Vitamin C

[Ella]

@Janelle525 yes I am well aware of the fruit and their juices, however fruits come with a suite of other protective phytochemicals, many of which we are yet to discover.

You missed my point. All analytical methods have to align themselves or have detection levels better than toxicological standards along with other food standards. In this case the detection level should be or better than 200 ppm.

 

[InChristAlone]

@Janelle525 yes I am well aware of the fruit and their juices, however fruits come with a suite of other protective phytochemicals, many of which we are yet to discover.

You missed my point. All analytical methods have to align themselves or have detection levels better than toxicological standards along with other food standards. In this case the detection level should be or better than 200 ppm.

Yes I understand I was just focusing on how very little methanol it actually is. Especially when compared to bottled juices or other items people may come into contact with. I do agree with you that her COA really kinda sucks. I am not wedded to her product. Just that I did use it for 2 yrs now without any reaction so I'm thinking the actual numbers of a few of the listed things are much lower.

 

[Amazoniac]

It's tough to find detailed information on absorption, I was trying to do a learning on where most of it is absorbed. I don't know if they're using ascorbic acid and ascorbate interchgenagelby in some of these, but for now I'll assume the a major part of the vitamin when ingested as ascorbic acid and without excess is absorbed in the upper intestines. I also don't know the reason why it takes 2 hours to reach blood peak and if during this time it has already been cleared from the lumen of the intestines.

Ascorbic acid absorption in man - Pharmacokinetic implications

"Ascorbic acid has been shown to be taken up rapidly by the proximal intestine in man (Nicholson and Chornock, 1942) at relatively small doses (ca. 600 mg)."​

Absorption, transport, and disposition of ascorbic acid in humans - Chemistry, Metabolism, and Uses

"Ascorbate in the reduced form constitutes the majority (80–90%) of this vitamin in food.[96,97] Studies utilizing sections of human ileum[24,98] determined that ascorbate is absorbed in the human intestine by a [Na+]-dependent active transport system. Absorption is most effective in the proximal intestine.[99] Absorption of ascorbate in proximal intestine was studied directly in human subjects using intestinal perfusion to measure uptake rates, and the calculated maximal transport rate was 50 mg/cm-hr.[100] The Km was expressed as 5 mmols, indicating that the calculation may be incorrect because of an unclear effect of volume. Results of other uptake studies vary considerably,[99,101–103] perhaps as a consequence of assay imprecision or variations in subject repletion status and dose. These studies are also problematic because they used the indirect measure of urinary output as the criteria for ascorbate uptake."​

Intestinal absorption in health and disease: micronutrients (!)

"Vitamin C (ascorbic acid) is found almost exclusively in foods of plant origin. Its absorption in humans occurs in the buccal mucosa, stomach and small intestine. Buccal absorption is thought to be by way of passive diffusion through the membrane of the buccal mucosal cells. Gastrointestinal absorption of the vitamin is rapid and efficient, and an active carrier-mediated transport system has been suggested, especially at low concentrations. This active absorption mechanism becomes saturated when the mucosal concentration of vitamin C is greater than 6 mmol/l. This may account for the fact that the proportion of dietary vitamin C absorbed decreases with an increasing intake of the vitamin.[33] However, in species with no dietary requirement for vitamin C, such as rats and hamsters, the mode of intestinal absorption of the vitamin has been demonstrated to be passive transport. Prior to absorption, ascorbic acid is first oxidized to dehydroascorbate, which is then absorbed by passive diffusion or by way of glucose transporters. This may be due to the fact that, unlike ascorbic acid, the dehydroascorbate is less ionized at physiological pH and that it has marked membranepenetrating power. However, within the intestinal cell dehydroascorbate is rapidly reduced back to ascorbic acid by the enzyme dehydroascorbate reductase, which requires reduced glutathione.

The rate of absorption of ascorbic acid decreases with its increased intake. Absorption can vary from 16% at high (.10 g) to 98% at low (.20 mg) intakes. From what is known, 80–90% of the dietary ascorbic acid is absorbed.[34] Maximal ascorbic acid absorption can be achieved by the ingestion of several spaced doses of less than 1000 mg throughout the day rather than through ingestion of a single dose, by administration with meals, or by inclusion of the supplement in high-fat meals.[35] The dose-dependent intestinal absorption may be caused by a number of possible mechanisms[36]: (a) an excess of ascorbic acid may undergo degradation to carbon dioxide, which is expired in the breath; (b) the unabsorbed ascorbic acid in the intestine may result in osmotic diarrhoea and hence its absorption may be affected; and (c) the renal action to conserve or excrete ascorbic acid. The absorbed vitamin readily equilibrates with the body pool of ascorbic acid. Healthy adult men receiving adequate intakes of the vitamin have a body pool of approximately 1500 mg of ascorbic acid.[37] The excretion of ascorbic acid in the urine declines to undetectable levels with inadequate intakes of the vitamin. Because of the limited intestinal absorption of the vitamin—and its renal threshold being approximately 0.8 mg/dl plasma, it is difficult to exceed plasma levels above 1 mg/dl with high doses of ascorbic acid.

Ascorbic acid is susceptible to oxidation to dehydroascorbate, which is irreversibly degraded further by hydrolytic opening of the lactone ring; this may affect its bioavailability. The rate of oxidation is enhanced in the presence of factors such as alkali, heat, light and the mineral copper. Thus, addition of baking soda to vegetables, excessive cooking, storage at room temperature or contamination with copper (from cooking utensils), will all promote oxidation of ascorbic acid. Other factors that may affect bioavailability of ascorbic acid by impeding its intestinal absorption include excessive intakes of pectin, zinc and alcohol[34], although the mechanism of action has not yet been determined. Excessive iron concentration in the gastrointestinal tract, if present with ascorbic acid, may also result in the oxidative destruction of the vitamin.

