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Testing Liver After 8 months on diet.

Hey John, this might interest you. An interesting study on the use of fat and the levels of Retinol Binding Protein. Olive oil did not seem to fare well in this study.

The Effect of Different High Fat Diets on Plasma Concentration and Hepatic Expression of Retinol-Binding Protein 4 in Rats

 

Retinol-binding protein 4 (RBP4) has been associated with insulin resistance and hepatic steatosis. Production of hepatic insulin resistance by high-fat diets depends on their fatty acid composition. Here, the effect of three high-fat diets on plasma concentration and hepatic expression of RBP4 (Rbp4) was compared with respect to insulin resistance, dyslipidemia, and hepatic steatosis.

Weight-matched groups (N=10/group) of male Sprague-Dawley rats received one of four diets for eight weeks: low-fat control (LF, 15% kcal as fat), or a high-fat (HF, 55% kcal as fat) safflower oil (polyunsaturated), olive oil (cis-monounsaturated, MUFA) or a trans-fat (trans-MUFA) diet. Blood samples were collected as a time course study at wks 3, 6, and 9 (N=16), and after an eight-week feeding in the fasted or refed (fat-free, high carbohydrate meal) state (N=40). Liver samples were collected at wk 9 in the fasted or refed state to compare plasma concentration and hepatic expression of RBP4 (Rbp4) and its response to insulin. Plasma RBP4 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Hepatic expression of Rbp4 and other genes (e.g. Srebf, Fasn) was measured by real-time PCR.

Body weights and percent body fat of all HF groups were similar at wk 9. Plasma RBP4 concentrations were higher in the trans-fat vs. the LF group at wk 3, 6, and 9 (p< 0.05). The olive oil and the trans-fat group had elevated plasma RBP4 at wk 9 vs. the LF group (p<0.05). Liver expression ofRbp4under fasted or re-fed conditions did not differ among the groups, a finding consistent with a non-hepatic (e.g. adipose tissue) source of RBP4. The olive oil group had higher fasting plasma insulin levels (p<0.05), higher HOMA-IR values (p<0.005), higher liver lipid concentration (p < 0.05) vs. other groups. Expression of hepatic genes in the lipogenic pathway was positively correlated with plasma triglyceride levels in both the olive oil and trans-fat groups (p< 0.05), and the olive oil group had greater stimulation of lipogenic gene expression by refeeding than did other groups (p<0.05). The HF safflower group did not show differences from the LF group at wk 9.

The HF olive oil (cis-MUFA) diet was associated with elevated plasma RBP4, hyperinsulinemia, hepatic steatosis and insulin resistance, as well as an enhanced hepatic expression of lipogenic genes. The HF trans-fat (trans-MUFA) diet was also associated with elevated plasma RBP4 and increased lipogenic gene expression, and both MUFA groups showed this expression to be correlated with plasma triglyceride levels. These findings show that HF diet-induced increases in RBP4 are dependent on the type of fat and suggest that non-hepatic RBP4 may promote hepatic expression of lipogenic genes.

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Quote from YH on April 5, 2019, 12:43 pm

Hey @Bella, I scooped up my results to see how they compare, and I included the description that was provided on Promethease:

rs12934922-rs12934922(A;T)

