattern-recognition exercise designed to evaluate a type of memory controlled by the dentate gyrus.
The high-flavanol group also performed significantly better on the memory test. “If a participant had the memory of a typical 60-year-old at the beginning of the study, after three months that person on average had the memory of a typical 30- or 40-year-old,” said Dr. Small. He cautioned, however, that the findings need to be replicated in a larger study—which he and his team plan to do.


This is very impressive.  But how do the other anti-oxidants compare?

Well, without funding from Mars, researchers only managed the money to test ALA and NAC on mice; but as you might expect, the result was similar.


Chronic administration of either LA or NAC improved cognition of 12-month-old SAMP8 mice in both the T-maze footshock avoidance paradigm and the lever press appetitive task without inducing non-specific effects on motor activity, motivation to avoid shock, or body weight. These effects probably occurred directly within the brain, as NAC crossed the blood-brain barrier and accumulated in the brain. Furthermore, treatment of 12-month-old SAMP8 mice with LA reversed all three indexes of oxidative stress. These results support the hypothesis that oxidative stress can lead to cognitive dysfunction and provide evidence for a therapeutic role for antioxidants.



Cocoa Flavanols are good for your heart

This is also good news, but it does seem that antioxidants are generally very good for your heart.

First cocoa.

In this study blood pressure, glucose, insulin and cholesterol were all markedly affected for the better by the cocoa as was cognitive function.

This is great;  but it is what Helmut Sies has been telling the world for many years.


Abstract—Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing _990 mg (high flavanols), _520 mg (intermediate flavanols), or _45 mg (low flavanols) of cocoa flavanols per day. Cognitive function was assessed by Mini Mental State Examination, Trail Making Test A and B, and verbal fluency test. At the end of the follow-up period, Mini Mental State Examination was similar in the 3 treatment groups (P_0.13). The time required to complete Trail Making Test A and Trail Making Test B was significantly (P_0.05) lower in subjects assigned to high flavanols (38.10_10.94 and 104.10_28.73 seconds, respectively) and intermediate flavanols (40.20_11.35 and 115.97_28.35 seconds, respectively) in comparison with those assigned to low flavanols (52.60_17.97 and 139.23_43.02 seconds, respectively). Similarly, verbal fluency test score was significantly (P_0.05) better in subjects assigned to high flavanols in comparison with those assigned to low flavanols (27.50_6.75 versus 22.30_8.09 words per 60 seconds). Insulin resistance, blood pressure, and lipid peroxidation also decreased among subjects in the high-flavanol and intermediate-flavanol groups. Changes of insulin resistance explained _40% of composite z score variability through the study period (partial r2_0.4013; P_0.0001). To the best of our knowledge, this is the first dietary intervention study demonstrating that the regular consumption of cocoa flavanols might be effective in improving cognitive function in elderly subjects with mild cognitive impairment. This effect appears mediated in part by an improvement in insulin sensitivity.







There are more cocoa studies:-




Cocoa Flavanols as a therapy for Autism

Based on the work of Helmut Sies and the trials funded by Mars, it is pretty obvious that 1,000mg of cocoa flavanols a day would very likely have a marked effect on someone with autism, assuming that is they were not already taking NAC, ALA, Carnosine, Broccoli, Sulforaphane or Selenium.  500 mg should also have an effect.


Choice of antioxidant

The question is what is the ultimate treatment for oxidative stress in autism?

I guess this will depend on exactly what type of autism you have (regressive or not), to what extent you have a mitochondrial dysfunction and whether you have any genetic dysfunction related to oxidative stress.

What works best in Billy, may be suboptimal in Charlie, but still much better than nothing at all.

It looks to me that NAC and ALA will likely be the most potent antioxidants.

If you live in the US, you can buy cocoa flavanols in standardized doses from Mars.  One capsule = 125mg of cocoa flavanols.   I have to add that I am far more inclined to believe Mars, than those supplement companies out there.  You can buy tablets saying they contain 50 mcg of Selenium, but what do they really contain? 

You can also buy “high flavanol” raw (non-alkalized) cocoa powder in big bags.  This lighter brown cocoa has lost far less of the flavonoids in the processing process.  In theory, a 5g teaspoon of the very best one will contain (on a good day) 415 mg of flavavols.

Mars are only supplying their CocoaVia products in North America, so if you want to try cocoa flavanols you have a few options:-

·        8.5 teaspoons of standard raw cocoa  (content will vary widely)
                or
·        1.2 teaspoons of “Chococru” upmarket raw cocoa

                or
·        4 capsules of CocoaVia from Mars  

Each of the above should give you 500mg of cocoa flavanols, which would look like a good starting point.  As with NAC, the studies show that the benefit increases the more you take, but the extra benefit drops off.