Following absorption, ascorbic acid rapidly equilibrates in intra- and extracellular compartments. Although no particular organ acts as a storage reservoir for the vitamin, tissues such as the pituitary and adrenal glands, eye lens and leukocytes are concentrators of ascorbic acid. Ascorbic acid exists in blood and tissues mainly in its reduced form; its oxidized form is generally less than 10%. The average half-life of the vitamin in an adult human is about 20 days, with a turnover of 1 mg/kg/day and a total body pool size of 1500 mg.[38]"​

Vitamin C in Health and Disease: Its Role in the Metabolism of Cells and Redox State in the Brain

"Both ascorbate and DHA can enter enterocytes via SVCT and GLUT transporters, respectively. The absorption pattern of ascorbate is opposite to that of glucose as ascorbate is better absorbed in the most distal segments (ileum) of the small intestine and, in smaller quantities, in the most proximal segments (duodenum). For its part, DHA is better absorbed in the jejunum while very little is absorbed in the distal segments of the ileum (Malo and Wilson, 2000)."

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[InChristAlone]

So yesterday and today I greatly reduced my AA to 1-2 g. Today I only took 1 g in the morning and by the end of today I was having some free floating anxiety not connected to any stress. I realized I probably still need AA and took a couple grams and felt much better. I can't say for sure but a large dose seems to last me a long time. I don't necessarily agree with the charts but I will continue experimenting.

 

[Amazoniac]

greatly

There's something shinny there, looks like a hook beneath <tilting head>, not sure. From distance I can smell metal. I'm poking it right now and waiting for a reaction that it's safe for me to go for it.

If a single dose is all you take and you're susceptible to stress, higher amounts will be better for providing you more to deal with it during the day regardless of your skin color.

Vitamin C Supplementation Attenuates the Increases in Circulating Cortisol, Adrenaline and Anti-Inflammatory Polypeptides Following Ultramarathon Running
"The study demonstrates an attenuation, albeit transient, of both the adrenal stress hormone and anti-inflammatory polypeptide response to prolonged exercise in runners who supplemented with 1500 mg vitamin C per day when compared to ≤ 500 mg per day."​

But taking it only one time is not what we've been proposing. The appearance of anxiety only later is consistent with its effects wearing off. 8 grams at a time are likely not providing you more than 2 grams after absorption (even if you tolerate 2.5 times more than the average), probably 1.5 grams or so; and 4x 600 mg could provide you more than that. Of course it varies, but you get the idea.

There's also the adaptation aspect that was commented various times. If your body becomes used to a high intake of certain vitamins, irrespective if it's being beneficial or not, when there's a sharp change in habits the body might protest and take a while to adjust.

If you only feel better with single large doses, then I would stick to them. We've speculated about some possibilities but there can be others as well that your intuition is way gooder at picking.


- Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial

"Ascorbic acid can modulate catecholaminergic activity and decrease stress reactions (Aburawi and others, 2014)."​

- Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders? (6.2)

"The growing evidence, which has been recently emerged, suggests that anxiety is associated with Vit C deficit, whereas Vit C supplementation could help reduce feeling of anxiety. The underlying mechanism is not fully understood yet, but Vit C seems to play this role by: regulating neurotransmitters’ activity, attenuating cortisol activity, preventing stress-induced oxidative damage and antioxidant defense in brain or some as yet undetermined effects on anxiety-related brain structures [181]."

"[Researchers] examined the effect of Vit C treatment with three doses (61, 114 or 160 mg/kg/day in drinking water, 8 weeks) [in mice that can't synthesize vit C] and observed that an anxiolytic effects of Vit C were displayed in higher frequencies of walking (with doses of 114 mg/kg/day and 160 mg/kg/day), higher frequencies of rearing (with dose of 61 mg/kg/day) and lower frequencies of grooming (with dose of 61 mg/kg/day) in the open-field as well as more frequent occupation of the open arms in the elevated plus-maze (with dose of 61 mg/kg/day). The authors concluded that anxiolytic effects of Vit C were more typical of the lowest dose and it was to some extent dependent on anxiety intensity [185]."

"Gautam et al. [171] observed that patients with generalized anxiety disorder had significantly lower Vit C levels in comparison with healthy controls, whereas 6-week vitamins supplementation (vitamin C accompanied with A and E) led to a significant reduction in anxiety scores [171]."

"Mazloom et al. [190], in turn, showed that short-term supplementation of Vit C (1000 mg/day) reduced anxiety levels (evaluated basing on Depression Anxiety Stress Scales 21-item) in diabetic patients. This effect was exerted through alleviating oxidative damage. Furthermore, recently performed a systematic review also showed that high-dose Vit C supplementation was effective in reducing anxiety as well as stress-induced blood pressure increase [191]."

[191] is a review and will lead you to this:
A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress (3x 1 g per day)​

--
- Ascorbic acid: A therapeutic viability in anxiety disorders
- Effects of ascorbic acid on anxiety state and affect in a non‑clinical sample
- Inhibitory effect of ascorbic acid (vitamin C) on cortisol secretion following adrenal stimulation in children

- Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review
- N-Acetylcysteine Reverses Anxiety and Oxidative Damage Induced by Unpredictable Chronic Stress in Zebrafish

 

[Logan-]

Institute of Medicine (2000). "Vitamin C". Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C.: The National Academies Press. pp. 95–185.

 

[InChristAlone]

There's something shinny there, looks like a hook beneath <tilting head>, not sure. From distance I can smell metal. I'm poking it right now and waiting for a reaction that it's safe for me to go for it.

If a single dose is all you take and you're susceptible to stress, higher amounts will be better for providing you more to deal with it during the day regardless of your skin color.

