Karin Dee: what a fascinating study and thanks for sharing! It’s a good reminder to continue with vitamin C rich foods. I always appreciate your skillful writing style, by the way.
This is a fascinating aspect of neurobiology as the brain is metabolically demanding and has unique mechanisms for maintaining its own micronutrient environment. Vitamin C is particularly interesting because of its roles in antioxidant defense, neurotransmitter synthesis, and protection against oxidative stress, functions that may be especially important in a tissue with such high metabolic activity. As a physician-scientist, I think the most compelling question is why the brain maintains such high concentrations of certain nutrients and how those levels change with aging, metabolic disease, or neurodegeneration. The existence of specialized transport and accumulation mechanisms suggests that systemic blood levels alone may not always tell us the full story of what is happening within the brain.
At the same time, we should be careful not to assume that more is necessarily better. The challenge is understanding the relationship between nutrient status, brain homeostasis, and clinical outcomes, and determining whether supplementation benefits people who are deficient, or whether it meaningfully changes disease risk in otherwise replete individuals. That distinction is where fascinating biology meets clinically actionable science.
One of the ways I take vitamin C from food is adding organic acerola powder. One scoop has 544mg of vitamin C and I add it to my morning hydration drink.
This is a careful write-up, and I appreciate that you land on adequacy rather than megadosing.
The part I'd hold most loosely is the high-end twist. In a cohort measuring serum C once, that above-2.3 sliver is about 1 percent, and the far tail of a single measurement is exactly where reverse causation and confounding tend to masquerade as a dose-response curve, since very high levels can just flag heavy supplementers who differ in other ways. So the U-shape may be real biology or may be the tail misbehaving, and the sweet-spot reading is strongest in the middle where the data actually is.
Hello Karin! I'm new to your sub stack, and I am also apoe4/4, 37 years old, had no idea my Nutrition Genome DNA test would test for apoe4 status, but I'm so thankful I now know and can start early prevention steps.
I have following Morley Robbins root cause protocol for about 2 years now due to issues with infertility and Hashimoto's. He has done a lot of research into iron/copper homeostasis and cerloplasmin, and how magnesium, retinol and whole food vitamin C play rolls in this homeostasis. If you are interested you can find him at https://therootcauseprotocol.com/.
Morley talks about how it's not vitamin C that is the issue but rather ascorbic acid. High dose ascorbic acid causes copper and ceruloplasmin to detach. Gemini has a good summary of what happens, and why HIGH DOSE WHOLE FOOD VITAMIN C does not cause this issue.
"High-dose ascorbic acid antagonizes copper absorption and unloads copper from ceruloplasmin, reducing its oxidase activity. Whole food vitamin C is superior because it supplies the necessary bioflavonoids, enzymes, and trace cofactors that buffer absorption, prevent mineral imbalances, and ensure the nutrient works synergistically without isolating individual minerals. [1, 2, 3, 4]
The Effects of High-Dose Ascorbic Acid
• Copper Depletion: Research indicates that high supplemental intakes of ascorbic acid (often over 1,000 mg daily) inhibit the intestinal absorption of dietary copper.
• Ceruloplasmin Interference: Ascorbic acid labilizes copper bound to ceruloplasmin, temporarily lowering its levels and reducing the protein's ferroxidase activity, which is vital for iron mobilization.
• The "Ascorbic Acid" Misconception: Synthetic ascorbic acid is merely the antioxidant shell of the vitamin C complex. When taken in massive, isolated doses, it can stress mineral ratios—a fact extensively documented by the Linus Pauling Institute regarding ceruloplasmin oxidase activity.
Why Whole Food Vitamin C is Best
• The Full Complex: Whole food vitamin C (found naturally in foods like acerola cherry, amla, and citrus) is a complex of ascorbic acid, bioflavonoids (like rutin and hesperidin), tyrosinase, and other trace cofactors.
• Synergistic Absorption: The natural bioflavonoids in whole foods enhance the bioavailability of vitamin C and protect against mineral leaching.
• Optimal Utilization: Rather than causing artificial dumps of trace minerals like copper, whole food sources supply trace minerals naturally, working in harmony with your body’s enzymatic processes rather than overwhelming them. [1]
Excellent additions - Personally I like to get my Vitamin C from real food! I also have Hashimotos. Was diagnosed over 30 years ago. Check my older post about thyroid and genetics.
That is so interesting that you also have Hashimoto's. I am currently working with a functional fertility practitioner. She had me do a GI Map, Tiny Health has a more affordable one, and I have 2 strains of opportunistic bacteria which dominate my colon (Staph Aureus and Enterococcus Faecalis; I am a C-section baby so it makes sense). We are currently healing my gut. Autoimmunity has a huge gut health connection, so we'll see! 🙏
Karin Dee: what a fascinating study and thanks for sharing! It’s a good reminder to continue with vitamin C rich foods. I always appreciate your skillful writing style, by the way.