Reduced conversion of beta-carotene to retinol Associated with Rs7501331 and reduced BCMO1, lower ability to convert beta-carotene to retinyl esters and higher serum beta-carotene levels. See also Rs7501331
rs12934922 (R267S) and rs7501331 (A379V) double mutant have a reduced catalytic activity of beta-carotene by 57%. Female volunteers carrying the T variant of rs7501331 (379V) had a 32% lower ability to convert Beta-carotene, and those carrying at least one T in both SNPs show a 69% lower ability to convert Beta-carotene into retinyl esters. rs7501331: the frequency of the wild-type C allele and variant T allele was 76 and 24%, respectively; 56% of the population was CC wild-type genotype, and 39% was heterozygote CT with the TT variant present in 5% of the population. rs12934922: the frequency of the wild-type A allele and variant T allele was 58 and 42%, respectively; 38% of the population was AA wild-type genotype, 40% was heterozygote AT, and 22% was TT homozygote 
 more info
normal
rs6564851(G) associated with higher beta-carotene (p = 1.6 x 10(-24)) and alpha-carotene (p = 0.0001) levels and lower lycopene (0.003), zeaxanthin (p = 1.3 x 10(-5)), and lutein (p = 7.3 x 10(-15)) levels, with effect sizes ranging from 0.10-0.28 SDs per allele. Note that low plasma levels of carotenoids and tocopherols are associated with increased risk of chronic disease and disability, yet dietary intake of these lipid-soluble antioxidant vitamins is only poorly correlated with plasma levels, leading to the hypothesis that it isn't what you eat, it's your SNPs that regulate your carotenoid levels. This is one of the SNPs reported by NutraHacker SNPs. 
 more info
This is one of the SNPs reported by NutraHacker SNPs. Common variation in the beta-carotene 15,15'-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study.
Reduced conversion of beta-carotene to retinol Associated with Rs7501331 and reduced BCMO1, lower ability to convert beta-carotene to retinyl esters and higher serum beta-carotene levels. See also Rs7501331
rs12934922 (R267S) and rs7501331 (A379V) double mutant have a reduced catalytic activity of beta-carotene by 57%. Female volunteers carrying the T variant of rs7501331 (379V) had a 32% lower ability to convert Beta-carotene, and those carrying at least one T in both SNPs show a 69% lower ability to convert Beta-carotene into retinyl esters. rs7501331: the frequency of the wild-type C allele and variant T allele was 76 and 24%, respectively; 56% of the population was CC wild-type genotype, and 39% was heterozygote CT with the TT variant present in 5% of the population. rs12934922: the frequency of the wild-type A allele and variant T allele was 58 and 42%, respectively; 38% of the population was AA wild-type genotype, 40% was heterozygote AT, and 22% was TT homozygote
Thanks YH, that's super helpful! I can't thank you enough!

 

Thanks @yh, that was super helpful! I can't thank you enough. I'm not sure what went wrong in my post above but I wanted to thank you.

@bella

No problem! I'm finding all this very interesting.

Quote from YH on April 5, 2019, 2:11 pm

@bella

No problem! I'm finding all this very interesting.

Me too! I feel like I dodged a lethal bullet in all honesty. It is proof that my past experiences with poor health have a very logical explanation specific to my genetic makeup. I still believe Grant's theory is most likely correct and I won't be changing anything I'm doing but it does help further explain why eating the rainbow and all of that had such a profoundly negative impact on me.

YH - that's a useful study, very interesting, thanks! I've been on the Methionine Restriction hunt today and there's a high-fat context in the abstract, but not any detail on which fats.

Pleiotropic responses to methionine restriction. Exp Gerontol.       2017 Aug   https://www.ncbi.nlm.nih.gov/pubmed/28108330

Methionine restriction (MR) extends lifespan across different species. The main responses of rodent models to MR are well-documented in adipose tissue (AT) and liver, which have reduced mass and improved insulin sensitivity, respectively. Recently, molecular mechanisms that improve healthspan have been identified in both organs during MR.

In fat, MR induced a futile lipid cycle concomitant with beige AT accumulation, producing elevated energy expenditure. In liver, MR upregulated fibroblast growth factor 21 and improved glucose metabolism in aged mice and in response to a high-fat diet. Furthermore, MR also reduces mitochondrial oxidative stress in various organs such as liver, heart, kidneys, and brain. Other effects of MR have also been reported in such areas as cardiac function in response to hyperhomocysteinemia (HHcy), identification of molecular mechanisms in bone development, and enhanced epithelial tight junction.

In addition, rodent models of cancer responded positively to MR, as has been reported in colon, prostate, and breast cancer studies. The beneficial effects of MR have also been documented in a number of invertebrate model organisms, including yeast, nematodes, and fruit flies. MR not only promotes extended longevity in these organisms, but in the case of yeast has also been shown to improve stress tolerance. In addition, expression analyses of yeast and Drosophila undergoing MR have identified multiple candidate mediators of the beneficial effects of MR in these models. In this review, we emphasize other in vivo effects of MR such as in cardiovascular function, bone development, epithelial tight junction, and cancer. We also discuss the effects of MR in invertebrates.

That's interesting John. I have specifically been reducing my protein intake last week due to several genetic issues that are negatively affected by high protein intake. I'm wondering if the reduced methionine has something to do with it.