Vitamin C Supplementation Attenuates the Increases in Circulating Cortisol, Adrenaline and Anti-Inflammatory Polypeptides Following Ultramarathon Running
"The study demonstrates an attenuation, albeit transient, of both the adrenal stress hormone and anti-inflammatory polypeptide response to prolonged exercise in runners who supplemented with 1500 mg vitamin C per day when compared to ≤ 500 mg per day."​

But taking it only one time is not what we've been proposing. The appearance of anxiety only later is consistent with its effects wearing off. 8 grams at a time are likely not providing you more than 2 grams after absorption (even if you tolerate 2.5 times more than the average), probably 1.5 grams or so; and 4x 600 mg could provide you more than that. Of course it varies, but you get the idea.

There's also the adaptation aspect that was commented various times. If your body becomes used to a high intake of certain vitamins, irrespective if it's being beneficial or not, when there's a sharp change in habits the body might protest and take a while to adjust.

If you only feel better with single large doses, then I would stick to them. We've speculated about some possibilities but there can be others as well that your intuition is way gooder at picking.


- Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial

"Ascorbic acid can modulate catecholaminergic activity and decrease stress reactions (Aburawi and others, 2014)."​

- Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders? (6.2)

"The growing evidence, which has been recently emerged, suggests that anxiety is associated with Vit C deficit, whereas Vit C supplementation could help reduce feeling of anxiety. The underlying mechanism is not fully understood yet, but Vit C seems to play this role by: regulating neurotransmitters’ activity, attenuating cortisol activity, preventing stress-induced oxidative damage and antioxidant defense in brain or some as yet undetermined effects on anxiety-related brain structures [181]."

"[Researchers] examined the effect of Vit C treatment with three doses (61, 114 or 160 mg/kg/day in drinking water, 8 weeks) [in mice that can't synthesize vit C] and observed that an anxiolytic effects of Vit C were displayed in higher frequencies of walking (with doses of 114 mg/kg/day and 160 mg/kg/day), higher frequencies of rearing (with dose of 61 mg/kg/day) and lower frequencies of grooming (with dose of 61 mg/kg/day) in the open-field as well as more frequent occupation of the open arms in the elevated plus-maze (with dose of 61 mg/kg/day). The authors concluded that anxiolytic effects of Vit C were more typical of the lowest dose and it was to some extent dependent on anxiety intensity [185]."

"Gautam et al. [171] observed that patients with generalized anxiety disorder had significantly lower Vit C levels in comparison with healthy controls, whereas 6-week vitamins supplementation (vitamin C accompanied with A and E) led to a significant reduction in anxiety scores [171]."

"Mazloom et al. [190], in turn, showed that short-term supplementation of Vit C (1000 mg/day) reduced anxiety levels (evaluated basing on Depression Anxiety Stress Scales 21-item) in diabetic patients. This effect was exerted through alleviating oxidative damage. Furthermore, recently performed a systematic review also showed that high-dose Vit C supplementation was effective in reducing anxiety as well as stress-induced blood pressure increase [191]."

[191] is a review and will lead you to this:
A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress (3x 1 g per day)​

--
- Ascorbic acid: A therapeutic viability in anxiety disorders
- Effects of ascorbic acid on anxiety state and affect in a non‑clinical sample
- Inhibitory effect of ascorbic acid (vitamin C) on cortisol secretion following adrenal stimulation in children

- Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review
- N-Acetylcysteine Reverses Anxiety and Oxidative Damage Induced by Unpredictable Chronic Stress in Zebrafish

Thanks for your analysis. I do realize that if I were to change my dosage it might take some time to adjust. I experienced this when going off cypro. Had to deal with a couple weeks of increased anxiety. But with niacinamide I went off the 100mg pretty easily didn't really notice a difference. Probably because I had the vitamin C to rely on. I know something is screwy in my brain otherwise I wouldn't have had panic disorder and to me it wasn't even a disorder when it started, it wasn't connected to irrational fears even though I did fear another one happening. I figured out certain things not to eat like refried beans and dried mangoes- my nemesis. I thought maybe it was the serotonin being produced in my gut. But many authorities claim panic is a lack of serotonin. Whereas general anxiety is too much serotonin. I definitely don't have panic anymore so maybe now it is just the serotonin aspect. And can get worse in the darkness of winter. If it is oxidative stress not sure what else to do about that.

If all it takes is using vitamin C I will continue! Much safer than drugs. Not sure if I will try NAC being Peat is not a fan of cysteine.

ETA: it could also just be low progesterone. Vitamin C has been shown to boost progesterone which isn't surprising since it supports adrenals.

 

[yerrag]

Not sure if I will try NAC being Peat is not a fan of cysteine.

Isn't NAC a precursor to glutathione? According to the following video by Chris Masterjohn, glutathione recycles oxidized vitamin C :



(this video is part of Chris' series on antioxidants, which Amazoniac shared earlier on the thread, https://chrismasterjohnphd.com/the-antioxidant-system/ . It's a good series and I'm not halfway through it yet).

Video also shows vitamin C recycling vitamin E, a fat-soluble antioxidant which readily gets past the cell membrane. Vitamin E, inside the cell, interfaces with Vitamin C, outside the cell, through the porous membrane.

If this is what's really going on, why don't we dispense with efforts on making vitamin C get into the inner cell via so many means - using the SVCT and GLUT transporter, using liposomal C, etc? Why not use Vitamin E together with Vitamin C with NAC?

The part I don't get get though is the video shows glutathione being extracellular. So maybe NAC is not effective then in this context, as NAC is a precursor to internal glutathione, as I understand it. Maybe what's needed is glutathione instead, as glutathione supplements provide for extracellular glutathione.

