Hey My Dudes [PUFA, Ketosis, Insulin Resistance]

[BigYellowLemon]

Those ETC points are quite valid, but I think the point on PUFA being insulin sensitizing is incorrect. PUFA is a direct insulin receptor antagonist, so it will prevent it from doing its job and make you insulin resistant.
Polyunsaturated fatty acid-mediated suppression of insulin-dependent gene expression of lipogenic enzymes in rat liver. - PubMed - NCBI
"...The effects of dietary polyunsaturated fat on insulin-dependent gene expression of lipogenic enzymes and a possible mechanism for PUFA-mediated suppression of the gene expression have been investigated in rat livers. When diabetic rats were injected with insulin, the insulin dose-dependent induction of lipogenic enzyme mRNAs were markedly reduced with increasing dietary corn oil. On the other hand, the PUFA-mediated suppression of the mRNA concentrations was partially restored by treatment with pioglitazone, a candidate for increasing insulin receptor phosphorylation. Moreover, insulin binding to receptors of liver, receptor autophosphorylation, and kinase activity toward exogenous substrate were lower in the corn oil diet group than in the hydrogenated fat group. The PUFA-mediated suppression of insulin binding was somewhat restored by pioglitazone, and the suppression of insulin receptor phosphorylation was significantly restored. It is suggested that the PUFA-mediated suppression of insulin-dependent gene expression of lipogenic enzymes can be ascribed to a decrease in insulin receptor binding primarily and also to receptor phosphorylation. Thus, PUFA appears to suppress the lipogenic enzyme gene expression stimulated by insulin."

Also, PUFA is the primary inducer of NF-kB and that protein is perhaps THE main player in insulin resistance and diabetes II. There is a reason aspirin, glycine, and progesterone can cure diabetes II and insulin resistance - i.e. they all lower levels of NF-kB, as well as TNFa and such, and none of these are upregulated by saturated fat. So, diabetes is primarily an inflammatory condition, which is supported by the fact that cortisol production is upregulated in diabetes. Saturated fats, especially MCT like coconut oil and butter are insulin sensitizing when eaten without PUFA. The reason superoxide ions are created in the ETC is usually excessive NO production, to which PUFA also contributed. Saturated fat and carbs on their own do not create dangerous levels of superoxides.
So, the TLDR of my rant is this - ANY fat will make you temporarily insulin resistant due to the Randle cycle. However, ONLY the PUFA will give you diabetes and chronic insulin resistance due to its interference with the insulin "receptor" expression and binding profile, induction of inflammation (NF-kB, TNFa, prostaglandins, leukotrienes, etc) and damaging of the beta cells of the pancreas. Saturated fat has none of these effects.
Just my 2c.

Hmm, very interesting!

I'm not sure how I feel about this study. They used diabetic rats, fed them PUFA, and then injected them with insulin. It seems artificial to me.

When I said that PUFA was insulin sensitizing, I wasn't saying that like it was a good thing.

Here's a post by tyw, if you haven't seen it: Fructose Alters Brain Genes Negatively. How To Counter This From Peat Perspective?

Here's the Hyperlipid article on fatty acids and superoxide bursts, which can result in insulin resistance or sensitivity: Hyperlipid: Protons: FADH2:NADH ratios and MUFA

Hmm, it seems that PUFA displays insulin sensitizing effects at low-levels but shut's down insulin signalling at high-levels. At either level, it seems to mess with proper insulin signalling. So even though it is insulin sensitizing at low-levels, it's not the proper/normal/physiological insulin signalling that the body likes.

 

[Tarmander]

Why would you be scared of raising FFA's to induce uncoupling? Uncoupling is (generally) great! Especially when the uncoupler is an energetic substrate itself.