 

To further update this thread, I have had chicken liver pate twice since due to liver cravings. So far, I have mostly had positive effects. My mood has been very calm. I am feeling comfortably warm and I sweat easily when working out. No breakouts on my skin. My skin looks lighter in color with no blemishes on my back or face. My eyesight has become very clear to the point where I can walk and pick up on details that I normally don't pick up on. No need for sunglasses at all. My neck was a little red from working in the sun, but is now very clear. Also no dandruff, ingrown hairs, calluses or any of the other problems I've had before.

Also, my eye color has been getting remarkably green and the whites of my eyes have been very white. The one problem that I had while not eating Vitamin A is that my pupils would get very dilated to the point where I looked like a vampire(it took me a while to notice, but people would not look me in the eye). My eye color was also very dull. Whenever I consume foods with Vitamin A, my eyes brighten again and I look human again.

In addition to the liver consumption, I've been drinking more milk, eating more butter, and some cheese. Somedays I've gotten close to a liter of milk without any digestive issues at all.  This is surprising since I am technically lactose intolerant. I expected bloating after not having milk for a while, but it's been having the opposite affect. My pants feel looser again. I also expected some spinal issues to return, but my spine has been feeling very stable and flexible.

Overall, my desire for meat(burgers, steak, chicken filet) has severely reduced. No more than 4 oz, and some days I eat none. I also have not bothered with eggs since they still disgust me.

My macro nutrients work out as follows:

30-40 grams of animal protein(milk, cheese, bacon, liver pate, some meat);

30-40 grams of plant protein(bread, beans, potatoes, rice)

Some green vegetables, onions, and white vegetables.

The only fruits i eat are currents, dates, and pears. Pineapple, when it's around.

 

Carbs are at about 250-300 grams a day.

Total fat intake ranges from 50-70 grams a day. I've also been having only one cup of a coffee a day(down from 4) since I no longer crave it much.

 

My theory as to why this diet helped, was because I was depleting a lot of the beta carotene and synthetic forms of Vitamin A which I think were causing the problems. My genetics test points to certain mutations that cause issues with processing Beta-Carotene. Additionally, I have a genetic issues with sulphur, and certain amino acids that are found in animal products(especially muscle meats). When I keep my protein intake adequate, and my fat intake in a normal range, I don't seem to have any issues with Vitamin A. When I eat too much meat or too much starch, I start to get "detox" symptoms. Overall, I'm tolerating a lot more foods, and I feel pretty solid. I even had some tomatoes with cheese over the weekend and had no issues. I'm really beginning to think that diet is something very specific to the individual. I've actually been talking to my grandmother and asking her what they've were eating growing up. My family comes from a long line of pastoralist, and largely lived off what they produced. Needless to say, they barely had any beta carotene, salmon, or avocados. But they did eat a lot of dairy products, chickens, chicken fat, and also liver. Lamb and beef was often smoked, so they can have a few ounces of meat every day.

 

 

Is everything still going well with your diet changes?

@bella I'm still alive! This is a little long winded, but I've been thinking a lot about this.

In my zeal, I ate some chopped beef liver salad over the weekend. Only about a tablespoon. I made sure to eat it with muscle meat. This is in addition to the chicken liver pate I had during the week. I responded decently well. What I found interesting was that I've been repulsed by dairy products since I tried the beef liver. Every time I was reaching for the milk or cheese, I'd even feel an itching sensation in my entire body, which I found to be very odd. Needless to say, I've been listening to my body, and avoiding dairy products  for the last few days. Also, after I tried the beef liver, my appetite was completely blunted for 18 hours. I even skipped dinner that night and went to sleep. I wasn't even that hungry for breakfast the following morning.

I honestly cannot say if the experiment was good or bad. My mood has thankfully remained the same. But I've been experiencing some dryness on my face and the bottom of my heels. I've been eating low vitamin A during this week. I feel like I still have a way to go in terms of improving my health. I've noticing some moles on my stomach are changing shapes. I don't know if I should be worried or not, but I remember my doctor told me to call him if they start becoming irregular. I don't know what the relationship between vitamin A and moles is yet, as so little research is done on moles. I've been losing color on a few moles, which has basically been my point of reference, as to whether this diet is an improvement or not, since I haven't experienced any rashes or mood changes.   Ray Peat wrote an interesting article about DHEA and moles. In the linked article, he referenced dhea as something which apparently removed one of his moles. DHEA has a strong influence on retinol status, and other cofactors.