 

[yerrag]

There can be contaminants in water or adhered to the walls of the bottle that can speed up its degradation. You might be able to holy those, but impurities in the acid itself or the salt used might be enough to degrade part of it in less than one day. Adding bicarbonates to the solution will make it alkaline and decrease stability. I think your best bet is carrying the powder with you in a vial or something.

What if I dissolve ascorbic acid in sufficiently concentrated lime or lemon juice (enough to keep AA stable) and then when I want to take it, I add magnesium carbonate or potassium carbonate or sodium bicarbonate (baking soda) to convert the citric acid to citrate, before ingesting it?

 

[yerrag]

What if I dissolve ascorbic acid in sufficiently concentrated lime or lemon juice (enough to keep AA stable) and then when I want to take it, I add magnesium carbonate or potassium carbonate or sodium bicarbonate (baking soda) to convert the citric acid to citrate, before ingesting it?

Been reading up on zeta potential @Sheila and I was glad I did. I'd mix potassium bicarbonate with my sour orange (or lime or lemon juice, any sour citrus fruit, even our local calamansi) and keep it refrigerated, and when I need to take ascorbic acid, I'll mix the ascorbic acid with the mixture. This way, I ensure citric acid is converted to citrate (the sourness is practically gone), I don't deal with the lead contaminants with industrial citric acid, I get potassium ascorbate (Pantellini discovered how good it is against cancer), and fresh un-degraded ascorbic acid. And also I get potassium citrate (for the zeta potential benefits to decoagulate blood, and maybe helpful for hypertension).

 

[Amazoniac]

What if I dissolve ascorbic acid in sufficiently concentrated lime or lemon juice (enough to keep AA stable) and then when I want to take it, I add magnesium carbonate or potassium carbonate or sodium bicarbonate (baking soda) to convert the citric acid to citrate, before ingesting it?

Been reading up on zeta potential @Sheila and I was glad I did. I'd mix potassium bicarbonate with my sour orange (or lime or lemon juice, any sour citrus fruit, even our local calamansi) and keep it refrigerated, and when I need to take ascorbic acid, I'll mix the ascorbic acid with the mixture. This way, I ensure citric acid is converted to citrate (the sourness is practically gone), I don't deal with the lead contaminants with industrial citric acid, I get potassium ascorbate (Pantellini discovered how good it is against cancer), and fresh un-degraded ascorbic acid. And also I get potassium citrate (for the zeta potential benefits to decoagulate blood, and maybe helpful for hypertension).

I didn't miss the message. I thought at first that carrying it around ready to drink was something to avoid judicial looks from people, but then you commented about adding bicarbonate later, so it couldn't be that. It makes no sense not to leave ascorbic acid for later as well.

Isn't it interesting that in extreme stress the body admits way more vit C? But this means that it's capable of absorbing more and has the flexibility to do so if it needs. When the conditions are relatively normal, a lower absorption is then a matter of choice.

Another point that is worth mentioning is that as kidney function becomes impaired, the clearance of vit C decreases and people have higher circulating levels for the same dose, also remaining elevated for longer.
The percentages are for how the kidneys are functioning. 100% being fine and serving as reference:

Pharmacokinetic perspectives on megadoses of ascorbic acid

Above: lower doses
Below: higher doses

"Renal function is of little concern when one takes doses at or near the RDA for ascorbic acid because renal excretion contributes negligibly to overall elimination at this dose. This likely explains why we found no reported studies on the han dung of ascorbic acid in subjects with severely compromised renal function. However, the issue of renal function becomes more important when megadoses [considered as 10x the current RDA] of ascorbic acid are taken because renal excretion then becomes a more significant elimination pathway."​

There you have one more reason not to go over the board with massive doses and favor lower ones at a time. It makes us wonder: is it desirable to try to push plasma levels higher and higher with unphysiological amounts?

 

[Amazoniac]

- Vitamin C deficiency: more than just a nutritional disorder (!)

- First bioarchaeological evidence of probable scurvy in Southeast Asia: Multifactorial etiologies of vitamin C deficiency in a tropical environment (!)

- Old Disease, New Look? A First Report of Parkinsonism Due to Scurvy, and of Refeeding-Induced Worsening of Scurvy

"The activity of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, requires adequate amounts of vitamin C.5 The same is true for dopamine-hydroxylase, which converts dopamine into noradrenaline. Vitamin C also regulates the post-synaptic effects of dopamine and glutamate and is a centrally-active antioxidant."

"Vitamin C is co-released with glutamate by glutamatergic neurons, and is needed for reuptake of glutamate by these neurons."

"The human ascorbate transporter requires zinc for the movement of vitamin C into target tissues.8 Zinc cooperates with vitamin C in regulating the oxidative environment within the cell."

[Why brain effects haven't been documented before?]
"Perhaps the severe restrictions of vitamin C experienced by sailors centuries ago produced clinically significant symptoms, such as hemorrhage, weakness, and even death, before brain stores of vitamin C were depleted. The brain is typically the last organ depleted of vitamin C.14"

"Another important question, specific not just to Mr. P, but for any patient with evidence of malnutrition, is whether other micro- or macronutrients may be involved. Micronutrient deficiencies may be more likely to occur in clusters, rather than as isolated findings.2,15 Among micronutrients, deficiency of either vitamin C or E, or of selenium, may increase the risk of Parkinsonism.16 Patients receiving chronic parenteral nutrition may be at risk for manganese intoxication, which is another cause of Parkinsonism. 17,18 In Mr. P’s case, manganese intoxication was not suspected because he was not receiving par- enteral nutrition during the time he had Parkinsonism. Vitamin E deficiency can cause motor abnormalities and dementia. However, acquired deficiency of vitamin E is very rare, and Mr. P lacked the cerebellar findings typical of vitamin E deficiency.19 Selenium deficiency may be as prevalent as vitamin C deficiency.15"

"The available laboratory studies and clinical findings led the authors to conclude that a deficiency of vitamin C, aggravated by a deficiency of zinc, best explained Mr. P’s Parkinsonism and refeeding syndrome."

