Quote from Johannes on November 7, 2021, 9:46 am

Personally, I think the vitamin A theory is valid only because I’ve restricted retinoids from my diet for about 18 months now and observed the following effects:

• Dramatic skin improvement, with increased thickness, hydration and smoothness, less calluses and flakes; no more dry lips
• De novo hair growth on hands and feet, increased eyebrow density
• Not a single nosebleed or cold in 18 months, no real migraine (with aura)
• Increased adhesion of tooth enamel, which, strangely, I discovered after the dentist applied fluoride paste to my teeth that I really struggled to get off (brushing wasn’t enough, I had to scrape it off almost like paint); I believe this could be due to vitamin A-induced downregulation of the adhesion protein ameloblastin (AMBN), up to -30% (p < 0.05) in adipocytes, whereas expression is increased nonsignificantly by 190% in VAD rat liver
• Decreased anxiety and stress, increased self-confidence
• I want to believe that my logical reasoning and critical thinking have improved but I have no way of confirming that

On the other hand, in a scientific sense, the topic of retinoids is incredibly complex because there are so many different metabolites and isomers involved, many with completely different or opposite effects. Even if in vitro experiments appear to show that a specific retinoid has a certain effect, we can’t be sure if that effect actually occurs at physiological conditions in the body. To the best of my knowledge, the following statements seem to be accurate:

• Retinyl palmitate is not overtly toxic, it is lipogenic and potentially anti-inflammatory (by inducing biosynthesis of palmitic acid, which is an antioxidant)
• The bioavailability of beta β-carotene in fruits/vegetables is only around 20% (van het Hof, West et al. 2000); bioavailability sometimes increases with processing (such as cooking), but still this suggests that β-carotene only plays a minor role in VA toxicity (except when added in extreme amounts as a dye)
• Even though it does not get cleaved to two retinal molecules, lycopene may still be equally as or more toxic than β-carotene, since it is more fat-soluble and can be metabolized to acycloretinal and subsequently to acycloretinoic acid, which, from a chemical perspective, looks like it would have pro-inflammatory effects and has been reported to induce apoptosis (Kotake-Nara, Kim et al. 2002); autoxidation of lycopene can yield apo-12’-lycopenal, which is predicted to interact with acetyl-CoA carboxylase 2 (ACACB), the rate-limiting enzyme in fatty acid synthesis, so lycopene may be more lipogenic than other retinoids
• Lutein seems to be one of the more toxic carotenoids, since it gets cleaved to one molecule of (3R)-OH-retinal and one molecule of (3S)-OH-retinal; in the VITAL study participants supplementing with lutein had the greatest hazard ratio for getting lung cancer of all groups (Satia, Littman et al. 2009)
• Retinal is highly toxic everywhere except in the eyes, damaging DNA, proteins and membranes
• all-trans-Retinoic acid is a proto-cytokine that elicits an immune response when metabolized to (4S)-OH-RA, it also inhibits wound healing and is probably lipolytic
• (4R)-OH-RA is anti-inflammatory and possibly gets metabolized to a substance active as an estrogen, therefore I believe (4R)-OH-RA is lipogenic
• During embryogenesis, (4S)-OH-RA or possibly 9-cis-(4S)-OH-RA is metabolized to all-trans/9-cis-4-oxo-RA by CYP3A7, which is reduced back to (4S)-OH-RA; this loop is crucial for the normal development of children, but that by itself is far from enough evidence to prove that specifically exogenous retinyl palmitate is a vitamin

The discussion relating to the vitamin A content of meat is very interesting. As Jeremy noted, (Jin, Cheng et al. 2015) report 379–551 µg/100g muscle at 150 days post-intervention. One thing that stood out to me was that 20% of the feed consisted of “palm meal”, and red palm oil is known to contain very high amounts of vitamin A, about 7,000 µg retinol equivalents/100g according to one study (Loganathan, Subramaniam et al. 2017). I don’t know whether cows are normally fed palm meal, or whether palm meal actually contains red palm oil, but it’s something to be aware of.

The other study by (Darwish, Ikenaka et al. 2016) leaves out almost all of the methods, referencing the “method described previously” by (Hosotani and Kitagawa 2003), which only describes a procedure for quantifying retinol in human serum and rat liver, not in beef muscle meat. Importantly, the authors don’t mention which body part the samples are from and how they separated the muscle from fat and skin. Additionally, the fact that they don’t provide the raw results (i.e. in a table, not figure) is inconvenient.

Even though both studies aren’t of the quality we would hope for, they do raise some important questions. Most shocking in my opinion is the fact that I could’t find any other, higher quality studies apart from those discussed. We don’t even need animal studies to answer this question, the investigators could have simply gone to Arby’s and performed HPLC on some sandwich meats. Apart from that, the studies, with all their shortcomings, do seem to suggest that the vitamin A content in meat could be substantially higher than previously assumed by USDA and older studies, and it’s a shame that we don’t have any more precise data. Thus, the bioavailability of vitamin A in meat also needs to be determined, and I believe it could be lower than in vegetables because the structure of meat is more durable than that of vegetables, and the food matrix is harder to break down. On the other hand, retinyl palmitate, which makes up about 90% of liver vitamin A stores in pigs (Ayuso, Óvilo et al. 2015), is significantly more bioavailable than the carotenoids, so as usual, we are left with even more questions and not many answers.

