A possibly interesting publication revealing 10-fold increase in inflammatory molecule in microvascular angina patients.

[JonathanH]

This post is rather long.

My “Google Scholar Alerts” have notified me of a possibly interesting abstract relating to the physiology of microvascular angina (MVA): ahajournals.org/doi/abs/10....

The abstract shows that the tested MVA patients had elevated levels of a number of inflammatory molecules, particularly one called IL-12. A table in the abstract shows a 10-fold increase in the IL-12 level; such an increase looks impressive to this layman. The abstract says: “We hypothesize that the significant increase in IL-12 levels observed in these patients may contribute to endothelial microvascular dysfunction as IL-12 is a known anti-angiogenic cytokine and shown to be linked to many autoimmune diseases. These results demonstrate that a TH-1 response is present in patients with microvascular disease.” A TH-1 response is a particular type of immune response. I have discovered that IL-12 induces a TH-1 response and therefore seems to be a key molecule in the process.

IL-12 is already implicated in cardiovascular diseases, according to the internet.

I thought that it would be interesting to investigate what can be done to reduce IL12. I have found that its production or action are suppressed by ACE inhibitors, statins (the experimental statin was atorvastatin) and vitamin D3, and by omega-3 fatty acids as well as various other dietary components mostly having plant sources. So, take your statin and ACE inhibitor, get the sun on your skin and continue eating the usual healthy diet that includes fish, whole grains, vegetables and berries. (I know that some argue against eating whole grains, in particular for those suffering from leaky guts, but I am concerned here only with reducing IL-12). All or most of the dietary components are available as supplements.

My list of inhibitors of the production or activity of IL-12 is as follows:

- ACE inhibitors captopril and lisinopril significantly suppress IL-12 production and the authors consider that other ACE inhibitors will do the same. (sciencedirect.com/science/a...

- atorvastatin suppresses IL-12 production, apparently in mice. Presumably other statins will do so. (nature.com/articles/nature0...

- 1,25-dihydroxy vitamin D3 (jlb.onlinelibrary.wiley.com.... This is the most active form of vitamin D and vitamin D3 is the type of vitamin D produced by the action of sunlight on skin. The same publication also refers to dexamethasone as an IL-12 suppressor.

- a particular conjugated linoleic acid (CLA) found in meat and dairy products. The molecule is cis-9, trans-11 isomer of conjugated linoleic acid (jimmunol.org/content/175/8/....

- butyrate (systematic name butanoate), a short chain fatty acid formed by digestion of fibre by gut bacteria. It is reported that “butyrate strongly inhibits the production of proinflammatory cytokines IL-12 and TNF-α by monocytes upon bacterial stimulation”. (fasebj.org/doi/abs/10.1096/.... It appears that butyrate production may be promoted by eating arabinoxylan-rich whole grains and brans from cereals such as wheat, rye and oats (

- oily fish fatty acids EPA and DHA reduce IL-12 production in mice and man (academic.oup.com/jid/articl...; journals.lww.com/jclinrheum...

- curcumin significantly inhibits IL-12 production in mice (ncbi.nlm.nih.gov/pmc/articl...

- sulforaphane that naturally occurs in cruciferous vegetables (broccoli, cabbage etc) impairs the expression of IL-12 in mice. The level of immunosuppressive activity did not excite the authors. (jimmunol.org/content/192/8/...

- quercetin, a flavonoid phytoestrogen that has profound anticancer and anti-inflammatory activities, blocks IL-12 signalling (ncbi.nlm.nih.gov/m/pubmed/1.... Quercetin is found in capers, red onions, berries, kale and apple skin, amongst other places.

- myricetin, a common plant-derived flavonoid that is very common in berries and vegetables, inhibits IL-12 production in mice (mdpi.com/2072-6643/8/2/90)

- parthenolide potently inhibits IL-12 production in a dose-dependent manner in mice (sciencedirect.com/science/a..., parthenolide being a compound found in the medicinal herb feverfew.

[Milkfairy Heart Star]

Hi Jonathan

Very interesting read. Thank you.

I will stick to my Mediterranean diet and eating oily fish, green leafy veg, berries, mixed seeds and yoghurt with a glass of red wine in moderation.

I will do my best to nurture my biome.

kcl.ac.uk/news/bacteria-inf...

kcl.ac.uk/news/low-diversit...

Keep taking the statins I have been prescribed.

I knew about ACE inhibitors but Candesartin crashed my BP so they are off the list.

Not everyone with non obstructive coronary artery disease has microvascular dysfunction. For some it is a vasomotion disorder of the blood vessels themselves causing microvascular and coronary vasospasms.

[MichaelJH Heart Star]

Whilst I do not have MVA the indications therein are that my statin (Atorvastatin) and ACE inhibitor (lisinopril) are beneficial. I did err the other day though when I had the Ace breakfast (but no chips). 😐

[Ianc2]

Veg, berries, feverfew, apples, broccoli, porridge, oily fish, all good stuff..

Ace inhibitors - rampiril? and some solid evidence that taking a statin works.

Interesting post full of information but has anyone replicated this in humans?

[JonathanH in reply to Ianc2]

I hadn't looked until your question prompted me to investigate curcumin in humans, and it "decreases IL-12-induced STAT4 phosphorylation, IFN-γ production, and IL-12 Rβ1 and β2 expression" in human T cells. I infer that the decreases in STAT4 phosphorylation and IFN production are anti-inflammatory. You can read this at ncbi.nlm.nih.gov/pmc/articl.... If you follow through one or two of the references, you will find that the authors of the paper seem to accept without question that observations made in mice apply in man, which is surely wrong of them.

I have not in a quick search located such a paper relating to quercetin.

[CPL593H]

That was a good read, thank you

[CretanBob]

I posted this in another thread, but I am currently having investigations into the possible cause of an unexplained event last year, which may be put down to an arthritic condition linked to long term but mild psoriasis condition. It is well know that the inflammation can cause blockages.

As for statins, my cholesterol continues to rise (with my upper body joint pain) being off statins and on them. There are a couple of more added dietary considerations in your piece - thank you.

[dunestar]

Thanks Jonathan, very interesting information. On the gut biome side of things a friend was visiting at the weekend who has a degree in nutrition and keeps up to date with the latest research. He mentioned a product from a US supplement company (I do know the name but not sure about whether I can mention it on the forum) which has developed a gut biome product specifically for good heart health. He is taking it and says he'll report back on how he feels.

[JonathanH in reply to dunestar]

That would be most interesting. Please do say how your friend gets on. I don't see any harm in your naming the supplement, especially as you're not recommending it but only informing us of its existence. Your readers can then do their research and decide whether to buy it.

[dunestar in reply to JonathanH]

Hi Jonathan. The product is called Florassist Heart Health by Life Extension Europe. It contains the probiotic Lactobacillus reuteri 30242.

[Milkfairy Heart Star]

Hi Jonathan you might be interested in this article?

theguardian.com/lifeandstyl...

The BBC 'Trust me I am a doctor' programme discussed gut flora about a year ago.

bbc.co.uk/programmes/articl...