If somebody in the US tries CocoaVia, do let us know the result.

Not surprising, Mars tell us on the label that the product is not intended for children.  I do not suppose they ever thought of it being an autism therapy either.

I do like the idea of the redox switch, Nrf2, which Sulforaphane is known to activate.  I also like the idea of the enzyme GP1 that acts as catalyst in the oxidation/reduction process.

The science is around 20 years old and nobody has yet figured it all out;  they probably will not conclusively do so in the next 20 years either.


Food for thought!








Monday, 29 April 2013

Vitamin P may be good for you!

Now if the tittle makes sense to you, either you are a Prozac fan, or you were around in the 1940s and 50s when there actually was a vitamin P.

This blog is about autism, and in the US lots of such kids are prescribed the powerful antidepressant Prozac. We are more interested in the other vitamin P; these days they are called flavonoids.  This post will meander into other health problems but will return to ASD later on.

Flavonoids are found in plants and there are 5,000 of them.  In plants they have various functions, one of which is to provide colour (usually yellow, red and blue); in humans it is proposed that certain flavonoids may account for the beneficial properties of certain foods, ranging from chocolate to red wine.

There are many food supplements sold that contain flavonoids, three of the popular ones seem to be:-
 
·         Rutin
·         Quercetin
·         Luteolin

There is even a special mix made for autistic people called NeuroProtek.
 

In Vitro or in Vivo?

Some things work well in the test tube but not so well in us humans.  In vitro means in the glass and in vivo means in us living creatures.

Well, flavonoids have wonderful antioxidant properties, but it seems that is in only true in the test tube.  In vivo they are rather a flop.  Yet, if you read all the advertising for these flavonoid supplements, they rave about the antioxidant properties.

 
A great discussion of flavonoids is presented by the Linus Pauling Institute at Oregon State University. I have summarized much of it here and added the autism part.

 
Some flavonoids are good for you, but not as antioxidants

If flavonoids are not good antioxidants, why are they supposed to be good for you?  It seems that they have an entirely different role as signalling molecules.

Concentrations of flavonoids required to affect cell-signaling pathways are considerably lower than those required to affect cellular antioxidant capacity. Flavonoid metabolites may retain their ability to interact with cell-signaling proteins even if their antioxidant activity is diminished. Effective signal transduction requires proteins known as kinases that catalyse the phosphorylation (transferring a phosphate group (-PO4)) of target proteins at specific sites.

The results of numerous studies in cell culture suggest that flavonoids may affect chronic disease by selectively inhibiting kinases.

Cell growth and proliferation are also regulated by growth factors that initiate cell-signaling cascades by binding to specific receptors in cell membranes. Flavonoids may alter growth factor signaling by inhibiting receptor phosphorylation or blocking receptor binding by growth factors.

All this leads naturally to think that modulation of cell-signaling pathways by flavonoids could help prevent cancer.  Mechanisms proposed include:-

Stimulating phase II detoxification enzyme activity: Phase II detoxification enzymes catalyse that promote the excretion of potentially toxic or carcinogenic chemicals.

Preserving normal cell cycle regulation: Once a cell divides, it passes through a sequence of stages collectively known as the cell cycle before it divides again. Following DNA damage, the cell cycle can be transiently arrested at damage checkpoints, which allows for DNA repair or activation of pathways leading to cell death if the damage is irreparable. Defective cell cycle regulation may result in the propagation of mutations that contribute to the development of cancer.

Inhibiting proliferation and inducing apoptosis (cell death): Unlike normal cells, cancer cells proliferate rapidly and lose the ability to respond to cell death signals that initiate apoptosis.

Inhibiting tumor invasion and angiogenesis: Cancerous cells invade normal tissue aided by enzymes called matrix-metalloproteinases. To fuel their rapid growth, invasive tumors must develop new blood vessels by a process known as angiogenesis.

Decreasing inflammation: Inflammation can result in locally increased production of free radicals by inflammatory enzymes, as well as the release of inflammatory mediators that promote cell proliferation and angiogenesis (creation of new blood vessels) and inhibit apoptosis (beneficial cell death).

Modulation of cell-signaling pathways by flavonoids could help prevent cardiovascular disease by:

Decreasing inflammation: Atherosclerosis is now recognized as an inflammatory disease, and several measures of inflammation are associated with increased risk of heart attack.

Decreasing vascular cell adhesion molecule expression: One of the earliest events in the development of atherosclerosis is the recruitment of inflammatory white blood cells from the blood to the arterial wall.

