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All Roads Lead To Anhydroretinol: The Sneaky Vitamin A metabolite that causes Vitamin A Toxicity
Quote from Tobias on March 31, 2024, 7:40 amQuote from AlexM on March 31, 2024, 4:58 amFolate plays a crucial role in DNA synthesis and repair through its involvement in one-carbon metabolism. One-carbon metabolism is a series of biochemical reactions that provide one-carbon units necessary for the synthesis of DNA precursors, such as thymidine, as well as for DNA methylation reactions.
Here's how folate contributes to DNA repair:
Thymidine Synthesis: Folate is required for the synthesis of thymidine, one of the four nucleotides that make up DNA. Thymidine is synthesized from deoxyuridine monophosphate (dUMP) in a reaction catalyzed by the enzyme thymidylate synthase. Folate provides the one-carbon units necessary for the conversion of dUMP to dTMP (deoxythymidine monophosphate). This process ensures an adequate supply of thymidine for DNA replication and repair.
Methylation Reactions: Folate is also involved in DNA methylation reactions, which play roles in gene regulation, chromatin structure, and DNA repair. Methylation involves the addition of a methyl group (CH3) to DNA, typically at cytosine bases within CpG dinucleotides, forming 5-methylcytosine. Folate provides the methyl group needed for this reaction indirectly by contributing to the synthesis of S-adenosylmethionine (SAM), which serves as a methyl donor in DNA methylation reactions.
Maintenance of Nucleotide Pools: Folate helps maintain an adequate supply of nucleotides for DNA synthesis and repair by participating in the synthesis of purines (adenine and guanine) in addition to thymidine. Purines are also essential components of DNA, and their availability is important for DNA repair processes.
I don't have an opinion on folate, but at least now I know what ChatGPT thinks.
It's not really about what anyone thinks, these biochemical processes and cycles (that folate is a part of) have been studied and proven, they are part of our biology it's a fact.
Folic acid does not occur in nature. It's more stable than other forms of folate so it's used in fortification. It was tested in rats. The problem is is that rats metabolize folic acid much more efficiently than humans and many people do not metabolize folic acid efficiently at all. When unmetabolized folic acid is chronically present in the bloodstream it promotes disease including cancer.
Folic acid fortification, like fluoride fortification is deeply problematic. It's best to minimise consumption of folic acid fortified food.
I'm not aware of any issue with natural food based folate. It's unwise to consume a low folate diet especially when chronic illness is present as nutrient recycling may be suboptimal. Low folate intake tends to increase choline requirements.
Legumes, potato, cabbage and oranges are some of the best sources of folate.
Quote from AlexM on April 1, 2024, 3:03 pm
It's not really about what anyone thinks, these biochemical processes and cycles (that folate is a part of) have been studied and proven, they are part of our biology it's a fact.
The conclusions mainstream academics draw from these processes are not fact, they're conjecture and I highly encourage you to do your own research. Here's an excellent paper providing an overview of our current understanding and the gaps in our knowledge of folate. Copy pasting ChatGPT is intellectually lazy and I don't want to see it become the norm.
Quote from Tobias on April 2, 2024, 6:38 amQuote from AlexM on April 1, 2024, 3:03 pmIt's not really about what anyone thinks, these biochemical processes and cycles (that folate is a part of) have been studied and proven, they are part of our biology it's a fact.
The conclusions mainstream academics draw from these processes are not fact, they're conjecture and I highly encourage you to do your own research. Here's an excellent paper providing an overview of our current understanding and the gaps in our knowledge of folate. Copy pasting ChatGPT is intellectually lazy and I don't want to see it become the norm.
@tobias Wrong. You are playing devils advocate here, the things that were in my post such as Thymidine Synthesis, Methylation Reactions and the role folate plays in them are well indeed scientific facts. The biochemical pathways have been mapped out for those processes and folate is a vital part of them. Not really sure why you mention "conclusions" there are no conclusions in the things that were mentioned in my post but rather scientific facts rooted in decades of scientific inquiry and experimentation. You admit those biochemical processes exist in your post, so you are already agreeing with the information in my post inadvertently, as those parts mentioned in my post were simply just explaining folate's role in those processes.
