![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by Trotter on December 11, 2012, at 2:55:57
Recently I have been reading how inflammation and pro-inflammatory cytokines can cause depression. I am looking at way to reduce PICs. I have read that reducing omega-6 fats while increasing omega-3s is a good idea. Turmeric/curcumin and ginger may also help. Anyone got any other ideas?
Posted by SLS on December 11, 2012, at 7:22:54
In reply to How do I lower pro-inflammatory cytokines?, posted by Trotter on December 11, 2012, at 2:55:57
> Recently I have been reading how inflammation and pro-inflammatory cytokines can cause depression. I am looking at way to reduce PICs. I have read that reducing omega-6 fats while increasing omega-3s is a good idea. Turmeric/curcumin and ginger may also help. Anyone got any other ideas?
Check out minocycline. Minocycline is used as an antibiotic, but it has other several properties, some of which reduce inflammation in the brain.
http://www.ncbi.nlm.nih.gov/pubmed/22486246
200 mg/day is often chosen in clinical studies.
http://clinicaltrials.gov/show/NCT01403662
http://clinicaltrials.gov/show/NCT01514422
"Several lines of evidence implicate the inflammatory system as consequential and causative to mood disorder. Bipolar disorder is marked by alterations in inflammatory cytokines (e.g. TNF-alpha, IL-6). Moreover, pro-inflammatory activation in both healthy and medically ill individuals is associated with disturbances in affective, cognitive, and somatic function.
The clinical use of cytokine-based therapy has been demonstrated to induce and/or intensify affective symptomatology in non-psychiatric medical patients. Conventional pharmacological treatments (e.g. lithium) for bipolar disorder affects the production of pro-inflammatory cytokines as well as their gene expression. The encompassing aim of the study herein is to develop a novel treatment for bipolar depression based on a model of disease pathophysiology. Minocycline is a semisynthetic second-generation tetracycline, which exerts anti-inflammatory effects that are distinct from its antimicrobial properties.
Minocycline is a potent inhibitor of microglial activation and decreases expression of pro-inflammatory cytokines, chemokines and their receptors and suppresses the activity of matrix metalloproteinases. Minocycline has been shown to exert antidepressant-like properties in preclinical studies. Rats treated with minocycline monotherapy as well as combination treatment with an antidepressant (desipramine) exhibited significantly improved performance on the forced swim test. Adjunctive minocycline has been shown to be efficacious for the treatment of schizophrenia in a double-blind, randomized, placebo-controlled study. Subjects receiving minocycline exhibited a significant improvement in negative symptoms as well as global improvement as measured with the Clinical Global Impression (CGI). Significant improvement was also noted on measures of executive function, including executive function composite score, spatial recognition memory, cognitive planning, and intradimensional/extradimensional set shifting."
- Scott
Posted by Phillipa on December 11, 2012, at 9:56:17
In reply to Re: How do I lower pro-inflammatory cytokines? » Trotter, posted by SLS on December 11, 2012, at 7:22:54
When thinking of using the minocycline I have it seems that it's only effective in either bipolar or schizophrenic type illnesses and not depression or anxiety. I do know that the one time took motrin 800mg a day for one day I felt better the next day. It of course could have been a coinsidence. Phillipa
Posted by SLS on December 11, 2012, at 10:30:01
In reply to Re: How do I lower pro-inflammatory cytokines? » SLS, posted by Phillipa on December 11, 2012, at 9:56:17
> When thinking of using the minocycline I have it seems that it's only effective in either bipolar or schizophrenic type illnesses and not depression or anxiety.
I don't know what you base your opinion on regarding minocycline and depression, but it is in conflict with the treatment suggestions offered by the Harvard/Mass General psychiatric department. This is according to someone I know who is currently responding to minocycline as a result of this suggestion. I don't know how they came to their opinion, though. There is now enough interest in minocycline such that it is being studied for unipolar depression. It is early yet, so I can't present any citations reflecting completed clinical trials. It is quite possible that you are right in your impressions of the antidepressant activity of minocycline, but it is unlikely that it would hurt for you to try. The first few days of treatment can produce anxiety, but this appears to disappear quickly.
- Scott
Posted by Hugh on December 11, 2012, at 14:39:02
In reply to How do I lower pro-inflammatory cytokines?, posted by Trotter on December 11, 2012, at 2:55:57
Probiotics can reduce cytokine levels. I've found that kefir (fermented milk) has mood-boosting properties. Kefir is a good source of probiotics. Here's some info on using probiotics for depression:
Posted by Trotter on December 11, 2012, at 16:16:26
In reply to Re: How do I lower pro-inflammatory cytokines?, posted by Hugh on December 11, 2012, at 14:39:02
Thanks for that link. Lactobacillus GG looks promising.