Bibliography

Ayuso, M., C. Óvilo, A. Fernández, Y. Nuñez, B. Isabel, A. Daza, C. J. López-Bote and A. I. Rey (2015). "Effects of dietary vitamin A supplementation or restriction and its timing on retinol and α-tocopherol accumulation and gene expression in heavy pigs." Animal Feed Science and Technology 202: 62-74.

Darwish, W. S., Y. Ikenaka, A. E. Morshdy, K. I. Eldesoky, S. Nakayama, H. Mizukawa and M. Ishizuka (2016). "β-carotene and retinol contents in the meat of herbivorous ungulates with a special reference to their public health importance." The Journal of veterinary medical science 78(2): 351-354.

Hosotani, K. and M. Kitagawa (2003). "Improved simultaneous determination method of beta-carotene and retinol with saponification in human serum and rat liver." J Chromatogr B Analyt Technol Biomed Life Sci 791(1-2): 305-313.

Jin, Q., H. Cheng, F. Wan, Y. Bi, G. Liu, X. Liu, H. Zhao, W. You, Y. Liu and X. Tan (2015). "Effects of feeding β-carotene on levels of β-carotene and vitamin A in blood and tissues of beef cattle and the effects on beef quality." Meat Science 110: 293-301.

Kotake-Nara, E., S. J. Kim, M. Kobori, K. Miyashita and A. Nagao (2002). "Acyclo-retinoic acid induces apoptosis in human prostate cancer cells." Anticancer Res 22(2a): 689-695.

Loganathan, R., K. M. Subramaniam, A. K. Radhakrishnan, Y.-M. Choo and K.-T. Teng (2017). "Health-promoting effects of red palm oil: evidence from animal and human studies." Nutrition Reviews 75(2): 98-113.

Satia, J. A., A. Littman, C. G. Slatore, J. A. Galanko and E. White (2009). "Long-term Use of β-Carotene, Retinol, Lycopene, and Lutein Supplements and Lung Cancer Risk: Results From the VITamins And Lifestyle (VITAL) Study." American Journal of Epidemiology 169(7): 815-828.

van het Hof, K. H., C. E. West, J. A. Weststrate and J. G. A. J. Hautvast (2000). "Dietary Factors That Affect the Bioavailability of Carotenoids." The Journal of Nutrition 130(3): 503-506.

Quote from Armin on November 7, 2021, 10:45 am

If beef and animal meat has more Vitamin A than previously thought, does that suggest that soluble fiber is more important than previously thought as well? Cooking retinol rich foods breaks it down into retinoic acid, and without fiber to absorb the excessive oil laden RA, I can see it become a problem down the line. Maybe this is why the carnivore/keto diets eventually turn sour. Soluble fiber may aid bile excretion as well as quarantining incoming Vitamin A saturated lipids. 

Quote from Retinoicon on November 7, 2021, 11:33 am

@johannes - super interesting post. Thanks! Let me follow-up on a couple of details. 

On what palm meal is, this article is useful. It is a different "marketable product" from the African oil palm fruit than palm oil itself. Palm kernel meal is indeed used in animal feed. I could not find any information about micronutrients in palm kernel meal. I am not sure if the other "marketable product", palm oil, is the same thing as what you called "red palm oil". 

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/palm-kernel-meal

For the Jin et al study, the time path of retinol concentrations is interesting. Even if palm kernel meal ends up having tons of vitamin A in it, the time path of retinol levels is decreasing over the last three months of a five month finishing diet with palm kernel meal and the vitamin-A-containing premix. 

On the muscle being sampled in the Darwish et al study, it was the longissimus dorsi muscle for all species studied. Hopefully this muscle is interior to the animal and don't have tons of skin on it. There were 125 male animals from several species, with 20 grass-finished cattle and 20 grain-finished cattle. 

 

Quote from Armin on November 7, 2021, 11:49 am

Quote from Retinoicon on November 7, 2021, 11:33 am

 

 

On the muscle being sampled in the Darwish et al study, it was the longissimus dorsi muscle for all species studied. Hopefully this muscle is interior to the animal and don't have tons of skin on it. 

 

It appears that this muscle is a relatively superficial muscle and it runs along each side of the horse’s spine above the ribs and is one of the largest and longest muscles in your horse’s body. It’s purpose is to extend the spine . 

Quote from Retinoicon on November 7, 2021, 1:19 pm

To simplify the discussion what palm kernel meal is, it is basically a bunch of protein, not fat (as in oil). 