Maybe try and ask the authors of the paper you linked or some biochemists if those things in my post are conjecture rather than facts and they will tell you otherwise.
@jessica2
Off the top of my head I think poor folic acid metabolism can also often be acquired. Presumably due to declining liver function.
IMO it's best for everyone to avoid supplements containing pyridoxine or folic acid. A B complex should contain P5P and folate instead.
I think a good policy with regard to folic acid fortified bread is to avoid having it at home but not worrying about it when out.
Quote from AlexM on April 2, 2024, 2:20 pmQuote from Tobias on April 2, 2024, 6:38 amQuote from AlexM on April 1, 2024, 3:03 pmIt's not really about what anyone thinks, these biochemical processes and cycles (that folate is a part of) have been studied and proven, they are part of our biology it's a fact.
The conclusions mainstream academics draw from these processes are not fact, they're conjecture and I highly encourage you to do your own research. Here's an excellent paper providing an overview of our current understanding and the gaps in our knowledge of folate. Copy pasting ChatGPT is intellectually lazy and I don't want to see it become the norm.
@tobias Wrong. You are playing devils advocate here, the things that were in my post such as Thymidine Synthesis, Methylation Reactions and the role folate plays in them are well indeed scientific facts. The biochemical pathways have been mapped out for those processes and folate is a vital part of them. Not really sure why you mention "conclusions" there are no conclusions in the things that were mentioned in my post but rather scientific facts rooted in decades of scientific inquiry and experimentation. You admit those biochemical processes exist in your post, so you are already agreeing with the information in my post inadvertently, as those parts mentioned in my post were simply just explaining folate's role in those processes.
Maybe try and ask the authors of the paper you linked or some biochemists if those things in my post are conjecture rather than facts and they will tell you otherwise.
Hi Alex @alexm
I aim to address each aspect of your argument individually.
- Your assertion that the mechanisms of folate are "final" and fully understood contradicts your engagement on this forum.
Your viewpoint on the sanctity and finality of ChatGPT's explanations, what I would call "word salad," contradicts your presence and participation on this forum. Your conceptual rationale for rejecting folate as a potential toxin mirrors precisely the mindset of individuals who refuse to recognize the toxicity of Vitamin A. If the metabolic and enzyme pathways of "Vitamin A" were genuinely undeniable facts, you would have no motive to participate in this forum, and certainly, you wouldn't subscribe to the belief that it is toxic. It's evident that you don't consider these Vitamin A pathways to be factual; otherwise, you wouldn't be present here.
- Relying on mechanistic studies as absolute truth holds little relevance in reality. Surrendering your intellectual autonomy to intellectual authorities is a guaranteed path to illness. The fervent adherence to mechanistic studies and those who treat them as infallible gospel are significant contributors to the deteriorating state of global health.
David Sinclair is often celebrated as a beacon in anti-aging science, yet physically he appears like an average person his age, albeit with a noticeable amount of Botox. It remains uncertain whether he truly consumes the myriad of plant poisons he promotes. What's evident is that he serves as a prime example of "lipstick on a pig."
David Sinclair may craft elaborate intellectual landscapes with intricate details about sirtuin genes, NFR2, and epigenetic expression, but where have these maps (similar to the ones you posted) led him and his followers? Nowhere. Despite the extensive theoretical framework, he appears like any other individual his age. In fact, many of my friends his age boast a more vibrant appearance, appearing more androgenic and robust. While in theory, one might expect him to appear significantly younger, in reality, there's nothing particularly remarkable about his appearance. Despite purportedly having all the answers, he doesn't quite reflect it in his appearance. Has he genuinely assisted ANYONE in overcoming a chronic illness or slowing down the aging process? Possibly, but I doubt it.
Countless scholars will endlessly bemoan some obscure pathway or elusive receptor for years on end. Ivy League researchers frequently indulge in intellectual self-congratulation, inhabiting a microcosm dedicated to intellectual circle-jerking.