"Just as Wernicke’s encephalopathy may be precipitated by refeeding, even when some thiamine is given, so perhaps may peripheral symptoms of scurvy be precipitated even when some vitamin C is provided.27"

(the previous article has a more detailed discussion on factors affecting requirement)​

So it's possible that when the body is rebuilding itself or is challenged by the conditions above, vitamin C requirements might remain elevated until correction.

 

[Amazoniac]

First bioarchaeological evidence of probable scurvy in Southeast Asia: Multifactorial etiologies of vitamin C deficiency in a tropical environment

"The primary pathological manifestation of scurvy is hemorrhage from ruptured blood vessels, which have a weakened structure from impaired collagen formation (Brickley and Ives, 2008). Ortneret al. (1999, 2001) and Ortner and Ericksen (1997) have described the pathological features of scurvy in skeletal remains as including new bone formation and abnormal porosity on specific areas of the skull."

"Skull fractures and hemorrhage are not uncommon in child abuse cases (Buckley and Whittle, 2008)."

"A restrictive diet caused by an inhospitable climate has often been cited as a cause of scurvy (Brown and Ortner, 2011; Saliset al., 2005; Schultz et al., 2007). Studies of people living in either cold climates (Brown and Ortner, 2011) or mountain environments (Salis et al., 2005; Schultz et al., 2007) indicated that such settings restricted the procurement of fresh fruit and vegetables only at specific times of the year, if at all (but for a contrasting regional perspective, see Mays, in this issue). As such, the prevalence of scurvy was relatively high; 27.9% (n = 12/43) fromthe Puy St. Pierre church in the western Alps of France (Salis et al.,2005) and 32.3% (n = 84/260) from the Grasshopper Pueblo site inthe North America Southwest (Schultz et al., 2007). Such an argument cannot apply to our case from the Cardamom Mountains, where the tropical environment allowed year-round procurement of green leafy vegetables and fruits high in vitamin C. Martin’s (1971) ethnographic survey of the plants used by Cardamom Mountain dwellers in the 1960s included vitamin C-rich species such as Carica papaya (papaya), Annona reticulata (custard apple), Zingiber officinale (ginger), Psidium guajava (guava), Citrus aurantifolia (lime), Citrus sinensis (orange), Dioscorea bulbifera (air potato), Litchi sinensis (lychee), Brassica oleracea (kale) and Mangifera indica (mango)."

"A number of variables can increase an individual’s metabolic requirement for vitamin C, but these have generally been overlooked in bioarchaeological studies. Several medical conditions involve higher than normal metabolism of vitamin C, including major trauma, burns, severe critical illness, pancreatitis, anemia, rheumatoid arthritis, diabetes, and infections (Berger, 2009; Bonham et al., 1999; Holley et al., 2011; Jacob, 1999; Long et al.,2003; Luo et al., 2008; Na et al., 2006; Naidu, 2003; Sauberlich,1994; Schorah et al., 1996). In some cases, intensive care patients can develop scurvy even with vitamin supplementation (Perretet al., 2007). Most such conditions cannot be assessed due to the limited effect they would have had on skeletal tissue and the poor preservation of the child from Jar 6. Infections have been shown to increase metabolic demand for vitamin C. For example, a significant link between Helicobacter pylori infection and lowered levels of vitamin C has been found (Lahner et al., 2012). H. pylori is a Gram-negative bacteria that has infected more than half of the world’s population (Lahner et al., 2012). Perhaps more pertinent to our case study is the link in children between moderate to high levels of Plasmodium falciparum infection and decreased ascorbic acid levels when compared to control groups (Egwunyenga et al., 2004; Isamah and Asagba, 2003; Raza et al., 2010). This is of particular relevance as P. falciparum malaria is endemic in the Cardamom Mountains and many other areas of Southeast Asia (Incardona et al., 2007). The presence of lesions suggestive of anemia signals the potential synergism of at least two conditions within this child."

"The common underlying mechanism for anemia is usually a failure to produce sufficient quantities of red blood cells (van Hensbroeket al., 2011). There are many etiologies of anemia including malaria, bacteremia, hookworm, vitamin A deficiency, vitamin B deficiency, iron deficiency, and folate deficiency. The status of iron, folic acid, and ascorbic acid in the body are linked, meaning that anemia is common in people with scurvy and vice versa (Clark et al., 1992; Cohen and Paeglow, 2001; Fairgrieveand Molto, 2000; Oeffinger, 1993). For instance, iron deficiency can cause folic acid deficiency (Herbig and Stover, 2002; Velez et al.,1966), and may lead to vitamin C deficiencies (Fairgrieve and Molto, 2000). Excess iron results in iron-driven oxidative stress. As vitamin C is an antioxidant used during such stress responses, it can lead to iron-mediated scurvy (Sadrzadeh and Eaton, 1988; Wapnick et al.,1968). Iron overload can be caused by idiopathic hemochromatosis or anemia (Wapnick et al., 1968). Thus, it is possible that anemia caused an ascorbic acid deficiency in the child from Phnom Khnang Peung. As noted, there is a strong relationship between anemia and malaria, and in those regions where P. falciparum malaria isendemic, it is a common cause of anemia (Biemba et al., 2000; Ekvall et al., 2001; Newton et al., 1997; van Hensbroek et al., 2011). Malarial infection is thought to cause anemia through both an increase in hemolysis and inadequate production of red blood cells (Abdalla and Pasvol, 2004; Pradhan, 2009). Such an outcome may occur in cases irrespective of parasitemia (Wickramasinghe et al.,1982). Therefore, it is not inconceivable that scurvy and anemia could have been caused by P. falciparum infection, with vitamin C deficiency stemming from either the infection itself or resultant anemia. There is also evidence that other parasite infections, particularly hookworm, can lead to anemia and so could potentially have played a role in our case study (Calis et al., 2007, 2008; Stoltzfuset al., 1997; van Hensbroek et al., 2011)."