This is a fascinating aspect of neurobiology as the brain is metabolically demanding and has unique mechanisms for maintaining its own micronutrient environment. Vitamin C is particularly interesting because of its roles in antioxidant defense, neurotransmitter synthesis, and protection against oxidative stress, functions that may be especially important in a tissue with such high metabolic activity. As a physician-scientist, I think the most compelling question is why the brain maintains such high concentrations of certain nutrients and how those levels change with aging, metabolic disease, or neurodegeneration. The existence of specialized transport and accumulation mechanisms suggests that systemic blood levels alone may not always tell us the full story of what is happening within the brain.
At the same time, we should be careful not to assume that more is necessarily better. The challenge is understanding the relationship between nutrient status, brain homeostasis, and clinical outcomes, and determining whether supplementation benefits people who are deficient, or whether it meaningfully changes disease risk in otherwise replete individuals. That distinction is where fascinating biology meets clinically actionable science.
Thank you!
One of the ways I take vitamin C from food is adding organic acerola powder. One scoop has 544mg of vitamin C and I add it to my morning hydration drink.
This is a careful write-up, and I appreciate that you land on adequacy rather than megadosing.
The part I'd hold most loosely is the high-end twist. In a cohort measuring serum C once, that above-2.3 sliver is about 1 percent, and the far tail of a single measurement is exactly where reverse causation and confounding tend to masquerade as a dose-response curve, since very high levels can just flag heavy supplementers who differ in other ways. So the U-shape may be real biology or may be the tail misbehaving, and the sweet-spot reading is strongest in the middle where the data actually is.
Great share!
Hello Karin! I'm new to your sub stack, and I am also apoe4/4, 37 years old, had no idea my Nutrition Genome DNA test would test for apoe4 status, but I'm so thankful I now know and can start early prevention steps.
I have following Morley Robbins root cause protocol for about 2 years now due to issues with infertility and Hashimoto's. He has done a lot of research into iron/copper homeostasis and cerloplasmin, and how magnesium, retinol and whole food vitamin C play rolls in this homeostasis. If you are interested you can find him at https://therootcauseprotocol.com/.
Morley talks about how it's not vitamin C that is the issue but rather ascorbic acid. High dose ascorbic acid causes copper and ceruloplasmin to detach. Gemini has a good summary of what happens, and why HIGH DOSE WHOLE FOOD VITAMIN C does not cause this issue.
"High-dose ascorbic acid antagonizes copper absorption and unloads copper from ceruloplasmin, reducing its oxidase activity. Whole food vitamin C is superior because it supplies the necessary bioflavonoids, enzymes, and trace cofactors that buffer absorption, prevent mineral imbalances, and ensure the nutrient works synergistically without isolating individual minerals. [1, 2, 3, 4]
The Effects of High-Dose Ascorbic Acid
• Copper Depletion: Research indicates that high supplemental intakes of ascorbic acid (often over 1,000 mg daily) inhibit the intestinal absorption of dietary copper.
• Ceruloplasmin Interference: Ascorbic acid labilizes copper bound to ceruloplasmin, temporarily lowering its levels and reducing the protein's ferroxidase activity, which is vital for iron mobilization.
• The "Ascorbic Acid" Misconception: Synthetic ascorbic acid is merely the antioxidant shell of the vitamin C complex. When taken in massive, isolated doses, it can stress mineral ratios—a fact extensively documented by the Linus Pauling Institute regarding ceruloplasmin oxidase activity.
Why Whole Food Vitamin C is Best
• The Full Complex: Whole food vitamin C (found naturally in foods like acerola cherry, amla, and citrus) is a complex of ascorbic acid, bioflavonoids (like rutin and hesperidin), tyrosinase, and other trace cofactors.
• Synergistic Absorption: The natural bioflavonoids in whole foods enhance the bioavailability of vitamin C and protect against mineral leaching.
• Optimal Utilization: Rather than causing artificial dumps of trace minerals like copper, whole food sources supply trace minerals naturally, working in harmony with your body’s enzymatic processes rather than overwhelming them. [1]
AI responses may include mistakes."
[1] https://elivide.com/blogs/news/wholefood-vitamin-c-vs-ascorbic-acid
[2] https://www.lifeextension.com/magazine/2000/9/report_copper
[3] https://pubmed.ncbi.nlm.nih.gov/1717196/
[4] https://lpi.oregonstate.edu/mic/minerals/copper
[5] https://patient.info/features/diet-and-nutrition/vitamin-c-benefits-sources-and-deficiency
[6] https://www.researchgate.net/publication/21192575_A_role_for_ascorbic_acid_in_copper_transport
Excellent additions - Personally I like to get my Vitamin C from real food! I also have Hashimotos. Was diagnosed over 30 years ago. Check my older post about thyroid and genetics.
That is so interesting that you also have Hashimoto's. I am currently working with a functional fertility practitioner. She had me do a GI Map, Tiny Health has a more affordable one, and I have 2 strains of opportunistic bacteria which dominate my colon (Staph Aureus and Enterococcus Faecalis; I am a C-section baby so it makes sense). We are currently healing my gut. Autoimmunity has a huge gut health connection, so we'll see! 🙏
For what it’s worth. I have 3 friends who all conceived after acupuncture treatments!
Wow.. what could be more simple than taking a daily Vitamin C supplement?
Better to get Vitamin C from food!