PUFAs Cause Fatty Liver (and Reference To Mildronate)

Nov 21, 2015

Reduced mitochondrial fatty acid (FA) β-oxidation can cause accumulation of triglyceride in liver, while intake of eicosapentaenoic acid (EPA) has been recommended as a promising novel therapy to decrease hepatic triglyceride content. However, reduced mitochondrial FA β-oxidation also facilitates accumulation of EPA. To investigate the interplay between EPA administration, mitochondrial activity and hepatic triglyceride accumulation, we investigated the effects of EPA administration to carnitine-deficient mice with impaired mitochondrial FA β-oxidation. C57BL/6J mice received a high-fat diet supplemented or not with 3% EPA in the presence or absence of 500 mg mildronate/kg/day for 10 days. Liver mitochondrial and peroxisomal oxidation, lipid classes and FA composition were determined. Histological staining was performed and mRNA level of genes related to lipid metabolism and inflammation in liver and adipose tissue was determined. Levels of pro-inflammatory eicosanoids and cytokines were measured in plasma. The results showed that mildronate treatment decreased hepatic carnitine concentration and mitochondrial FA β-oxidation and induced severe triglyceride accumulation accompanied by elevated systemic inflammation. Surprisingly, inclusion of EPA in the diet exacerbated the mildronate-induced triglyceride accumulation. This was accompanied by a considerable increase of EPA accumulation while decreased total n-3/n-6 ratio in liver. However, inclusion of EPA in the diet attenuated the mildronate-induced mRNA expression of inflammatory genes in adipose tissue. Taken together, dietary supplementation with EPA exacerbated the triglyceride accumulation induced by impaired mitochondrial FA β-oxidation. Thus, further thorough evaluation of the potential risk of EPA supplementation as a therapy for NAFLD associated with impaired mitochondrial FA oxidation is warranted.

So this is interesting on two levels. One is that it is more mainstream science pointing to the harm from PUFAs.

And it is a warning for anyone messing around too much with mildronate I suppose.


Jan 6, 2015

Probably its first time I read a bad thing about mildronate!

Maybe in long term it can make this bad effect , or maybe you need to lower your fat intake on mildronate,as much as possible...and maybe cycle it!?


Sep 9, 2016
So, if one has bad fatty acid oxidation capacity then even a minor pufa fat intake would be bad!
So if someone can has successfully transitioned to becoming a fully fledged glucose/sugar oxidator (I don't know a better word) then even a small amount of pufa would cause more damage to liver than what it would have previously ?

Would it also mean that a person taking niacinamide+pufa will get fatty liver sooner than a person taking same amount of pufa without niacinamide.
This would also explain why high doses of niacin is correlated with fatty liver incidences.


Mar 20, 2015
So even in a healthy person with superb glucose oxidation & an antioxidant status that fights full force against nasties like lipid peroxidation, you still get ***t like this = PUFAs are always bad news.


Jul 8, 2015
mildronate seems to mess with creatine metabolism...anyone know much about that?
this would certainly incriminate someone on a high fat, particularly high pufa diet.
It would seem to offer little or no problem to those eating a low fat / low pufa diet.

Mildronate is an ischemic heart disease drug when used on label. Studies though sparse are encouraging.
I can't imagine those heart patients who responded favorably showed similar difficulties as seen in this study and the drug still being seen favorably.
I also can't imagine they'd be the healthiest of folks, they'd likely be rife with pufa damage and endogenous pufa excess
all interesting considerations


Oct 15, 2016
Interesting I wonder if the issues with mildronate would be seen with niacinamide too.


Dec 28, 2014
Dallas Texas
My mildronate experience so far tells me that my pufa consumption goes way down while taking it so the problem noted may not be a real world issue