Yes, Peter mentions that a lot. His reasoning is probably this: in someone with a broken complex 1, it would be better to obtain their energy from saturated fat via FADH2, vs carbohydrate, which favors NADH. If you feed someone with a broken complex 1 carbohydrates, then they will suffer from extreme amounts of reverse electron flow (making them insulin resistant). Saturated fat driven metabolism side-steps this and allows the mitochondria to prosper.

Does CO2 increase complex 1? Does it help carbohydrate metabolism?

Uncoupling is pretty cool, but doing it through FFA seems overly risky to me when you can use substances like caffeine, MB, Aspirin, etc that will induce it safely. High FFA is pretty common in most degenerative diseases so why bother. CO2 helps pretty much all metabolism.

 

[BigYellowLemon]

Uncoupling is pretty cool, but doing it through FFA seems overly risky to me when you can use substances like caffeine, MB, Aspirin, etc that will induce it safely. High FFA is pretty common in most degenerative diseases so why bother. CO2 helps pretty much all metabolism.

I think uncoupling is great. I think it's less risky when the uncoupler itself can be used for ATP. Aspirin and caffeine are great, but they could under some circumstances deplete ATP, whilst SFA's would have a failsafe mechanism, as in, they would be used for energy and uncouple at the same time. I'm not ragging on aspirin or caffeine though. I like them a lot. Especially caffeine.

I think the FFA seen in disease states might be the body trying to support itself. It's a symptom, not a cause of the disease. Just like cortisol turning muscles/amino-acids into sugar. You wouldn't say that sugar is bad, right?

Caffeine and methylene blue seem to support beta-oxidation. Aspirin sadly not.

I like CO2, I like pranayama/buteyko. It makes me feel very calm and hot.

 

[tyw]

@jayegray and @BigYellowLemon

I do not believe in "ideal fuel" ..... Eat what doesn't cause you stress, and let the macronutrients fall where they may.

The key though, is to have an effective measure for "foods that cause you stress".

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@haidut What Peter @ Hyperlipid is talking about when he says "PUFA are insulin sensitising", is specifically the result of beta oxidation of already present fatty acids, and the resultant NADH:FADH2 ratios produced by various fatty acids.

This explanation assumes that fatty acids have full access to Mitochondrial Electron Chain Transport (ECT), and the result is that insulin is still permitted to function despite an acute burst of PUFA. Insulin would function to a much lesser degree if SFA were put through ECT.

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Next, the actual referenced study -- Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans | Diabetes

Again, this is an overfeeding study, and it is both a relative measure, as well as an acute measure.

• "Relative" in the sense that it a comparison between SFA in caloric excess and PUFA in caloric excess. It is not even a comparison between SFA and PUFA in caloric sufficient diets. Again, the caloric excess component is important.
  
  And of of other comparisons? eg: PUFA vs SFA with varying fat macronutrient percentages in the context of overfeeding. Different caloric levels of overfeeding (this study was 750kcal a day, but who actually eats "only 750kcal more" when they go all out with food .....).
  
  
• "Acute" in the sense that all this measures is how each fat causes changes in fat storage patterns in the context of a large and transient caloric bolus. SFA fat empirically caused more fat gain in this study, and quite a fair bit more, in the "wrong" places. See Figure 2 from the study:
  
  (click to enlarge)
  
  You can already start to see some changes in gene expression toward what I would call "unfavourable" (see Table 5), but it seems like during the short term nature of the study, it doesn't seem to affect the outcome much.

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The case for chronic PUFA exposure and resulting negative systemic effects has already been made on this forum many times. These harms are very significant, and it is still my opinion that PUFA consumption be heavily limited.

That is completely compatible with partitioning of acute fat gain during PUFA overfeeding, lesser towards visceral and liver stores, when compared with SFA overfeeding.

....

 

[Emstar1892]

I was ketogenic for almost 3 years. Like other people, euphoria at first, insulin resistance and hypothyroidism after. But, I am only a case study of one.

If you plan to drop carbs without full ketosis (>40g) do you think you can avoid muscle loss?

