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)

examples:- Catechin, Epicatechin, Epigallocatechin Epicatechin gallate, Epigallocatechin gallate

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.

 

USDA Database for the Flavonoid Content of Selected Foods

 

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.

A more recent paper, again about luteolin is:- Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release,which is inhibited by luteolin

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 ….