Posted by Trotter on December 11, 2012, at 16:22:18
In reply to Re: How do I lower pro-inflammatory cytokines? » Trotter, posted by SLS on December 11, 2012, at 7:22:54
Minocycline looks very interesting. I am looking further into it.
This may be a silly question, but why don't NSAIDs work as antidepressants by inhibiting PICs?
Do you think curcumin might work better than NSAIDs to reduce PIC and depression?
Posted by Trotter on December 11, 2012, at 17:16:52
In reply to How do I lower pro-inflammatory cytokines?, posted by Trotter on December 11, 2012, at 2:55:57
Apparently NSAIDs can reduce the effectiveness of antidepressants, particularly SSRIs, supposedly because they suppress pro-inflammatory cytokines. This is a worry. I was looking at ways to reduce cytokine production, but this might be counterproductive if taking ADs. Bugger!
http://blogs.psychcentral.com/bipolar/2011/07/nsaid-ssri-antidepressant/
Posted by joe schmoe on December 11, 2012, at 17:19:29
In reply to Re: How do I lower pro-inflammatory cytokines? » SLS, posted by Trotter on December 11, 2012, at 16:22:18
Reducing systemic inflammation is kind of a large subject but one thing you might want to look into is the role of polyunsaturated fats. From what I have read, the mainstream idea that saturated (animal, and coconut) fats are bad for you is completely backwards. It is actually polyunsaturated fats, which primarily come from unnatural sources like seed oils (so-called "vegetable" oils) which are bad. Unlike saturated fats, which are quite stable, polyunsaturated fats are very easily oxidized either during cooking or in the body. If you eat a lot of polyunsaturated fats, the composition of your LDL reflects this, and you end up with easily oxidized (or already oxidized, especially if high temperature cooking like deep frying was used) small-particle-size LDL, which tends to get between endothelium cells in arteries and cause an inflammation reaction. This reaction attracts macrophages to gobble up the oxidized LDL and become "foam cells", and T cells which secrete....cytokines.
Here's an article on the role of oxidized LDL in coronary diseases:
Atherosclerosis: Evolving Vascular Biology and Clinical Implications: Inflammation in Atherosclerosis and Implications for Therapy
http://circ.ahajournals.org/content/109/23_suppl_1/III-20.full
Like I said it's a large subject and it's mainly the pioneers in research who seem to know what is going on. Everytime I read a mainstream article or food label where the message is to avoid saturated fat and eat more "vegetable oils" I groan, thinking of all those poor people out there whose arteries are clogging up with atherosclerosis as I type this, due to all their consumption of canola oil, soybean oil, peanut oil, fried foods etc.
Posted by Trotter on December 11, 2012, at 18:25:50
In reply to Re: How do I lower pro-inflammatory cytokines?, posted by joe schmoe on December 11, 2012, at 17:19:29
While I agree polyunsaturated fats may be bad for you, I think saturated fats associated with red meat are high in omega-6 fatty acids which are supposed to increase pro-inflammatory cytokines. Conversely, omega-3s are meant to reduce inflammation.
Posted by joe schmoe on December 11, 2012, at 19:20:30
In reply to Re: How do I lower pro-inflammatory cytokines? » joe schmoe, posted by Trotter on December 11, 2012, at 18:25:50
> While I agree polyunsaturated fats may be bad for you, I think saturated fats associated with red meat are high in omega-6 fatty acids which are supposed to increase pro-inflammatory cytokines. Conversely, omega-3s are meant to reduce inflammation.
Hi,
Actually omega-6 and omega-3 are both polyunsaurated fatty acids. Saturated fats are not "omega" anything. The omega notation is to show how far from the end of the molecule (in carbons) the last carbon single bond is. Saturated fats have only carbon double bonds, which is why they are highly resistant to oxidation, and are used by the body as energy storage and fuel. Yes, if you eat carbs, they are quickly converted into and stored as saturated fat.
If you want to cut out omega-6's, cut out vegetable oils and processed foods using them.
Posted by SLS on December 11, 2012, at 19:26:10
In reply to Re: How do I lower pro-inflammatory cytokines?, posted by joe schmoe on December 11, 2012, at 17:19:29
Very interesting.
Thanks.