These mechanistic test tube studies are nearly useless at worst and offer subtle clues at best. If one understood the process by which they develop these maps in scientific inquiry—using dyes, adjuvants, enzymes, and provocation methods on isolated cells to map pathways—one would likely scoff at its absurdity. This entire faction of academia amounts to little more than egoic self-indulgence. Billions of dollars have been spent and hundreds of thousands of hours invested in "mapping pathways" to develop novel drugs, only to find that they often fail to address pathological states adequately or are inferior to herbal alternatives. It's folly to place too much trust in human understanding, as we don't truly comprehend the workings of the majority of things; our knowledge is speculative at best. Most of these enzymatic pathway maps do not originate at the genesis level; rather, they are attempts at reverse engineering based on observed health outcomes.
For instance, researchers observed that fasting or calorie restriction extended the lifespan in animal models. This observation subsequently served as the basis for reverse engineering pathways to provide an explanation. Essentially, these theoretical mapped pathways relied on validating an initial observation. Do you truly grasp what this signifies? Do you comprehend the bias this introduces into science? Likewise, if Vitamin A is deemed essential, these pathways must be reverse-engineered based on this hypothesis. Otherwise, entirely new pathways and deciphering would have been drawn had Vitamin A essentiality never been claimed.
These mechanistic studies represent humanity's endeavor to feign control and understanding of the terror and pain of existence. It's akin to claiming godlike authority, yet in truth, the pursuit to transcend our infantile understanding is never fully realized.
This simplistic intellectual confidence is especially evident in discussions about the microbiome, where many individuals claim to understand more than they actually do, despite their knowledge being just a drop in the vast ocean of complexity. In reality, our understanding of the vast array of billions of microorganisms is primitive. Anyone or any group that claims otherwise is being dishonest. Microbiome and stool tests are inadequate diagnostic indicators. Ludicrously inadequate.
This brings me back to a fundamental notion: idolizing these egomaniacs contradicts your innate powers of observation. Regardless of what an epigenetic or telomere test might indicate about their biological age, they lack a true understanding of how to accurately measure it. The existing tests again are, at best, mere clues.
- Beyond mechanistic studies and data, folate has little evidence in the “real world.”
Folate is essentially ineffective for any pathological state, although mechanistically it makes methylation work gooder (lol). Mentioning the reduction of homocysteine levels is futile, as some sources suggest it may actually increase them. Similarly, discussing anemia is pointless, as conflicting opinions exist regarding its causative role. Folate cannot simultaneously cause and alleviate anemia, just as it cannot simultaneously cause and alleviate nerve problems. Psychological well-being studies are irrelevant since they often fail to measure cognitive performance. For example, fluoride and alcohol enhance psychological well-being by way of being neurological toxins. Similarly, cognitive performance studies offer data correlations that are far-fetched and absurd. So far fetched and absurd that it actually makes me wonder if I am already dead and in hell. I have thoroughly examined more than 20+ folate studies, meticulously analyzing each line, along with others of broader scope. Feel free to present a counterargument if you wish, but dismissing my understanding as lacking simply because you're impressed by ChatGPT's use of complex intellectual terms like "Thymidine Synthesis" and "Nucleotide Pools" seems odd.
- Personal and community experiences and testimonials hold greater sway than mechanistic studies and theoretical models. Despite this being common sense, many dismiss n=1 experiments as unscientific.
“True knowledge can only be ‘remembered’... Man’s knowledge cannot be greater or smaller than he is. A man ‘knows’ what he ‘is’ and never the other way around. To know means, above all else, to be...The more you are, the more you know.» There is nothing you can add to that which you already know... True knowledge cannot be acquired, it can only be ‘re-membered’."
This passage from one of my favorite books highlights the idea that genuine knowledge stems from experience, not merely intellectual understanding. No matter how elaborate scientific or literary analyses may be, they cannot surpass the depth of experiential knowledge. While many may favor mechanistic studies, I am drawn to real-world experiences and personal testimonials. Intellectualism can certainly provide insights and guidance, but true knowledge is rooted in experiential understanding—such as feeling an overwhelming passion for life or recalling the vibrant vitality experienced in simply being alive, feeling the power of one's body, and more.
Observing which pathways activate in a yeast cell when stimulated by a substance has limited relevance to real-world comprehension and application.