"Absorption of vitamin C occurs in the small intestine, and a number of gastrointestinal diseases may cause its malabsorption. Malabsorption can result in the depletion of ascorbic acid levels within one’s body despite adequate vitamin C dietary intake, although such conditions are rare. Malabsorption syndromes occur in Whipples disease, Celiacs’s disease, Crohn’s disease, and cancer patients suffering from nausea and diarrhea (Fain, 2005; Linaker,1979; Popovich et al., 2009). Perhaps even more rare, is the possibility of newborns being vitamin C deficient at the time of birth. If the mother has insufficient ascorbic acid levels, the fetus will not be able to absorb vitamin C through the placental interface and in some cases neonates can be born vitamin C deficient (Popovichet al., 2009; Tienboon et al., 1983)."

"Various infections may lead to malabsorption of ascorbic acid. Buckley (2000) considers this an explanation for the presence of scurvy in the skeletal remains of pre-European inhabitants of Tonga. She proposes a synergistic relationship between infection (weanling diarrhea and yaws) and metabolic disease (scurvy) causing pathological lesions within this tropical environment, which was characterized by a wide range of endemic infectious diseases (Buckley, 2000, 503)."

"Genetic factors can also play a role in regulating levels of ascorbic acid, and could conceivably contribute to lowering ascorbic acid levels in the case described here. A genetic attribute known to affect vitamin C levels is the haptoglobin polymorphism. There are twodifferent haptoglobin alleles: Hp1 and Hp2. These result in three phenotypic expressions: Hp 1-1, Hp 1-2, and Hp 2-2 (Dobryszycka,1997; Na et al., 2006). Hp 2-2 polymorphism is associated with abnormal vitamin C metabolism (lowered plasma ascorbate). People with this polymorphism are also less efficient in removing free hemoglobin from the plasma, which can lead to iron-mediated vitamin C depletion (Langlois et al., 1997). An Hp 2-2 polymorphism can contribute to vitamin C deficiency through two different pathways; the polymorphism itself may cause lowered ascorbic acid levels, or the polymorphism may contribute to the development of anemia, which in turn led to scurvy either through folic acid depletion or iron overload."

First link from previous post for more information on this.​

"The Hp 2-2 phenotype has been associated with significantly lowered ascorbic acid levels (Delanghe et al., 2007, 2011; Langloisand Delanghe, 1996; Langlois et al., 1997; Na et al., 2006), increased serum iron levels in males (Langlois et al., 2000; van Vlierbergheet al., 2001), and an increased risk of developing anemia in malaria endemic regions (Atkinson et al., 2006)."​

 

[Blossom]

"The primary pathological manifestation of scurvy is hemorrhage from ruptured blood vessels, which have a weakened structure from impaired collagen formation (Brickley and Ives, 2008). Ortneret al. (1999, 2001) and Ortner and Ericksen (1997) have described the pathological features of scurvy in skeletal remains as including new bone formation and abnormal porosity on specific areas of the skull."

"Skull fractures and hemorrhage are not uncommon in child abuse cases (Buckley and Whittle, 2008)."

"A restrictive diet caused by an inhospitable climate has often been cited as a cause of scurvy (Brown and Ortner, 2011; Saliset al., 2005; Schultz et al., 2007). Studies of people living in either cold climates (Brown and Ortner, 2011) or mountain environments (Salis et al., 2005; Schultz et al., 2007) indicated that such settings restricted the procurement of fresh fruit and vegetables only at specific times of the year, if at all (but for a contrasting regional perspective, see Mays, in this issue). As such, the prevalence of scurvy was relatively high; 27.9% (n = 12/43) fromthe Puy St. Pierre church in the western Alps of France (Salis et al.,2005) and 32.3% (n = 84/260) from the Grasshopper Pueblo site inthe North America Southwest (Schultz et al., 2007). Such an argument cannot apply to our case from the Cardamom Mountains, where the tropical environment allowed year-round procurement of green leafy vegetables and fruits high in vitamin C. Martin’s (1971) ethnographic survey of the plants used by Cardamom Mountain dwellers in the 1960s included vitamin C-rich species such as Carica papaya (papaya), Annona reticulata (custard apple), Zingiber officinale (ginger), Psidium guajava (guava), Citrus aurantifolia (lime), Citrus sinensis (orange), Dioscorea bulbifera (air potato), Litchi sinensis (lychee), Brassica oleracea (kale) and Mangifera indica (mango)."

"A number of variables can increase an individual’s metabolic requirement for vitamin C, but these have generally been overlooked in bioarchaeological studies. Several medical conditions involve higher than normal metabolism of vitamin C, including major trauma, burns, severe critical illness, pancreatitis, anemia, rheumatoid arthritis, diabetes, and infections (Berger, 2009; Bonham et al., 1999; Holley et al., 2011; Jacob, 1999; Long et al.,2003; Luo et al., 2008; Na et al., 2006; Naidu, 2003; Sauberlich,1994; Schorah et al., 1996). In some cases, intensive care patients can develop scurvy even with vitamin supplementation (Perretet al., 2007). Most such conditions cannot be assessed due to the limited effect they would have had on skeletal tissue and the poor preservation of the child from Jar 6. Infections have been shown to increase metabolic demand for vitamin C. For example, a significant link between Helicobacter pylori infection and lowered levels of vitamin C has been found (Lahner et al., 2012). H. pylori is a Gram-negative bacteria that has infected more than half of the world’s population (Lahner et al., 2012). Perhaps more pertinent to our case study is the link in children between moderate to high levels of Plasmodium falciparum infection and decreased ascorbic acid levels when compared to control groups (Egwunyenga et al., 2004; Isamah and Asagba, 2003; Raza et al., 2010). This is of particular relevance as P. falciparum malaria is endemic in the Cardamom Mountains and many other areas of Southeast Asia (Incardona et al., 2007). The presence of lesions suggestive of anemia signals the potential synergism of at least two conditions within this child."