- Scott> Reducing systemic inflammation is kind of a large subject but one thing you might want to look into is the role of polyunsaturated fats. From what I have read, the mainstream idea that saturated (animal, and coconut) fats are bad for you is completely backwards. It is actually polyunsaturated fats, which primarily come from unnatural sources like seed oils (so-called "vegetable" oils) which are bad. Unlike saturated fats, which are quite stable, polyunsaturated fats are very easily oxidized either during cooking or in the body. If you eat a lot of polyunsaturated fats, the composition of your LDL reflects this, and you end up with easily oxidized (or already oxidized, especially if high temperature cooking like deep frying was used) small-particle-size LDL, which tends to get between endothelium cells in arteries and cause an inflammation reaction. This reaction attracts macrophages to gobble up the oxidized LDL and become "foam cells", and T cells which secrete....cytokines.
>
> Here's an article on the role of oxidized LDL in coronary diseases:
>
> Atherosclerosis: Evolving Vascular Biology and Clinical Implications: Inflammation in Atherosclerosis and Implications for Therapy
>
> http://circ.ahajournals.org/content/109/23_suppl_1/III-20.full
>
> Like I said it's a large subject and it's mainly the pioneers in research who seem to know what is going on. Everytime I read a mainstream article or food label where the message is to avoid saturated fat and eat more "vegetable oils" I groan, thinking of all those poor people out there whose arteries are clogging up with atherosclerosis as I type this, due to all their consumption of canola oil, soybean oil, peanut oil, fried foods etc.
Posted by Trotter on December 11, 2012, at 23:46:52
In reply to Re: How do I lower pro-inflammatory cytokines? » Trotter, posted by joe schmoe on December 11, 2012, at 19:20:30
> > While I agree polyunsaturated fats may be bad for you, I think saturated fats associated with red meat are high in omega-6 fatty acids which are supposed to increase pro-inflammatory cytokines. Conversely, omega-3s are meant to reduce inflammation.
>
> Hi,
>
> Actually omega-6 and omega-3 are both polyunsaurated fatty acids. Saturated fats are not "omega" anything. The omega notation is to show how far from the end of the molecule (in carbons) the last carbon single bond is. Saturated fats have only carbon double bonds, which is why they are highly resistant to oxidation, and are used by the body as energy storage and fuel. Yes, if you eat carbs, they are quickly converted into and stored as saturated fat.
>
> If you want to cut out omega-6's, cut out vegetable oils and processed foods using them.Right you are that both omega-6 and omega-3 fatty acids are polyunsaturated oils.
I don't consume much in the way of omega-6 from vegetable oils. I cook with virgin olive oil (at relatively low temperature). I think my main source of omega-6 is from red meat and cheese.
After doing some more research today I now believe that supplementation with EPA (but not DHA) omega-3 oil is beneficial because it reduces inflammation. EPA also seems to be the omega-3 that is effective in reducing depression, possibly through its antiinflammatory action.
Posted by joe schmoe on December 12, 2012, at 6:58:51
In reply to Re: How do I lower pro-inflammatory cytokines? » joe schmoe, posted by Trotter on December 11, 2012, at 23:46:52
> Right you are that both omega-6 and omega-3 fatty acids are polyunsaturated oils.
>
> I don't consume much in the way of omega-6 from vegetable oils. I cook with virgin olive oil (at relatively low temperature). I think my main source of omega-6 is from red meat and cheese.
>
> After doing some more research today I now believe that supplementation with EPA (but not DHA) omega-3 oil is beneficial because it reduces inflammation. EPA also seems to be the omega-3 that is effective in reducing depression, possibly through its antiinflammatory action.
Olive oil is not a seed oil and is high in monounsaturated fat so it is certainly a better choice to cook with than seed oils like corn oil or canola oil. It still vulnerable to some oxidation from heat however so I only use it on salads. Personally I prefer to cook with coconut oil since it is almost entirely saturated fat and very resistant to oxidation.I take fish oil every day, to rebalance my omega 3's and 6's since they compete for the same enzymes to make different inflammatory chemicals, but have never noticed any effect on my mood from it. The impression I get from lipid experts is to reduce omega 6 intake by cutting out processed foods/seed oils as much as possible, and eat more fish/supplement with fish oil, but not to overdo it, since you don't want to be eating a lot of polyunsaturated fats of any kind. It's more important to reduce omega 6 consumption. There is a magic level of calorie intake from omega 6, I think it's 4%, above this bad things seem to happen regardless of omega 3 intake.