Quote from Даниил on November 10, 2021, 1:26 pm

@tim-2 xerophthalmia is listed in the list of side effects of accutane:

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3970835/ https://pharmru.com/product/roaccutane-capsules-10-mg-30-pcs/rophthalmia

Quote from David on December 2, 2021, 9:34 am

Quote from salt on November 2, 2021, 4:47 am

Grass fed meat definintely has significant levels of VA but I think Grant's blood tests show that despite eating grass fed meat (and red beans) his diet was still low enough to deplete VA over time, his blood VA levels still went down to almost nothing.

@salt

EDIT: You were probably talking about this thread you started about conventional and grassfed beef and you probably don't have to add anything here since you already made it in this thread:
Conventional beef vs grassfed beef - Discussion | Ideas, Concepts, and Observations (ggenereux.blog)
The values for beta-carotene in beef muscle meat that you quote in that thread is quite similar (1-74 µg/ 100 g), lower for grain feed, to the values from the 1988 study by M. Heinonen with store bought meat (22-36 µg/ 100 g).

Did you see one of my post in this thread on page 12?
Why I don’t think that this is a legit theory anymore - Page 12 - Discussion | Ideas, Concepts, and Observations (ggenereux.blog)

In one of the post I have attached a Table (attached in this post) from a 1988 study by M. Heinonen on store bought meat in Finland where they measured different forms of vitamin A. The mean beta-carotene content in different cuts of beef muscle meat varied between 22 and 34 µg /100 g of meat. According to an legacy FDA analysis, 36 µg of beta-carotene per 100 g is the same concentration as roasted hazelnuts, not a significant amount to me. FoodData Central for Hazelnuts (usda.gov)

Do you have any studies showing significant levels of carotenoids in muscle meat from beef?
-I do believe the variation in carotenoids content between different cows, different  pastures and different regions can be quite huge.

Quote from salt on December 2, 2021, 9:18 pm

Quote from David on December 2, 2021, 9:34 am

Quote from salt on November 2, 2021, 4:47 am

Grass fed meat definintely has significant levels of VA but I think Grant's blood tests show that despite eating grass fed meat (and red beans) his diet was still low enough to deplete VA over time, his blood VA levels still went down to almost nothing.

@salt

EDIT: You were probably talking about this thread you started about conventional and grassfed beef and you probably don't have to add anything here since you already made it in this thread:
Conventional beef vs grassfed beef - Discussion | Ideas, Concepts, and Observations (ggenereux.blog)
The values for beta-carotene in beef muscle meat that you quote in that thread is quite similar (1-74 µg/ 100 g), lower for grain feed, to the values from the 1988 study by M. Heinonen with store bought meat (22-36 µg/ 100 g).

Did you see one of my post in this thread on page 12?
Why I don’t think that this is a legit theory anymore - Page 12 - Discussion | Ideas, Concepts, and Observations (ggenereux.blog)

In one of the post I have attached a Table (attached in this post) from a 1988 study by M. Heinonen on store bought meat in Finland where they measured different forms of vitamin A. The mean beta-carotene content in different cuts of beef muscle meat varied between 22 and 34 µg /100 g of meat. According to an legacy FDA analysis, 36 µg of beta-carotene per 100 g is the same concentration as roasted hazelnuts, not a significant amount to me. FoodData Central for Hazelnuts (usda.gov)

Do you have any studies showing significant levels of carotenoids in muscle meat from beef?
-I do believe the variation in carotenoids content between different cows, different  pastures and different regions can be quite huge.

I think 36 µg per 100g is significant.

Yeah in that other thread I posted some studies that found an even greater amount of VA in meat, but I think the old Finnish study is probably closer to the average. Although Finnish cows probably eat quite a lot of grass, especially during summer.

Quote from David on December 3, 2021, 7:35 am

@salt

Each to their own.

EDIT: To each their own.

The consumed amount is also an important parameter as per:
(Total intake) = (Weight) x (Concentration per weight unit)

Say someone consumed 1000 g of beef muscle meat per day, which is a lot of meat. That might be around 340 mcg of beta-carotene on top of the small amount of retinol in beef (3-22 mcg/100 g), numbers from the 1988 Finnish study by M. Heinonen.
Just looking at beta-carotene and ignoring that different foods are absorbed differently, that would be like 5 grams of carrot (assuming beta-carotene concentration of ~8332 mcg/100 g). A really really small baby-carrot weighs about 5 grams according to this site and might be comparable with 1000 g of ground beef: https://farmhouseguide.com/how-much-baby-carrots-weigh/

I attach a picture from the same site showing how big a 5 g baby-carrot is.

Everyone can decide what they want to eat and feel comfortable with. I do think that the beta-carotene in some beef muscle meat products can be significant (but far from very large) if you eat large amounts of certain types of beef muscle meat.

Thank you @salt for the beta-carotene study in your other thread corroborating the beta-carotene levels measured in this 1988 study.