You might be wondering the relevance of arthritis to
an autism blog. Rheumatoid arthritis is an
inflammatory condition in which the body's own immune system
starts to attack body tissues. It is
often co-morbid with inflammatory bowel disease
(including Crohn's disease and ulcerative colitis). IBD is comorbid with autism. The study below shows how many autoimmune
diseases, including arthritis are connected with autism.
This gives yet more reason to look into PEA for autism, but not to forget Luteolin.
Applications of Quercetin
Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation.
Inflammation
Several laboratory studies show quercetin may have anti-inflammatory properties, and it is being investigated for a wide range of potential health benefits.
Quercetin has been reported to be of use in alleviating symptoms of pollinosis. An enzymatically modified derivative was found to alleviate ocular but not nasal symptoms of pollinosis.
Studies done in test tubes have shown quercetin may prevent immune cells from releasing histamines which might influence symptoms of allergies.
A study with rats showed that quercetin effectively reduced immediate-release niacin (vitamin B3) flush, in part by means of reducing prostaglandin D2 production. A pilot clinical study of four humans gave preliminary data supporting this.
Health effects of Rutin
While a body of evidence for the effects of rutin and quercetin is available in mice, rats, hamsters, and rabbits, as well as in vitro studies, no clinical studies directly demonstrate significant, positive effects of rutin as dietary supplement in humans.
Vox Populi (from Amazon.com reviews)
RESULTS: A total of 3325
children were diagnosed with ASDs, of which 1089 had an infantile autism
diagnosis. Increased risk of ASDs was observed for children with a maternal
history of rheumatoid arthritis and celiac disease. Also, increased risk of
infantile autism was observed for children with a family history of type 1
diabetes.
CONCLUSIONS: Associations regarding
family history of type 1 diabetes and infantile autism and maternal history of
rheumatoid arthritis and ASDs were confirmed from previous studies. A
significant association between maternal history of celiac disease and ASDs was
observed for the first time. The observed associations between familial
autoimmunity and ASDs/infantile autism are probably attributable to a
combination of a common genetic background and a possible prenatal antibody
exposure or alteration in fetal environment during pregnancy.
Note that in an earlier post on the vagus nerve, we saw
how an implanted vagus nerve stimulator could reduce the inflammation in
arthritis. This is being developed as an alternative to the extremely expensive new drugs for arthritis that target IL-6 and TNF.
In earlier posts on Mast Cells we heard all about Dr
Theoharides from Tufts University who is big on using naturally occurring flavonoids
to stabilize mast cells and so treat all kinds of allergic reactions as in
mastocytosis and in some types of autism.
See below for a reminder of the roll mast cells play in allergies:-
Source: Wikipedia
Luteolin is Theoharides’ favourite flavonoid because it is the most the most lipophilic and therefore more likely
to enter the brain. Mast cells are all over the
body, including the brain. In autism, he
clearly is focused on the mast cells in the brain, but perhaps the mast cells
elsewhere are equally problematic.
Indeed, perhaps the mast cells outside the brain are far more important,
just because there are far more of them and the inflammatory mediators released
by them will travel throughout the entire body.
The other two flavonoids know to effect mast cells and
inflammation are Rutin and Quercetin.
Arthritis
Luteolin and Palmitoylethanolamide
I was quite surprised to find that research had been
carried out on the anti-inflammatory effect of both Luteolin and
Palmitoylethanolamide (PEA). PEA is the
substance I have been researching recently, it is not a flavonoid, but it is
naturally occurring within the body and has some very interesting properties.
One of the inflammatory markers that is raised in
autism is called IL-6. The research was
on arthritis in mice, but it did measure the effect of Luteolin and PEA on
IL-6. The result was interesting:-
PEA had the greater effect, but in combination with
Luteolin the result improved further.
This gives yet more reason to look into PEA for autism, but not to forget Luteolin.
The problem
with Luteolin and Theoharides’ formulation called Neuroprotek is that it is
really expensive in the suggested dosage.
What about Quercetin?
Quercetin is
relatively cheap.
Unfortunately
there is no direct comparison of Luteolin vs Quercetin in arthritis, but there
is plenty of research showing that Quercetin is highly beneficial in arthritis.