"The common underlying mechanism for anemia is usually a failure to produce sufficient quantities of red blood cells (van Hensbroeket al., 2011). There are many etiologies of anemia including malaria, bacteremia, hookworm, vitamin A deficiency, vitamin B deficiency, iron deficiency, and folate deficiency. The status of iron, folic acid, and ascorbic acid in the body are linked, meaning that anemia is common in people with scurvy and vice versa (Clark et al., 1992; Cohen and Paeglow, 2001; Fairgrieveand Molto, 2000; Oeffinger, 1993). For instance, iron deficiency can cause folic acid deficiency (Herbig and Stover, 2002; Velez et al.,1966), and may lead to vitamin C deficiencies (Fairgrieve and Molto, 2000). Excess iron results in iron-driven oxidative stress. As vitamin C is an antioxidant used during such stress responses, it can lead to iron-mediated scurvy (Sadrzadeh and Eaton, 1988; Wapnick et al.,1968). Iron overload can be caused by idiopathic hemochromatosis or anemia (Wapnick et al., 1968). Thus, it is possible that anemia caused an ascorbic acid deficiency in the child from Phnom Khnang Peung. As noted, there is a strong relationship between anemia and malaria, and in those regions where P. falciparum malaria isendemic, it is a common cause of anemia (Biemba et al., 2000; Ekvall et al., 2001; Newton et al., 1997; van Hensbroek et al., 2011). Malarial infection is thought to cause anemia through both an increase in hemolysis and inadequate production of red blood cells (Abdalla and Pasvol, 2004; Pradhan, 2009). Such an outcome may occur in cases irrespective of parasitemia (Wickramasinghe et al.,1982). Therefore, it is not inconceivable that scurvy and anemia could have been caused by P. falciparum infection, with vitamin C deficiency stemming from either the infection itself or resultant anemia. There is also evidence that other parasite infections, particularly hookworm, can lead to anemia and so could potentially have played a role in our case study (Calis et al., 2007, 2008; Stoltzfuset al., 1997; van Hensbroek et al., 2011)."

"Absorption of vitamin C occurs in the small intestine, and a number of gastrointestinal diseases may cause its malabsorption. Malabsorption can result in the depletion of ascorbic acid levels within one’s body despite adequate vitamin C dietary intake, although such conditions are rare. Malabsorption syndromes occur in Whipples disease, Celiacs’s disease, Crohn’s disease, and cancer patients suffering from nausea and diarrhea (Fain, 2005; Linaker,1979; Popovich et al., 2009). Perhaps even more rare, is the possibility of newborns being vitamin C deficient at the time of birth. If the mother has insufficient ascorbic acid levels, the fetus will not be able to absorb vitamin C through the placental interface and in some cases neonates can be born vitamin C deficient (Popovichet al., 2009; Tienboon et al., 1983)."

"Various infections may lead to malabsorption of ascorbic acid. Buckley (2000) considers this an explanation for the presence of scurvy in the skeletal remains of pre-European inhabitants of Tonga. She proposes a synergistic relationship between infection (weanling diarrhea and yaws) and metabolic disease (scurvy) causing pathological lesions within this tropical environment, which was characterized by a wide range of endemic infectious diseases (Buckley, 2000, 503)."

"Genetic factors can also play a role in regulating levels of ascorbic acid, and could conceivably contribute to lowering ascorbic acid levels in the case described here. A genetic attribute known to affect vitamin C levels is the haptoglobin polymorphism. There are twodifferent haptoglobin alleles: Hp1 and Hp2. These result in three phenotypic expressions: Hp 1-1, Hp 1-2, and Hp 2-2 (Dobryszycka,1997; Na et al., 2006). Hp 2-2 polymorphism is associated with abnormal vitamin C metabolism (lowered plasma ascorbate). People with this polymorphism are also less efficient in removing free hemoglobin from the plasma, which can lead to iron-mediated vitamin C depletion (Langlois et al., 1997). An Hp 2-2 polymorphism can contribute to vitamin C deficiency through two different pathways; the polymorphism itself may cause lowered ascorbic acid levels, or the polymorphism may contribute to the development of anemia, which in turn led to scurvy either through folic acid depletion or iron overload."

First link from previous post for more information on this.​

"The Hp 2-2 phenotype has been associated with significantly lowered ascorbic acid levels (Delanghe et al., 2007, 2011; Langloisand Delanghe, 1996; Langlois et al., 1997; Na et al., 2006), increased serum iron levels in males (Langlois et al., 2000; van Vlierbergheet al., 2001), and an increased risk of developing anemia in malaria endemic regions (Atkinson et al., 2006)."​

Amazing find. Thanks for your in-depth contributions on this and many other topics @Amazoniac.