Increasing endothelial nitric oxide synthase (eNOS) activity: eNOS is the enzyme that catalyzes the formation of nitric oxide by vascular endothelial cells. Nitric oxide is needed to maintain arterial relaxation. Impaired nitric oxide-dependent vasodilation is associated with increased risk of  cardiovascular disease.

Decreasing platelet aggregation: Platelet aggregation is one of the first steps in the formation of a blood clot that can occlude a coronary or cerebral artery, resulting in myocardial infarction or stroke, respectively. Inhibiting platelet aggregation is considered an important strategy in the primary and secondary prevention of cardiovascular disease.

 
Green tea and even red wine were supposed to have wonderful antioxidant properties; apparently this is not true after all.  They do seem to be good for you, but for completely different reasons.

People who consume larger amounts of flavonoids do seem to be healthier; but sadly that does not prove that eating flavonoids makes you healthy.  It might just be that a healthy diet just happens to be flavonoid-rich.

There is on-going research and multiple clinical trials into the possible benefits of flavonoids in these areas:-

Cardiovascular Disease

The results of some controlled clinical trials suggest that relatively high intakes of some flavonoid-rich foods and beverages, including black tea, purple grape juice, and cocoa (dark chocolate) has health benefits.

Cancer

The research is ongoing, it seems to show that those people with a diet rich in flavonoids have a lower risk of certain cancers; but it seems that tea consumption has no benefit here.

Neurodegenerative Disease

It is not clear to what extent flavonoids can cross into the brain thought the BBB (blood brain barrier).  Research is ongoing to see whether Parkinson’s disease, Alzheimer’s and dementia are correlated to flavonoids in the diet.  With 5,000 flavonoids this will take some time!

 
Flavonoid Content in Food
 
There are 5 principal types of flavonoids

1.    ANTHOCYANIDINS

Examples:- Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin

Supplements available include: Bilberry, elderberry, black currant, blueberry, red grape, and mixed berry extracts.  Don’t forget the red wine.

 
2.    FLAVONOLS

Examples:- Quercetin, Kaempferol, Myricetin, Isorhamnetin

The flavonol aglycone, quercetin, and its glycoside rutin are available as dietary supplements without a prescription in the U.S. Other names for rutin include rutinoside, quercetin-3-rutinoside, and sophorin. Citrus bioflavonoid supplements may also contain quercetin or rutin.

Flavonols are found in yellow onions, scallions, kale, broccoli, apples, berries and teas.

3.    FLAVONES

Examples:-  Luteolin, Apigenin

The peels of citrus fruits are rich in polymethoxylated flavones: tangeretin, nobiletin, and sinensetin. Although dietary intakes of these naturally occurring flavones are generally low, they are often present in citrus bioflavonoid supplements.

Flavones are found in parsley, thyme, celery, hot peppers, and chamomile

4.     LAVANONES

Examples:- Hesperetin, Naringenin, Eriodictyol

Citrus bioflavonoid supplements may contain glycosides of hesperetin (hesperidin), naringenin (naringin), and eriodictyol (eriocitrin). Hesperidin is also available in hesperidin-complex supplements

Lavanones are found in citrus fruits and juices, e.g., oranges, grapefruits, lemons


5.    FLAVANOLS 

A.    Monomers (Catechins)


B.    Dimers and Polymers:
examples:-  Theaflavins,  Thearubigins, Proanthocyanidins

Here is where to find them:-

Catechins: Teas (particularly green and white), chocolate, grapes, berries, apples
Theaflavins, Thearubigins: Teas (particularly black and oolong)
Proanthocyanidins: Chocolate, apples, berries, red grapes, red wine

 

USDA Database for the Flavonoid Content of Selected Foods

If you want to know which food contains how much of each flavonoid, just click on the link to go to a large database held by the US Department of Agriculture.
 

 
Another flurry of Patents

Not for the first time, I have noted that a flurry of patents have been filed in connection with autism.  This time it’s a couple of guys from the University of South Florida who see promise in the flavonoids :-  luteolin, diosmin, and diosmin's aglycone form, diosmetin.
 
The more prolific publisher is Theoharis Theoharides.  Here is an excerpt, from his patent:-
  
 






Theoharides is a big believer the benefit of luteolin.  Here is his main hypothesis Neuro-inflammation, blood-brain barrier, seizures and autism.


I like the fact that he is questioning the permeability of the BBB (blood brain barrier) in autism.  It seems entirely plausible and would account for many things.

  

Conclusion
 
Well I was already convinced that red wine was good for me.  Now I just have add the right vitamin P.

Time for a cup of tea, better make it chamomile (for the luteolin) and some dark chocolate.

Monty is still rather young for the red wine.  If he was French, though ….