Abstract
Pentahydroxyflavone
dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants
and has been suggested to modulate inflammatory responses in various models. In
the present study, we investigated in vivo effects of oral or intra-cutaneous
QU in chronic rat adjuvant-induced arthritis (AA). Growth delay and arthritic
scores were evaluated daily after AA induction in Lewis rats. Oral
administration of QU (5 x 160 mg/kg) to arthritic rats resulted in a clear
decrease of clinical signs compared to untreated controls. Intra-cutaneous
injections of lower doses (5 x 60 mg/kg) of QU gave similar anti-arthritic
effects, while 5 x 30 mg/kg concentrations were inefficient in this respect.
Finally, injection of relatively low QU doses (5 x 30 mg/kg) prior to AA
induction significantly reduced arthritis signs. As QU was suggested to inhibit
macrophage-derived cytokines and nitric oxide (NO), we then analyzed macrophage
response ex vivo. Anti-arthritic effects of QU correlated with significant
decrease of inflammatory mediators produced by peritoneal macrophages, ex vivo
and in vitro. These data
indicate that QU is a potential anti-inflammatory therapeutic and preventive
agent targeting the inflammatory response of macrophages.
Here is a
great paper summarizing the many and varied benefits of quercetin:-
An
interesting point with all flavonoids is their bioavailability. This means what proportion that you eat is
actually absorbed.
Quercetin is
present in apples, but the largest amount is in the peel and is highest in red
apples. Quercetin is found is lesser amounts in red
wine, but it appears the bioavailability is much higher because of the alcohol. So grape juice would not help much. Applications of Quercetin
Asthma
Quercetin is an effective bronchodilator and helps reduce the release of histamine and other allergic or inflammatory chemicals in the body.Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation.
Cancer
Laboratory studies have investigated Quercetin's potential for use in anti-cancer applications. The American Cancer Society says while quercetin "has been promoted as being effective against a wide variety of diseases, including cancer," and "some early lab results appear promising, as of yet there is no reliable clinical evidence that quercetin can prevent or treat cancer in humans."Eczema
Serum IgE levels are highly elevated in eczema patients, and virtually all eczema patients are positive for allergy testing. Excessive histamine release can be minimized by the use of antioxidants. Quercetin has been shown to be effective in reducing IgE levels in rodent models.
Inflammation
Several laboratory studies show quercetin may have anti-inflammatory properties, and it is being investigated for a wide range of potential health benefits. Quercetin has been reported to be of use in alleviating symptoms of pollinosis. An enzymatically modified derivative was found to alleviate ocular but not nasal symptoms of pollinosis.
Studies done in test tubes have shown quercetin may prevent immune cells from releasing histamines which might influence symptoms of allergies.
A study with rats showed that quercetin effectively reduced immediate-release niacin (vitamin B3) flush, in part by means of reducing prostaglandin D2 production. A pilot clinical study of four humans gave preliminary data supporting this.
Fibromyalgia
Quercetin may be effective in the treatment of fibromyalgia because of its potential anti-inflammatory or mast cell inhibitory properties shown in laboratory studiesMonoamine-oxidase inhibitor
Possibly an active component of heather, quercetin was suspected from a bioassay test on crude extracts to selectively inhibit monoamine oxidase, possibly indicating pharmacological properties.Prostatitis
Quercetin has been found to provide significant symptomatic improvement in most men with chronic prostatitis, a condition also known as male chronic pelvic pain syndrome.
Luteolin
Luteolin is known to stabilize mast cells. It has been studied in several preliminary in
vitro scientific investigations. Proposed activities include antioxidant
activity (i.e. scavenging of free radicals), promotion of carbohydrate
metabolism, and immune system modulation. Other in vitro studies suggest
luteolin has anti-inflammatory activity, and that it acts as a monoamine transporter activator, a phosphodiesterase inhibitor, and an
interleukin 6 inhibitor. In vivo
studies show luteolin affects xylazine/ketamine-induced
anesthesia in mice. In vitro and in vivo experiments also suggest
luteolin may inhibit the development of skin cancer.
In autism
the ability to stabilize mast cells and inhibit IL-6 is very useful.