 

[haidut]

I was ketogenic for almost 3 years. Like other people, euphoria at first, insulin resistance and hypothyroidism after. But, I am only a case study of one.

If you plan to drop carbs without full ketosis (>40g) do you think you can avoid muscle loss?

There is some evidence that higher dose of the electrolyte minerals can prevent the muscle loss from cortisol to a great degree. Progesterone/pregnenolone may be able to do same, as should any other glucocorticoid "receptor" antagonist. DHT is another such antagonist. But then again, the body needs its sugar so even if you prevent muscle breakdown you may get liver toxicity. The brain also starts to degenerate unless at least some sugar is available. I mean, you'll live, but higher cognitive functions will deteriorate.

 

[jyb]

I think the FFA seen in disease states might be the body trying to support itself. It's a symptom, not a cause of the disease. Just like cortisol turning muscles/amino-acids into sugar. You wouldn't say that sugar is bad, right?

I think the same. RP raises an interesting point that is CO2 in favour of carbohydrate metabolism, however when he merely mentions FFA / disease association it is both expected and not very informative for the situation you describe here (non disease, high sat fat, low pufa).

 

[BigYellowLemon]

I was ketogenic for almost 3 years. Like other people, euphoria at first, insulin resistance and hypothyroidism after. But, I am only a case study of one.

If you plan to drop carbs without full ketosis (>40g) do you think you can avoid muscle loss?

Hmm. I think you'll be fine in terms of muscle, if you keep carbs above 40g. Too little carbs and I feel as though the cortisol and adrenaline will cannibalize your muscles. Above 40g, you should be good. I think there's a lot of lee-way with carbs in a HFLC diet, just keep carbs under 100g I think. I've been doing around 80g or higher a day on a high-fat diet and I'm adapting well.

I think your brain will be fine. The insulin resistance should be a good thing. On a HFLC diet, your blood sugar will be pretty high. This is good. While your body is insulin resistant (because it's consuming SFA's), the carbohydrates will have now have no where to go except your blood, where they'll be consumed by your brain. This is optimal in my view. It kind of gives your brain a guaranteed source of fuel. Also, if you manage to have a few ketones in your blood, that'll feed your brain as well, with some additional benefits (GABA/glycine effect, increased ATP

Also, to add on to what haidut mentioned, electrolytes can be a little wonky while your adapting to ketosis. Many people recommend consuming a good amount of salt while on a HFLC diet. Here's a comment on reddit that explains it: How much salt do you eat? • /r/keto.

People on a HFLC diet eat the wrong things in my view. Keep it simple. Dairy and meat, coconut oil too if you don't feel weak from it (I do, coconut oil might not be best for HFLC diet). No avocados or peanut butter or almond flour, like I see so many people doing.

Did you get hypothyroidism from a ketogenic diet? If so, I'm sorry. Do what feels best.

 

[BigYellowLemon]

I wish you nothing but luck. Make sure you document everything. And try to tweak only one parameter at a time (I tend to fail on both counts).

I do know that many people feel like ketones are much more efficient for the heart and the brain. So it's a worthwhile experiment.

I will for sure keep you posted on my results. I will also try to keep things steady and in routine, as you say.

I have read that the heart greatly prefers fatty acids (SFA!). That's one reason why I don't feel comfortable using niacinamide and aspirin whilst on a HCLF diet. Sure, you won't block all FFA in the blood, but still.

Thank you for your kind words.

 

[tara]

My question is, is CO2 good for carbohydrate metabolism, or metabolism in general?

I think good levels of CO2 are good for carbohydrate metabolism and for metabolism in general, and the flow of CO2 from cells helps bring oxygen towards those cells. And if effective carbohydrate oxidation produces a higher level of CO2 per oxygen, this may make it a particularly good fuel for general metabolism. (Though cells in different tissues have tendencies of their own - some tissues tend to burn fat and some will be more likely to burn sugars when available. And once carbohydrate metabolism is damaged, we may all be in different spaces wrt what will work best for us.

