Steven Bussinger
Member
There appears to be a lot of ignorance surrounding vitamin C in the Ray Peat community. I wanted to talk about my experience with it and discuss one aspect of its metabolism. First, let's talk about why this ignorance exists. It exists because of fear. This quote of Ray Peat is found in several places on the forum here:
So many people have benefited tremendously from vitamin C therapy that the scare-mongering from Ray Peat and Morley Robbins should be taken with a grain of salt. (Ascorbate salts, of course!)
Yes, this is scare-mongering. Look at the language used and the conclusion. Ray Peat clearly has his fingers up in front of his face in the form of an X. It's actually quite disappointing to see this from someone who is typically very measured in his statements and who typically admonishes the authorities for ignoring context. Oh well. We all have our blind spots and Ray Peat is no exception. He has taught us so much before that this is no reason to ignore him in the future.
Let's move on to Morley Robbins. I'm sure a handful of people here have read or heard about Morley Robbins. Perhaps they know that he is supremely against the "iron madness", that he is a huge proponent of magnesium supplementation, and that he advises against vitamin D and ascorbate supplementation. His protocols include great respect for liver and the retinol it contains, as well as an "Adrenal Cocktail" that includes OJ and cream of tartare, with no explicit disrespect for carbohydrates. So one could consider him to sit fairly close to Peat in the spectrum of health gurus. I have learned a lot from his focus on the metabolism of fat soluble vitamins and minerals.
Morley's primary contention against ascorbate supplementation is that it dysregulates copper metabolism. He believes that you should only consume the Whole Food vitamin C Complex (WFC) or else you will create a copper deficiency[1]. He cites a review that discusses several studies showing lowered copper absorption due to ascorbate supplementation.
Just a week ago, I was reading this entry of his in an effort to understand why I should be afraid of ascorbate. You see, I had come to realize that when I was supplementing with 4-5 grams of ascorbate salts a couple months ago, I was much happier. I was in much better spirits and much less irritable. Discovering more about this connection is very important to me, because this was a very significant quality of life improvement and I recently quit a good paying job in order to try a new career. So if ascorbate can lessen the anxiety of self-doubt, I am all for it.
Most of the studies in the review came to the conclusion that ascorbate lowers copper absorption. However, when the review starts to discuss copper metabolism, particularly in humans, the conclusions are less definitive. Also, the review states this:
In looking at Morley's piece, I didn't really find any suitable threads to explore. The tone of the review (written in 1998) made it quite clear that the understanding of the interactions between ascorbate and copper metabolism were still nascent and remained nebulous. Many of the studies that the review and Morley discuss are from the 1970's and 1980's. The absorption business about simultaneous ingestion of copper and ascorbate was quite settled, but there was a lot of postulating and suggesting when it came to enzyme activity. Which meant that the study findings didn't quite line up with anyone's hypothesis.
I looked for some literature on anxiety and depression and vitamin C. There are a few studies on the anxiolytic effect of vitamin C. There are also some about depression. Most say good things about vitamin C.
But then I realized something: what if the reason why ascorbate lowers anxiety and depression is because ascorbate depletes copper? In this case, Morley's still correct about copper depletion -- but it's actually a good thing for people with anxiety or depression.
One of my driving forces when I do nutrition research is the desire to reconcile seemingly contradictory theories or evidence by discovering a new context. And here was a potential example of that. If people are suffering from depression or anxiety due to an excess of copper, taking ascorbate is probably a good idea to clear that copper out. It might be contra-indicated long-term, but at least you have a new tool to use when managing your own health.
Then I searched for correlations between copper levels and depression. It wasn't hard to find studies showing that.
Morley Robbins makes a big deal out of ceruloplasmin and how important that is for copper metabolism. One of the things I've learned from him is how pivotal proteins (and enzymes) are when trying to understand the metabolism of something. If your body is not producing enough transport proteins, or interfering with them in some other way, that might be why you have a deficiency or excess of something (usually a metal like copper or iron). And looking at transport proteins also explains why you could have both an excess and a deficiency at the same time: you have lots, it's just not in the right place! Metalo-proteins are very interesting; I suggest studying them at some point (metallothionein is another one).