Thread starter
Nov 21, 2015

The main mechanism of action of Mildronate is based on carnitine biosynthesis inhibition aimed to prevent accumulation of cytotoxic intermediate products of fatty acid beta- oxidation in ischemic tissues and to block this highly oxygen-consuming process. Alternatively the drug acts via stimulation of the nitric oxide production in the vascular endothelium through a modification of the γ-butyrobetaine and γ-butyrobetaine ester pools. The present review will summarize data on the Mildronate on different indications of the drug and its mechanisms of action.
Similar threads
Thread starter Title Forum Replies Date
Hans PUFAs Cause Obesity And Diabetes. Coconut Oil & Fructose Are Protective Articles & Scientific Studies 28
Peata PUFAs are real cause of skin aging Fats 4
T Our Ancestors Ate PUFAs (Probably) - Food For Thought Polyunsaturated Fats, Seed Oils 3
Inaut Ray Peat Interview with Tucker Goodrich, David Gornoski on PUFAs, Seed Oils, Benefits of Sugar, Milk Interviews 3
R Anti-Peat Mitigating PUFAs anti metabolic effect with increased calories intake Debate - Anti-Peat 9
hazel Lamb pufas? Meat 3
R PUFAS PUFAS AND PUFAS, how to remove Metabolism 5
V Marine PUFAs linked to lower mortality (Study) Polyunsaturated Fats, Seed Oils 4
Hans Excess PUFAs and low saturated fat could contribute to dementia Scientific Studies 1
Hans PUFAs, cardiolipin, ATP production and obesity Scientific Studies 6
Y Strong.Sistas - Dr Ray Peat Q&A | PUFAS, Fructose, Weight Loss, PCOS, Hormones, Cholesterol, & More Interviews 42
T Anti-Peat PUFAs Better Than Saturated Fats? Debate - Anti-Peat 125
ScurveDream Any Way To Reduce PUFAs In Pork Chops? Ask For Help or Advice 17
professor_sue Interview: Dr Ray Peat - Hormones, Stress, PUFAs, Low Carb Diets, Fat Burning Vs. Suga Video Interviews 4
murdoc Dr Ray Peat - Hormones, Stress, PUFAs, Low Carb Diets, Fat Burning Vs. Sugar Burning, & More! Interviews 2
F So Pufas Free And More Fruit Is The Way To Go Diet, Recipes 25
Z PUFAs + Curcumin New Research On Insulin Sensitivity Diet 3
Hans PUFAs Induce Apoptosis By Collapsing The Membrane Potential Polyunsaturated Fats, Seed Oils 2
Runenight201 The PUFAS Made Me Do It The Ray Peat Forum Lounge 12
J How Much PUFAs Should I Limit Myself To If I'm Relatively Young? Diet 25
S PUFAs And Their Influence On Political Leanings Political Talk, Alternative World Theories 185
Hans You Don't Need PUFAs (inflammation) To Grow Muscles Exercise 53
tankasnowgod Another Way PUFAs May Make You "fatter." Body Care 19
nigma WHY Do PUFAs Inhibit Thyroid? Ray Peat Topics 10
E How To Control PUFAs For Babies? Supplements, Pharmaceutical Drugs 9
ecstatichamster Studies? Where Is Evidence PUFAs Are Preferentially Stored Not Burned? Science 25
R How Much PUFAs Can I Get Away With? Ask For Help or Advice 29
Y Can The Human Body Make PUFAs From Other Substances? Ray Peat Topics 4
Y Cravings For PUFAs Diet, Recipes 32
A PUFAs Role On Skin Health 48
ecstatichamster Pufas Inhibit Glycolysis? Please Decode Scientific Studies 2
lvysaur Are Pufas Harmful In The Short Term? Digestion 4
Parsifal 2 questions about gut flora and PUFAs Ray Peat Topics 6
ecstatichamster Vitamin A Without PUFAs? A 12
natedawggh Zinc Neutralizes PUFAs (polyunsaturated Fats) In Vivo, Is Necessary For Weight Loss And Liver Lipid Supplements 29
zarrin77 Contradictory Information On PUFAs Polyunsaturated Fats, Seed Oils 24
uuy8778yyi is avoiding PUFAs the cornerstone of the diet Polyunsaturated Fats, Seed Oils 30
B Looking for recent studies that prove the harmfulness of PUFAs Articles & Scientific Studies 6
G Pufas Correlate With Autism Articles & Scientific Studies 0
burtlancast Fat-free Cultured Cells: No Need For PUFAS; Where Are The Studies ? Health 3
A Signs PUFAs Are Leaving The Body Health 4
R PUFAs Coming Up High on Cronometer Polyunsaturated Fats, Seed Oils 6
H PUFAS Polyunsaturated Fats, Seed Oils 3
D SFAs And PUFAs Health 4
M Pufas Polyunsaturated Fats, Seed Oils 2
J Free Fatty Acids: SFAs vs. PUFAs Diet, Recipes 6
taesch PUFAs and longevity Articles & Scientific Studies 1
S Do restaurants marinate meat in PUFAs? Eating Out, On The Run, Restaurants, Grocery Store 5
D PUFAS,Beta Carotene And Fruits Diet, Recipes 16
charlie Oops: PUFAs May Actually Increase Risk of Death in Patients, Fats 1

Similar threads