Luteolin, a flavonoid found in
high concentrations in celery and green pepper, has been shown to reduce
production of proinflammatory mediators in LPS-stimulated macrophages,
fibroblasts, and intestinal epithelial cells. Because excessive production of
proinflammatory cytokines by activated brain microglia can cause behavioral
pathology and neurodegeneration, we sought to determine whether luteolin also
regulates microglial cell production of a prototypic inflammatory cytokine,
IL-6. Pretreatment of primary murine microlgia and BV-2 microglial cells with
luteolin inhibited LPS-stimulated IL-6 production at both the mRNA and protein
levels. To determine how luteolin inhibited IL-6 production in microglia, EMSAs
were performed to establish the effects of luteolin on LPS-induced binding of
transcription factors to the NF-κB and activator protein-1 (AP-1) sites on the
IL-6 promoter. Whereas luteolin had no effect on the LPS-induced increase in
NF-κB DNA binding activity, it markedly reduced AP-1 transcription factor
binding activity. Consistent with this finding, luteolin did not inhibit
LPS-induced degradation of IκB-α but inhibited JNK phosphorylation. To
determine whether luteolin might have similar effects in vivo, mice were provided
drinking water supplemented with luteolin for 21 days and then they were
injected i.p. with LPS. Luteolin consumption reduced LPS-induced IL-6 in plasma
4 h after injection. Furthermore, luteolin decreased the induction of IL-6 mRNA
by LPS in hippocampus but not in the cortex or cerebellum. Taken together, these data
suggest luteolin inhibits LPS-induced IL-6 production in the brain by
inhibiting the JNK signaling pathway and activation of AP-1 in microglia. Thus,
luteolin may be useful for mitigating neuroinflammation.
Health effects of Rutin
While a body of evidence for the effects of rutin and quercetin is available in mice, rats, hamsters, and rabbits, as well as in vitro studies, no clinical studies directly demonstrate significant, positive effects of rutin as dietary supplement in humans.
- Rutin inhibits platelet
aggregation, as well as decreases capillary permeability, making the blood
thinner and improving circulation.]
- Rutin shows anti-inflammatory
activity in some animal and in vitro models]
- Rutin inhibits aldose reductase activity.
- Recent studies show
rutin could help prevent blood clots, so could be used to treat patients
at risk of heart attacks and strokes.
- Some evidence also
shows rutin can be used to treat hemorrhoids, varicosis, and microangiopathy.
- Rutin increases
thyroid iodide uptake in rats without raising serum T3 or T4.
- Rutin is also an antioxidant, compared to quercetin, acacetin, morin, hispidulin, hesperidin, and naringin, it was found to be the strongest. However, in other trials, the effects of rutin were lower or negligible compared to those of quercetin.
Vox Populi (from Amazon.com reviews)
Rutin
Few comments
- “This works wonders for hemorrhoids”
Quercetin
Hundreds of positive comments for: Nasal allergy, eczema, sinusitis,
prostatitis, joint pain etc.
“Lifesaver
for allergies”
“This really helps and works like Sudafed”
Luteolin / Neuroprotek
(main ingredient is Luteolin)
Few comments mainly: mastocytosis, allergies, eczema, autism
Works for some people with autism and not for
others:
“My son with autism stopped his aggressive
behaviour in a day”
“Works for my
fibromyalgia”
Conclusion
I do have a
couple of jars of Neuroprotek, which I was going to try on Monty, aged 10 with
ASD, when the pollen season returns in the summer. Using it all year round would not be cheap
and might have little effect. I find
Quercetin very interesting and worthy of investigation; but PEA remains my current
favourite.
It does come
down to the question of which mast cells de-granulating cause the problem in
autism. In some people it could be the
ones in their digestive tract and in others the ones in their eyes and
nose. The ones in the brain may or may
not be relevant; these are the ones Theoharides seems to focus on.
PEA,
Quercetin and Luteolin seem to have many benefits unrelated to mast cells. Since they cannot be patented, there is no
incentive for Big Pharma to invest in developing their potential. So even if they did had some remarkable
property, like in cancer therapy, we would likely never find out.
If I was a mouse
with arthritis, I would add PEA and Quercetin (or Luteolin) to my weekly
shop. Anyone who is a big user of H1
antihistamines should find Quercetin helpful.
Hello,
ReplyDeleteHave you tried Neuroprotek on your son? Did you get good results? Also, what't your take on this : http://scienceblogs.com/insolence/2013/07/30/autismfreebrain-selling-supplements-to-cure-autism/
I did try it and its "creator", Theoharides, is without doubt a clever guy. Verapamil is 100x better and works from the first pill. Neuroprotek is very expensive, you need a lot of it, and Theoharides says it takes months to show an effect. I do use Quercetin, which also has an immediate effect.