While I'm at it let me link you to a couple posts at a nutrition researcher's excellent blog. I highly recommend reading as much of this blog as you can. There is a lot of great information there.
http://wholehealthsource.blogspot.com/2009/05/eicosanoids-and-ischemic-heart-diseas.html
http://wholehealthsource.blogspot.com/2009/05/for-those-not-scientifically-inclined.html
Incidentally you can also get omega 3's (and vitamin K2) from more naturally raised food - eggs from free range chickens (they eat insects, not just corn), butter and cheese from grass fed cows, beef from grass fed cattle. Products from animals that are penned up and fed corn tend to be very low in omega 3's.
Posted by Hugh on December 12, 2012, at 13:03:23
In reply to How do I lower pro-inflammatory cytokines?, posted by Trotter on December 11, 2012, at 2:55:57
Gamma linolenic acid (GLA) works well in combination with fish oil. Most people take way too much of it. Barry Sears (author of The Zone diet books) recommends taking tiny amounts of GLA -- only a few milligrams a week. (A capsule of evening primrose oil typically contains 90 mg of GLA.) What I do is prick a capsule with a pin, squeeze out a drop or two, and then keep the capsule in a sandwich bag in the refrigerator to use again in a few days. Also, you might want to try krill oil instead of fish oil. Krill oil has much more of an effect on my brain than fish oil.
Posted by Trotter on December 12, 2012, at 14:04:20
In reply to Re: How do I lower pro-inflammatory cytokines? » Trotter, posted by joe schmoe on December 12, 2012, at 6:58:51
I am convinced that we consume too much omega-6 and reducing same is beneficial. No argument from me.
Perhaps a reason you have not noticed any mood improvement from taking fish oil is that you have taken an oil with a EPA:DHA ratio of 3:2 or similar. All the data I have found shows that the only mood benefit is from EPA, and that taking DHA is actually counterproductive because EPA and DHA actually compete with each other. All the studies with EPA:DHA or 3:2 (or higher DHA) for mood have failed. All the successful trials have been EPA:DHA of 7:1 or higher.
The same applies to inhibiting inflammation. This is achieved by EPA, not DHA. In fact this may explain why EPA helps mood and DHA does not.
I see no reason to take much, if any, DHA since it competes with EPA (works against it). In fact the body can turn EPA to DHA, but not vice versa.
Posted by joe schmoe on December 12, 2012, at 17:19:44
In reply to Re: How do I lower pro-inflammatory cytokines? » joe schmoe, posted by Trotter on December 12, 2012, at 14:04:20
> I am convinced that we consume too much omega-6 and reducing same is beneficial. No argument from me.
>
> Perhaps a reason you have not noticed any mood improvement from taking fish oil is that you have taken an oil with a EPA:DHA ratio of 3:2 or similar. All the data I have found shows that the only mood benefit is from EPA, and that taking DHA is actually counterproductive because EPA and DHA actually compete with each other. All the studies with EPA:DHA or 3:2 (or higher DHA) for mood have failed. All the successful trials have been EPA:DHA of 7:1 or higher.
>
> The same applies to inhibiting inflammation. This is achieved by EPA, not DHA. In fact this may explain why EPA helps mood and DHA does not.
>
> I see no reason to take much, if any, DHA since it competes with EPA (works against it). In fact the body can turn EPA to DHA, but not vice versa.Interesting. I haven't paid that much attention to specific forms of omega 3 PUFAs.
You may be interested in this article on the essential polyunsaturated fatty acids by a lipid expert, Chris Masterjohn, who maintains "The Daily Lipid" blog. It seems to take a dim view of EPA.
http://www.westonaprice.org/know-your-fats/precious-yet-perilous
Posted by Trotter on December 12, 2012, at 19:11:10
In reply to Re: How do I lower pro-inflammatory cytokines? » Trotter, posted by joe schmoe on December 12, 2012, at 17:19:44
Yes, he seems to have nothing nice to say about EPA at all. A bit biased I suspect.
I am going to take 1050mg EPA and 150mg DHA (7:1) for depression. Some 'experts' say to take up to 4g EPA for depression, but there is no evidence to support using more than 1g. In fact in the only study of dosages for depression, 1g EPA was more effective than 2g or 4g. Also, I've taken 4g EPA in the past and I didn't notice any profound change in my mood.
I think EPA is a weak antidepressant at best (DHA not at all). It is probably most helpful to augment other antidepressant medications, something it has been shown to do. I doubt it is dose responsive. I suspect any benefit is purely from addressing an EPA deficiency in the western diet.
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.