Also, I'm not sure how I feel about fasting. I think it can be good for some people, sometimes, but not for sick people.

Some (relatively healthy) people have better glycogen storage, and can fast for longer before it runs low enough to get stressful.
And it seems possible to me that there might be some occasional good uses for fasting a bit beyond that, for particular issues.

 

[Elie]

Yeah, in deep ketosis with very little carbs, cortisol rises, and I'm pretty sure adrenaline too.

I think that's why so many people have bad results with HFLC diets, they either cut carbs too much or use PUFA's instead of SFA's.

I would suggest getting more than 50g of carbs if you're doing HFLC.

I might try a HCLF diet soon. It's all very confusing.

So in you mind, what would be the ideal macronutrient ratio to lower blood sugar in diabetics and to loose fat in overweight people?

 

[Emstar1892]

Hmm. I think you'll be fine in terms of muscle, if you keep carbs above 40g. Too little carbs and I feel as though the cortisol and adrenaline will cannibalize your muscles. Above 40g, you should be good. I think there's a lot of lee-way with carbs in a HFLC diet, just keep carbs under 100g I think. I've been doing around 80g or higher a day on a high-fat diet and I'm adapting well.

How are you measuring the quality of your adaptation?

Interesting on the net carb front - I was under the impression that when producing and utilizing ketones at high quantities, the body would (after a month or so) stop overshooting cortisol and cannibalizing muscle, although it would obviously do this at first. With carbs higher than 40g, and therefore only having transient (if any) ketogenic episodes, wouldn't the body find it harder to adapt and utilize fats as a main fuel source, since you keep 'reassuring it' by adding carbs back? In the latter case, therefore, aren't you more likely to keep up-regulating cortisol? And if so, aren't you therefore more vulnerable to muscle loss than if you were VLC?

I can't say that VLC caused hypothyroidism directly and independently of other variables but the correlation of symptoms and dietary changes and timescale are very suspect.

Also, why should blood sugar be high in ketosis? My hbA1c after 19 months of ketosis came out at 4.4 - pretty textbook, no?

 

[Tarmander]

I think the FFA seen in disease states might be the body trying to support itself. It's a symptom, not a cause of the disease. Just like cortisol turning muscles/amino-acids into sugar. You wouldn't say that sugar is bad, right?

I mean...do you think that or do you know that? When I take niacinamide, which drastically lowers FFA, I feel amazing. Do whatever you want, if you want to live the high fat life go for it, you can do whatever you like you know.

 

[BigYellowLemon]

I mean...do you think that or do you know that? When I take niacinamide, which drastically lowers FFA, I feel amazing. Do whatever you want, if you want to live the high fat life go for it, you can do whatever you like you know.

Hmm, interesting.

I'm just trying to create discussion about the merits and detriments of either diet. I think I will actually be doing a HCLF diet now, lol.

It doesn't make sense to me why we would burn for fuel, what we're made of. That would be like a car burning metal as fuel. Also, I don't want to miss out on the benefits of insulin.

Have you tried aspirin? What are your thoughts on it?

 

[BigYellowLemon]

How are you measuring the quality of your adaptation?

Interesting on the net carb front - I was under the impression that when producing and utilizing ketones at high quantities, the body would (after a month or so) stop overshooting cortisol and cannibalizing muscle, although it would obviously do this at first. With carbs higher than 40g, and therefore only having transient (if any) ketogenic episodes, wouldn't the body find it harder to adapt and utilize fats as a main fuel source, since you keep 'reassuring it' by adding carbs back? In the latter case, therefore, aren't you more likely to keep up-regulating cortisol? And if so, aren't you therefore more vulnerable to muscle loss than if you were VLC?

I can't say that VLC caused hypothyroidism directly and independently of other variables but the correlation of symptoms and dietary changes and timescale are very suspect.

