Could HDL cholesterol influence MS disease progression?

[ActiveMSers]

The question is gaining traction. Exercise influences HDL cholesterol (the good kind). Diet can influence HDL. And new research shows that some MS drugs do, too:

HDL-cholesterol elevation associated with fingolimod and dimethyl fumarate therapies in multiple sclerosis

S Blumenfeld Kan, E Staun-Ram, D Golan, ...
First Published October 14, 2019

https://doi.org/10.1177/2055217319882720


Abstract

Background
Patients with Multiple Sclerosis (PwMS) display altered lipoproteins levels and function, which seem to affect disease risk and progress. Whether disease-modifying therapies affect the lipoprotein profile in PwMS has scarcely been studied.

Objective
The study aims to assess whether fingolimod and dimethyl fumarate (DMF) affect lipoproteins in PwMS.

Methods
We compared retrospectively the blood lipoprotein levels of 29 fingolimod-treated and 41 DMF-treated patients before and after 3 and 12 months of therapy. Patients treated with cholesterol-reducing medications were not included. Data on weight change and disease activity during 1-year follow-up were obtained.

Results
HDL level, HDL/LDL ratio and HDL/total cholesterol ratio were increased in both treatment groups after 3 months’ therapy and sustained, with no change in LDL or triglycerides. While at baseline only 26% of patients met the recommended minimum of HDL 60 mg/dl, after 3 months’ therapy, 43% of fingolimod-treated and 47% of DMF-treated patients reached the recommended level. The majority of patients had no weight reduction.

Conclusions
Fingolimod and DMF therapies are associated with a specific increase in HDL in PwMS. Further studies are required to validate these findings and their potential implication as biomarker of reduced inflammatory state and/or reduced risk of neurodegeneration or cardiovascular comorbidity.

[Suebee]

I am really confused as to why the HDL/MS slowing disease progression connection is being studied in the context of a dmd. Is this because there is no money in studying how fish oil supplements (which increase HDL) can slow MS so scientists instead are looking to find a pharmaceutical way to increase HDL??? Have I missed something here?
For many years now, Fatty acid supplementation has been thought to slow MS progression based “ largely . . . on early research which showed that omega-3 could inhibit a certain protein (called matrix metalloproteinase-9) known to trigger inflammation in the [CNS]”
https://www.verywellhealth.com/omega...erosis-2440487

And Dr Swank, a.k.a The Swank Diet, developed over 40 years ago, connected good fats ( cod liver oil or fish oil) to reduced MS disability. Dr. Wahls writes” Swank believed MS had a vascular component... His diet is consistent with the cholesterol hypothesis of atherosclerosis that suggests saturated fat has deleterious effect on cerebrovascular health....Recent studies by other investigators found positive associations between worsening disability and total cholesterol and triglycerides levels and negative associations between HDL cholesterol and disability status of pwMS...”. https://doi.org/10.3390/nu11020352.

Further, Dr. Wahls’ diet “The WahlsElim diet encourages use of avocado, olive, sesame and sunflower oils which are sources of monounsaturated fatty acids. Flax, walnut and hemp oils are also encouraged as a source of alpha-linolenic acid, an essential fatty acid, but amounts are limited to two tablespoons per day to maintain balance in omega 6:3 ratio. Higher alpha-linolenic acid intake was associated with reduced risk of MS in the Nurses’ Health Study.” https://doi.org/10.3390/nu11020352

So why exactly is fingloid being studied to its connection to HDL? Maybe I’m missing something.

[Suebee]

Ok, admittedly I’m way way way above my pay grade ... but I noticed an ingredient in dimethyl fumarate looks connected to HDL levels so I throw this out there for you science people to analyze ....

1) premise : dimethyl fumarate
uses Nrf2 to reduce inflammatory process. New Oral Agents for Multiple Sclerosis: A Healthcare Professional's Guide
Medically reviewed by L. Anderson, PharmD Last updated on Apr 14, 2019.

2) premise: Nrf2 is well studied and known to reduce inflammation and modulate cholesterol in good way. https://doi.org/10.3389/fphar.2018.01308

3) Premise: Nrf2 can be found in natural sources like olive oil and nuts and natural sources can be used to increase HDL. Specifically, A Recent , “ (PREDIMED) trial reported that dietary polyphenols intake such as extra-virgin olive oil and nuts were associated with improved CVD risk factors and decreased inflammatory biomarkers levels in high CVD risk participants. It was shown that polyphenol intake decreased blood pressure (BP), increased plasma high density lipoprotein (HDL) and decreased the inflammatory biomarkers of CVD, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), IL-6, TNF-α as well as MCP-1”. https://doi.org/10.3389/fphar.2018.01308

4) If the above 3 premises are true, why did article posted conclude that increased HDL levels of patients who took dimethyl fumarate is a possible valuable bio marker for the DMD??? Is this not circular reasoning??? Wouldn't we expect HDL to increase if patient is compliant with this Oral drug, all things otherwise remaining equal? Isn’t it better to stick with quantifying how dimethyl fumarate reduces number of flares and severity, improves quality of life, etc. Seems like quantifying how an oral drug known to modulate HDL increases ones HDL is a useless value for measuring DMD. I’m not insulted at all if anyone can explain how I’m daft here.

[AMFADVENTURES]

I don't see the biomarker connection either. Seems like a stretch to me. However, fortuitous timing on bringing the article up as I just got the results of my lipid panel back yesterday and while my total cholesterol has always been somewhat high, as the article indicates for PwMS, it appears I've reached alarming new heights currently. Apparently Rituxan is NOT one of the DMD'S that increases HDL. Also, although I do exercise quite a bit, I have been more careless about my diet over the last year or two. So, heading back to previous eating habits and maybe even a statin for a while.

[AMFADVENTURES]

Bad HDL?

Suebee, thought you might enjoy this. Just had a physical with usual blood tests, PCP was on me to get on a satin and when blood tests came back with alarmingly high total cholesterol I said OK because of some of the information in this article, and I sent him the article.

He thought the article was quite interesting, he was aware of the relationship between statins, total cholesterol reduction and likely benefit to PwMS. But, and here's the interesting part, he said there are recent studies indicating that not all HDL cholesterol is necessarily good, there may be such a thing as bad HDL!!! Thought you might find that particularly interesting. I know I'll be keeping my eyes open.

Larry