ReplyDeleteI did write to tell Theoharides about Verapamil - but no reply.
There is a vast amount of nonsense written about autism on the internet, it is much better to ignore it and just follow the science. Use Google scholar to find the science.
Cromolyn Sodium, and even H1 antihistamines (some sold OTC) have an almost immediate effect on mast cells; but Verapamil is by far the most effective in my son.
It is said that luteolin supplements have wide applications and play an important role in our lives. From here: www.nfextracts.com/luteolin-supplements. Generally speaking, they are useful for the treatment of some diseases.
ReplyDeleteHow do you give NeuroProtek? I bought the capsules but my son won't swallow pills. Do you let M chew them? Or do you open and empty them? We just made a mess of it this morning- HELP
ReplyDeleteYou can open them and mix them in something like apple sauce. If you use omega 3 oil, you could mix it in that. You can also squeeze out the contents onto a small piece of toast.
DeleteI've read some articles recently where researchers caution against giving concentrated flavonoids (like those found in supplements) to kids as they can affect the endocrine system, and potentially cause harm. But we also know how valuable flavonoids are as mast cell blockers. What do you think of the risk/benefit approach to giving flavonoid supplements?
ReplyDeleteI tried Quercetin myself as well as giving it to my son. It did great things for me, but then after a while had less good effects. I looked into the science and found research showing how it could be both anti-oxidant and also pro-oxidant. Many natural substances can affect hormones, even eating a few grapefruit a day, as one reader told me, can increase progesterone levels. In my case I got tendonitis in my ankle, which is a frequent side effect of steroid use. I stopped the Quercetin and it went away. However the occasional use for sinusitis seems to be trouble free and highly effective in other family members. Summertime use in small doses (half a capsule) does seem to help my son with ASD. I do not give it year round.
DeleteI have been very interested in your writing on mast cells, as my daughter has randomly had a couple of mild allergic reactions (not seasonal) and suffers from chronic constipation which I have read could be a sign of food allergies/sensitivities. However, my daughter also suffers from frequent illnesses and is generally sick a lot (which I have also read is common with autism). Do you have an opinion about whether the use of mast cell stabilizers like those described in this article would interfere with the body's ability to respond to true infections? While I believe some type of immune process might be involved in my daughter's autism symptoms, I worry about using treatments that might further compromise her immune system's ability to keep her body healthy.
ReplyDeleteSome immunomodulating therapies used in autism, like steroids would indeed reduce the body's ability to react to harmful threats. I do not believe this occurs using mast cell stabilizers. My son with ASD is healthier than his brother. A wide mixture of flavonoids, as found in a diet full of berries and fruits, or in a few drops of propolis does have an effect on general health.
DeleteI would see no harm in trying these interventions.
Hi I have PEA which I aquired to help with cannabis withdrawal(I know, I know, it doesn't exist ;) ) Anyways my son also has autism and I have tried the pea so many times due to all of the impressive research, and it literally makes him go apeshit. Verbal stimming goes through the roof, and his behavior becomes intolerable. So we have never made it through the adjustment period. It is not micronized, so I was wondering if this is the problem. I notice it can cause me intestinal issues when I take too much on an empty stomach. I am wondering how PEA is working out for you. It has some of the most promising evidence I have seen popping up of any ASD supplement, so it kills me not to use it. If it is working well for you, at what dosage does it? Was there any issues like mine? an adjustment period? For what its worth same reaction to luteolin, and I see they state increased irritability is a transient side effect of luteolin in 1/2 of the subjects for 1-8 weeks. How does anyone tolerate 8 weeks of increased irritability and in my case vocal stimming...
ReplyDeleteMark, we tried PEA and it had no effect at all.
DeleteIf it has a negative effect, probably best not to use it.
Has anyone found a supplement that is a good source of luteolin (beyond Neuroprotek)?
ReplyDeleteI've been using a new product called MIRICA that contains both PEA and luteolin for neuropathy. It works so well for reducing pain and anxiety.
ReplyDeletePeanuts and egg yolks (both food favorites of mine) contain PEA... I wonder why I never made the link... PEA being a GPR55 agonist and can modulate mesolimbic dopamine activity.
ReplyDeleteBefore I start buying PEA, Im struggling to find information regarding the amount of PEA present in peanuts/peanutbutter. It also seems present in soy lecithin (decent results in the past Ive had with this). Does anyone know how much PEA is present naturall in peanuts?