Also, why should blood sugar be high in ketosis? My hbA1c after 19 months of ketosis came out at 4.4 - pretty textbook, no?

I'm not using anything other than how I feel. I've been getting nauseous this week. I haven't really been eating super low carbs though, so I could be skewing the results.

I'm not sure about that. I would have to look into the cortisol and carbs and muscle wasting. I'm not receiving any thoughts on the matter yet.

Blood sugar should be high, because the carbs you would be consuming would have no where to go except your brain. Most of your body would be insulin resistant, and thus would not be able to transport glucose into your cells.

I think that if you're eating fructose, or eating a lot of PUFA, than your blood sugar would be low on a ketogenic diet. Were you doing any of those things?

Fructose I imagine would keep your blood sugar low, because fructose doesn't need as much or any insulin to enter the cell, thus even if you were insulin resistant on a HFLC diet, the fructose could still enter

or

perhaps you were eating a lot of PUFA, which didn't create a lot of insulin resistance (low-level), and thus glucose could still enter your cells.

If you were eating a lot of PUFA on a HFLC diet, then that might also be why you became hypothyroid.

 

[BigYellowLemon]

So in you mind, what would be the ideal macronutrient ratio to lower blood sugar in diabetics and to loose fat in overweight people?

As Yew said, eat what isn't stressful and let the macro-nutrients fall where they may.



From my limited understanding, I would suggest a HCLF diet, use small amounts of aspirin, drink lots of coffee/use caffeine, and make sure you get ALL of your micronutrients.

But, I warn you, I don't know enough about you nor biology to recommend a guaranteed diet that will work.

A HFLC diet might also work.

May I ask what you're doing now?

All the best.

 

[Tarmander]

Hmm, interesting.

I'm just trying to create discussion about the merits and detriments of either diet. I think I will actually be doing a HCLF diet now, lol.

It doesn't make sense to me why we would burn for fuel, what we're made of. That would be like a car burning metal as fuel. Also, I don't want to miss out on the benefits of insulin.

Have you tried aspirin? What are your thoughts on it?

Yeah I've used aspirin before. I probably take it once or twice a week. Always makes me feel manly on the day I take it. Too much causes me insomnia.

If you are trying to figure out what type of diet you should do, hflc or hclf, you have to look at your context.

If your occupation involves a lot of having to be "on" for hours at a time(i.e. Truck driver, phone sales, customer service, grad student, computer programmer), then cutting fat out of your diet is going to be very difficult. You'll feel like absolute carpools. Think of kids who burn mostly sugar; high energy then crash, then high energy, etc.

If your life is more about quality of performance, like a public speaker, an actor, that kind of thing, then cutting sugar out of your diet is going to make you pretty dull and bad at what you do.

Also, the amount of sun your get can determine how much sugar you can do vs fat. A lot of those Hawaii boys and gals don't do much fat when they live on the beach.

Don't stray too much from your context with your diet, you'll just suffer. Or change your context to the one you want to eat.

 

[Elie]

As Yew said, eat what isn't stressful and let the macro-nutrients fall where they may.



From my limited understanding, I would suggest a HCLF diet, use small amounts of aspirin, drink lots of coffee/use caffeine, and make sure you get ALL of your micronutrients.

But, I warn you, I don't know enough about you nor biology to recommend a guaranteed diet that will work.

A HFLC diet might also work.

May I ask what you're doing now?

All the best.

Thanks for asking.
you know what, I am not tracking caloric intake well, but I would estimate about 200 calories similar ratio of macros as you, about 1400 from carbs (fruit, juice, rice or potatoes or pasta once a day), about 100g (5protein, 400cal) from skim-1% milk, cottage cheese, a bit of mozzarella, bit of meat and fish, and approx 20g fat. Drink 1-3 cups of coffee daily, Aspin, niacinamide and multi mix with lysine proline and glycine on most days. Light weight bearing exercise a few times a week (crunches, push ups, squats, etc.) , just for a few minutes. problem is I can't get rid of my "love handles". i used to weight 180-185 and be slim, nor I am 197-200 and chubby. I am 5'11". I am actually a naturopathic doctor, and am getting descent results with my patients with this approach-75% success with weight loss and about the same with diabetes (of those who comply), but I can't shake off my extra 10lb. As well, I'd love to find a system that enables me to identify the 25% who don't respond well to HCLF.