- Summary: Believe what you want. Consume folate (in any form) if you want. However, I would encourage you to look at the REAL data observed by real individuals across the world and echoed in every informational outlet. Then come to your own conclusions.
You haven't presented any refutation of known folate science. You're just attacking it.
"Your conceptual rationale for rejecting folate as a potential toxin mirrors precisely the mindset of individuals who refuse to recognize the toxicity of Vitamin A. If the metabolic and enzyme pathways of "Vitamin A" were genuinely undeniable facts, you would have no motive to participate in this forum, and certainly, you wouldn't subscribe to the belief that it is toxic. It's evident that you don't consider these Vitamin A pathways to be factual; otherwise, you wouldn't be present here."
"All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison." -- Paracelsus
I recognize the toxicity of excess vitamin A and I recognize that what represents excess may be a lot lower than is generally recognized but I also recognize vitamin A's essentiality. Nobody has refuted the essentiality of vitamin A.
Quote from AlexM on April 2, 2024, 2:20 pm
@tobias Wrong. You are playing devils advocate here, the things that were in my post such as Thymidine Synthesis, Methylation Reactions and the role folate plays in them are well indeed scientific facts. The biochemical pathways have been mapped out for those processes and folate is a vital part of them. Not really sure why you mention "conclusions" there are no conclusions in the things that were mentioned in my post but rather scientific facts rooted in decades of scientific inquiry and experimentation. You admit those biochemical processes exist in your post, so you are already agreeing with the information in my post inadvertently, as those parts mentioned in my post were simply just explaining folate's role in those processes.
Maybe try and ask the authors of the paper you linked or some biochemists if those things in my post are conjecture rather than facts and they will tell you otherwise.
But there are conclusions in your post, perhaps if you wrote it yourself instead of copy pasting ChatGPT you'd recognize it. I somehow doubt that I'd reach the same conclusions were I to study these processes in-depth on account of all our science being conjecture per definition and holds a poor track record of being concordant with reality. What biochemists and authors of scientific papers think is irrelevant, as science operates on logic, not authority.
And no, I'm not playing devil's advocate, I'm calling out blatant displays of scientism when I see it. You are substituting understanding with memorization, and can't even be bothered memorizing.
Quote from Luke on April 2, 2024, 7:51 pmIf the metabolic and enzyme pathways of "Vitamin A" were genuinely undeniable facts, you would have no motive to participate in this forum, and certainly, you wouldn't subscribe to the belief that it is toxic. It's evident that you don't consider these Vitamin A pathways to be factual; otherwise, you wouldn't be present here.
I'm not sure, but doesn't seem like he believes vitamin A is toxic as he is taking a parapack supplement:
Vitamin A (as palmitate and 50% as beta carotene) 2000 IU
Vitamin C (as ascorbic acid) 60 mg
Vitamin E (as d-alpha tocopheryl succinate) 30 IU
Thiamine (as thiamine hydrochloride) 1.5 mg
Niacin (as niacinamide and 33% as niacin) 20 mg
Vitamin B6 (as pyridoxine hydrochloride) 2 mg
Folic Acid (as (6S)-5-methyltetrahydrofolic acid) 25 mcg
Biotin 75 mcg
Pantothenic Acid (as d-calcium pantothenate) 10 mg
Iodine (from kelp) 100 mcg
Zinc (TRAACS® zinc bisglycinate chelate†) 1 mg
Selenium (as L-selenomethionine) 20 mcg
Manganese (TRAACS® manganese bisglycinate chelate†) 1 mg
Potassium (from potassium gluconate and 50% as potassium glycinate complex) 10 mg
Citrus Bioflavonoid Complex (citrus aurantium L.) 50mg
Inositol 25 mg
Betaine (from betaine hydrochloride) 20 mg
L-Tyrosine 10 mg
L-lysine HCL 10 mg
L-Glutamic Acid 10 mg
L-Serine 5 mg
Pyruvate (from calcium pyruvate) 5 mg *
Whole Adrenal Glandular (bovine) 5 mg *
Whole Pituitary Glandular (bovine) 5 mg *
Whole Parotid Glandular (bovine) 5 mg *