For example:

Dehydroepiandrosterone (DHEA) Sulfate Prevents Reduction in Tissue Vitamin E and Increased Lipid Peroxidation Due to Murine Retrovirus Infection of Aged Mice

 

Things that increase/stimulate DHEA production are exercise and calorie restriction.

This study was also very interesting with regards to DHEA:

Dehydroepiandrosterone Alters Retinol Status and Expression of the β-Carotene 15,15'-Monooxygenase and Lecithin:Retinol Acyltransferase Genes.

Abstract

Dehydroepiandrosterone (DHEA) and its sulfate ester DHEA-sulfate (DHEA-S) are the most abundant adrenal steroids in humans. DHEA has a critical role as a steroidal precursor of androgens and/or estrogens, and in human studies and animal experiments, both DHEA and DHEA-S have multiple beneficial effects. However, there are few reports regarding the relationship between DHEA and nutrient status, especially for vitamins. Therefore, we elucidated the effect of DHEA administration on retinol status. Wistar rats were fed with a standard diet containing 0.4% (wt/wt) DHEA for 2 wk. We assessed retinol status and the expression of retinol-related proteins, including metabolic enzymes, binding proteins, cytochrome P450 (CYP) enzymes, and antioxidant enzymes. Retinol levels in the plasma and the liver of DHEA-fed rats were lower than those of controls. Expression of β-carotene 15,15'-monooxygenase (BCMO) in the liver and intestine of DHEA-fed rats was lower, whereas BCMO expression in the testes of DHEA-fed rats was higher than that of controls. Expression of the retinol-metabolizing aldehyde dehydrogenase (ALDH) enzyme ALDH1A2 was repressed in the liver of DHEA rats, whereas ALDH1A1 expression was unaltered. Hepatic expression of lecithin:retinol acyltransferase (LRAT) and CYP26A1 was lower in DHEA-fed rats than in controls. Retinol status in DHEA-fed rats might be affected by altered BCMO expression in the liver and intestine and hepatic LRAT expression, whereas BCMO expression in peripheral tissues may be regulated in a tissue-specific manner. We have shown that DHEA administration may influence retinol status and the expression of retinol-related proteins.

 

Maybe retinol depletion modulates DHEA in the body, thus effecting moles. I'm beginning to think that skin tags and moles are actually a backup mechanism to store unwanted toxins in the body. I had a few skin tags that disappeared over the first few months, which makes me think they are also related.

Another interesting thing I observed-when I added in more vitamin A, it felt like my hormone production increased. I felt more calm, libido increased, and and my posture was straighter with little effort. There was a point while eating the liver, where i felt like you can push this too far, because I recalled my initial experience with a prothyroid and pro hormone diet.  Excessive hormone production actually will increase tension further. When I suffered from severe back pain, skin rashes, and depression, my testosterone levels were extremely high(without using any supplements. Just eating a dairy and egg based diet with no PUFAs). This lead to stiffening the muscles, skin rashes, and eventually things like unwanted body hair(which I never had before I started eating excessive amounts of dairy products), body odor, and even minor hair loss.

 

As of now, I plan to continue a high carb, moderate protein, lowish fat diet, while keeping beta carotene as low as possible. I will also keep an eye on Vitamin A. A little butter or some cheese seems to go a long way. It feels beneficial in small amounts, while higher amounts never translate to better effects. More is definitely not better with pure Vitamin A. If I crave Liver, milk, or any foods like that, I plan to have them as a one off meal, but not as a regular part of my diet. That one spoonful of chopped liver completely eliminated many cravings as well. Maybe these foods were only beneficial when they were sometimes consumed. It's easy to forget that sometimes even having a food once a month is all you need to get any benefit from it.

Hi Yh, In regards to moles I had a mole on my forearm that was picked as suspect at a skin test a couple of years ago. I decided to try the black salve as per instructions, small dab and a bandaid for two days. Some part fell of within a week and I never did any more about it. Then in the first month of low VA I thin k the same mole simply fell away. One minute it was there and the next it was like the remnant of a blister.

When I think about what is effected by VA I recall my nutrition studies years ago, skin, internal linings, eyes etc. I suspect the moles are related. Although mine was exposed it may have shifted far quicker. Let me know how yours change