The next thing I looked at was if ascorbate had any effects on ceruloplasmin. This led me to a couple of papers by Edward D. Harris and Susan S. Percival.[2][3] Their studies showed that ascorbate enhanced the release of copper ions from ceruloplasmin into cells by reducing the copper ions. In a separate review[4], Harris makes this abundantly clear:
In all of the papers I just cited, the authors hypothesize that copper deficiency and scurvy are largely the same disease because they share incredibly similar symptom profiles. This makes sense in light of ascorbate's role, which is perfectly elucidated by one of the paper titles: Ascorbate Enhances Copper Transport from Ceruloplasmin into Human Cells! Ascorbate is helping ceruloplasmin in the final hand-off to the cells, so that copper can complete its job as a co-factor in a multitude of enzymatic processes.
You know how vitamin C is important for collagen cross-linking? Guess what, so is copper.
You know how vitamin C improves the endothelium/vasculature? Guess what, so does copper.
This also provides a way to understand some of the effects that vitamin C is purported to have -- primarily via Copper Zinc Oxide Dismutase (CuZnSOD). Anything from immune system improvements to diabetes.
I posit that ascorbate (when taken appropriately) will actually improve anemia. Copper supplementation has been shown to solve anemia in some cases.
I have a second part planned where I will look into another dynamic between copper and ascorbate, with a brief bit about iron. But since most people will want a recommendation after reading this, I will leave one here.
Unfortunately, we do not have very much data about the most optimal time to take ascorbate. There is just the one study looking at 75 minutes pre-food and 75 minutes post-food. Most studies have not looked at the timing of events and this is why the understanding of the copper hand-off has gone under the radar. As you can see, it actually flips Morley's hypothesis on its head! Ascorbate improves copper metabolism, regardless of whether it comes from food!
Recommendation:
The ascorbate dose 75 minutes post-food is where the increased enzyme activity took place. So perhaps an hour after a meal, when copper is freshly circulating, but before it heads to the liver for storage?
[1] Ascorbic Acid Causes Copper Deficiency?… Huh?!?…
[2] Ascorbate Enhances Copper Transport from Ceruloplasmin into Human K562 Cells
[3] A role for ascorbic acid in copper transport
[4] Copper Transport: An Overview
So many people have benefited tremendously from vitamin C therapy that the scare-mongering from Ray Peat and Morley Robbins should be taken with a grain of salt. (Ascorbate salts, of course!)
Yes, this is scare-mongering. Look at the language used and the conclusion. Ray Peat clearly has his fingers up in front of his face in the form of an X. It's actually quite disappointing to see this from someone who is typically very measured in his statements and who typically admonishes the authorities for ignoring context. Oh well. We all have our blind spots and Ray Peat is no exception. He has taught us so much before that this is no reason to ignore him in the future.
Let's move on to Morley Robbins. I'm sure a handful of people here have read or heard about Morley Robbins. Perhaps they know that he is supremely against the "iron madness", that he is a huge proponent of magnesium supplementation, and that he advises against vitamin D and ascorbate supplementation. His protocols include great respect for liver and the retinol it contains, as well as an "Adrenal Cocktail" that includes OJ and cream of tartare, with no explicit disrespect for carbohydrates. So one could consider him to sit fairly close to Peat in the spectrum of health gurus. I have learned a lot from his focus on the metabolism of fat soluble vitamins and minerals.
Morley's primary contention against ascorbate supplementation is that it dysregulates copper metabolism. He believes that you should only consume the Whole Food vitamin C Complex (WFC) or else you will create a copper deficiency[1]. He cites a review that discusses several studies showing lowered copper absorption due to ascorbate supplementation.
Just a week ago, I was reading this entry of his in an effort to understand why I should be afraid of ascorbate. You see, I had come to realize that when I was supplementing with 4-5 grams of ascorbate salts a couple months ago, I was much happier. I was in much better spirits and much less irritable. Discovering more about this connection is very important to me, because this was a very significant quality of life improvement and I recently quit a good paying job in order to try a new career. So if ascorbate can lessen the anxiety of self-doubt, I am all for it.
Most of the studies in the review came to the conclusion that ascorbate lowers copper absorption. However, when the review starts to discuss copper metabolism, particularly in humans, the conclusions are less definitive. Also, the review states this:
My eyebrow shot up at that, and I began to wonder if the case against ascorbate was not so rock solid.