 

[BigYellowLemon]

Thanks for asking.
you know what, I am not tracking caloric intake well, but I would estimate about 200 calories similar ratio of macros as you, about 1400 from carbs (fruit, juice, rice or potatoes or pasta once a day), about 100g (5protein, 400cal) from skim-1% milk, cottage cheese, a bit of mozzarella, bit of meat and fish, and approx 20g fat. Drink 1-3 cups of coffee daily, Aspin, niacinamide and multi mix with lysine proline and glycine on most days. Light weight bearing exercise a few times a week (crunches, push ups, squats, etc.) , just for a few minutes. problem is I can't get rid of my "love handles". i used to weight 180-185 and be slim, nor I am 197-200 and chubby. I am 5'11". I am actually a naturopathic doctor, and am getting descent results with my patients with this approach-75% success with weight loss and about the same with diabetes (of those who comply), but I can't shake off my extra 10lb. As well, I'd love to find a system that enables me to identify the 25% who don't respond well to HCLF.

That guy in the video I linked is not me. He seems to be doing things that work for him though. Idk why I linked him, but I like his story and results. He lost weight eating 3000+ calories a day! And it was mostly sugar!

Get those coffee numbers up! Haha. If you notice coffee as a good effect, I suggest drinking more. I used to be scared of drinking lot's of coffee, but after reading about Ray drinking 50 cups a day, I boosted my numbers up. However, go slow. Coffee can be stressful if your body isn't used to it. Also I don't know enough to really recommend you do more.

I am very curious on why you aren't losing weight. Maybe cut out the fish? How much of the 20g of fat is PUFA? and are you absolutely sure you're eating low-fat? You seem to be eating a lot of dairy, some of it with fat. I would cut out a lot of the dairy, and meat/fish. I would replace the meat and fish with gelatin. I would only drink skim milk, or fat-free cheese. Actually, I think you could eat all of those dairy products, just make sure they're fat-free. Get your fat from ghee/butter or coconut oil. If that doesn't make a difference within a week or two, up the fat. to around 33% of the dietary macronutrients, and get carbs up to around 33% as well. If you feel better from that, perhaps try pushing fats up even higher. If too much fat makes you feel bad, then of course lower it.

Also, though aspirin and niacinamide are pretty good in my book, they seem to inhibit fat release and oxidation. Aspirin is an uncoupler, but still. Maybe try taking aspirin out and seeing

Do you feel healthy? If not, perhaps a HFLC diet should be considered.

Normally when people go so low-fat and such high-carbs, as you seem to be doing, they lose weight FAST and become skinny as hell.

Are you stressed? Sleep?

Take everything I say with a grain of salt. I myself am skinny, and have always been skinny. Though I know a bit about weight-loss methods through research and reading, I myself have no direct experience, as I have always been under/around 7-9% BF, maybe even lower. BTW, I want to gain weight. Right now I'm about 5'10, 115-120lb ! ! ! It fluctuates.

 

[Elie]

Good points. I do add gelatin every day. Will use fat free cottage for a couple of weeks and see. and if still no cigar then try 33% carbs 33% fat. Will up the coffee, maybe even try caffeine pills.
I actually do feel healthy. I have had lots on my plate with family life and work and do cycle through periods of stress. Last winter stress was especially high, but for the first time in a long time I had no significant colds and flues and I attribute this to the effect of HCLF on stress. I do make sure to get 7-8 hours of sleep. Would love to go down to 9% of body fat, even bit higher will do. But all in all I do feel healthy. Thanks for your suggestions!