In looking at Morley's piece, I didn't really find any suitable threads to explore. The tone of the review (written in 1998) made it quite clear that the understanding of the interactions between ascorbate and copper metabolism were still nascent and remained nebulous. Many of the studies that the review and Morley discuss are from the 1970's and 1980's. The absorption business about simultaneous ingestion of copper and ascorbate was quite settled, but there was a lot of postulating and suggesting when it came to enzyme activity. Which meant that the study findings didn't quite line up with anyone's hypothesis.
I looked for some literature on anxiety and depression and vitamin C. There are a few studies on the anxiolytic effect of vitamin C. There are also some about depression. Most say good things about vitamin C.
But then I realized something: what if the reason why ascorbate lowers anxiety and depression is because ascorbate depletes copper? In this case, Morley's still correct about copper depletion -- but it's actually a good thing for people with anxiety or depression.
One of my driving forces when I do nutrition research is the desire to reconcile seemingly contradictory theories or evidence by discovering a new context. And here was a potential example of that. If people are suffering from depression or anxiety due to an excess of copper, taking ascorbate is probably a good idea to clear that copper out. It might be contra-indicated long-term, but at least you have a new tool to use when managing your own health.
Then I searched for correlations between copper levels and depression. It wasn't hard to find studies showing that.
Morley Robbins makes a big deal out of ceruloplasmin and how important that is for copper metabolism. One of the things I've learned from him is how pivotal proteins (and enzymes) are when trying to understand the metabolism of something. If your body is not producing enough transport proteins, or interfering with them in some other way, that might be why you have a deficiency or excess of something (usually a metal like copper or iron). And looking at transport proteins also explains why you could have both an excess and a deficiency at the same time: you have lots, it's just not in the right place! Metalo-proteins are very interesting; I suggest studying them at some point (metallothionein is another one).
The next thing I looked at was if ascorbate had any effects on ceruloplasmin. This led me to a couple of papers by Edward D. Harris and Susan S. Percival.[2][3] Their studies showed that ascorbate enhanced the release of copper ions from ceruloplasmin into cells by reducing the copper ions. In a separate review[4], Harris makes this abundantly clear:
This is the key to understanding ascorbate's role in copper metabolism.
In all of the papers I just cited, the authors hypothesize that copper deficiency and scurvy are largely the same disease because they share incredibly similar symptom profiles. This makes sense in light of ascorbate's role, which is perfectly elucidated by one of the paper titles: Ascorbate Enhances Copper Transport from Ceruloplasmin into Human Cells! Ascorbate is helping ceruloplasmin in the final hand-off to the cells, so that copper can complete its job as a co-factor in a multitude of enzymatic processes.
You know how vitamin C is important for collagen cross-linking? Guess what, so is copper.
You know how vitamin C improves the endothelium/vasculature? Guess what, so does copper.
This also provides a way to understand some of the effects that vitamin C is purported to have -- primarily via Copper Zinc Oxide Dismutase (CuZnSOD). Anything from immune system improvements to diabetes.
I posit that ascorbate (when taken appropriately) will actually improve anemia. Copper supplementation has been shown to solve anemia in some cases.
I have a second part planned where I will look into another dynamic between copper and ascorbate, with a brief bit about iron. But since most people will want a recommendation after reading this, I will leave one here.
Unfortunately, we do not have very much data about the most optimal time to take ascorbate. There is just the one study looking at 75 minutes pre-food and 75 minutes post-food. Most studies have not looked at the timing of events and this is why the understanding of the copper hand-off has gone under the radar. As you can see, it actually flips Morley's hypothesis on its head! Ascorbate improves copper metabolism, regardless of whether it comes from food!
Recommendation:
The ascorbate dose 75 minutes post-food is where the increased enzyme activity took place. So perhaps an hour after a meal, when copper is freshly circulating, but before it heads to the liver for storage?
[1] Ascorbic Acid Causes Copper Deficiency?… Huh?!?…
[2] Ascorbate Enhances Copper Transport from Ceruloplasmin into Human K562 Cells
[3] A role for ascorbic acid in copper transport
[4] Copper Transport: An Overview