 

[LeeLemonoil]

I second the sentiment from @Blossom .
Thanks a lot @Amazoniac


I can provide this anecdotal, subjective thingy:

Vitamin C of ~500-759mg dissolved in two sips of water has the same stress and anxiety lowering effect that aspirin at 300mg never fails to give me.
It’s seldom that I feel that way, but if I do - mostly before noon - both agents would help me within an hour. The effects feel similar. I‘d guess both drastically reduce cortisol spikes

 

[Amazoniac]

Michel Langlois (one of the authors of the 'more than a nutritional disorder' article)

↳ Plasma vitamin C for predicting cardiovascular disease: More than a nutritional biomarker

"Vitamin C status in humans is not only determined by dietary vitamin C content, but also by environmental and lifestyle factors (e.g., smoking), biological factors (e.g., inflammation, iron excess), and pathological conditions (e.g., malabsorption, chronic haemolysis) (Table 1). Here we further wish to point towards potential confounding by inflammation, iron status, and iron-related genetic polymorphisms as important determinants of plasma vitamin C (7)."

A few more included this time.​

"Low plasma vitamin C concentrations have been observed in peripheral arterial disease patients with pronounced inflammation, despite a largely sufficient nutritional supply of vitamin C (8). This effect is attributable to the inflammatory response within atherosclerotic lesions and the subsequent release of reactive oxygen species (ROS) by activated macrophages, which results in oxidative stress (8). Plasma vitamin C negatively correlates with high-sensitive C-reactive protein (hs-CRP) concentration, a marker of subclinical inflammation associated with increased cardiovascular risk. Serum concentration of hs-CRP and other inflammation-sensitive plasma proteins (ISPs, e.g., serum amyloid A, fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, orosomucoid) can predict cardiac events and ischemic stroke (9,10). Therefore, hs-CRP or other ISPs should be assessed in studies linking vitamin C with CVD."

"Iron and vitamin C status are closely related. Paradoxically, vitamin C exhibits harmful pro-oxidant effects in presence of iron (11,12). This pro-oxidant effect is due to the ability of ascorbic acid to reduce ferric iron (Fe3+) back to ferrous iron (Fe2+) that can generate ROS (Fenton chemistry) and induce lipid oxidation (11). Vitamin C can release toxic Fe2+ from intracellularly sequestered iron stores (ferritin), a reaction in which ascorbic acid is oxidized and depleted. Significant vitamin C depletion is evident in conditions with chronic iron overload, e.g., hemodialysis [expand the box below for more details], hemochromatosis, thalassemia, and in some diabetics (11-13). Among several common mutations and polymorphisms of genes involved in iron turnover, the haptoglobin (Hp) polymorphism has been most clearly demonstrated to affect in vivo vitamin C variability even in non-pathological conditions (14,15)."

"From these observations, it is clear that many biological and lifestyle factors might seriously confound the relation between plasma vitamin C and CVD. Additional limitations of vitamin C as a laboratory marker are its instability in vitro when not protected from air (oxygen) and light, and its rapid degradation without rigorous pre-analytical sample handling. Blood samples should be analysed immediately (within 30 min), or not later than 3 h if the specimen is refrigerated. Even minimal in vitro haemolysis accelerates the decomposition of ascorbic acid due to release of redoxactive free Hb (14). It is recommended to deproteinize the plasma or serum promptly with metaphosphoric acid or trichloro-acetic acid."

"In conclusion, the classical view of plasma vitamin C being a biomarker mainly reflecting nutritional intake needs to be refined. Further adjustment for several non-nutritional and genetic factors would provide additional insights in studies of the association between vitamin C status and CVD risk."​

↳ Vitamin C Deficiency and Scurvy Are Not Only a Dietary Problem but Are Codetermined by the Haptoglobin Polymorphism

Spoiler: Fig. 1 - The effects of haptoglobin polymorphism on vitamin C metabolism

Spoiler: Potential issues in kidney disease and iron overload disorders

↳ Oral Vitamin C Administration Increases Lipid Peroxidation in Hemodialysis Patients

"Vitamin C maintains metal ions in the active center in a reduced state and thus promotes an optimal enzymatic activity."

"Vitamin C deficiency is common in chronic hemodialysis patients. First, dialysis patients have a reduced overall food intake, with a particular restriction of nutritionally valuable items as fresh fruits and vegetables. Second, AA is water-soluble, has a low molecular weight and a low albumin binding. Vitamin losses into the dialysate may mount up to several hundred milligrams per week in unsupplemented patients [3, 4]. Finally, the reduced form of vitamin C is decreased in hemodialysis patients [5], perhaps as a result of increased vitamin oxidation catalyzed by iron, abnormal oxidant production and defective antioxidant mechanisms. Low vitamin C plasma levels predicted adverse cardiovascular outcome in chronic hemodialysis patients [6]. Therefore, systematic vitamin C supplementation has been recommended in maintenance hemodialysis patients, although no consensus exists on the appropriate dose."

"More recently, vitamin C has garnered attention as a potential adjuvant to erythropoietin." "[..]vitamin C facilitates mobilization of iron from inert tissue stores and improves iron incorporation into protoporphyrin for heme synthesis [7, 8]. Administration of 300 mg [9–11] or 500 mg [12–14] vitamin C i.v. thrice weekly resulted in a better response to erythropoietin, in patients with functional iron deficiency or erythropoietin hyporesponsiveness only [9–13] or in the general hemodialysis population irrespective of baseline iron status [14]. In a cross-sectional study of 130 hemodialysis patients, serum AA had a small (5%) but significant impact on the response to exogenous erythropoietin, independent of indicators of iron status, inflammation and oxidative stress [15]. The European Best Practice Guidelines on Anemia management therefore advise to correct vitamin C status especially in hemodialysis patients with functional iron deficiency [16]."

"However, chronic vitamin C supplementation in excess of 500 mg/wk results in increased oxalate generation with a potential risk of oxalosis [4]. Even more importantly, vitamin C may have a paradoxical pro-oxidant effect in the presence of iron and thus cause oxidative damage to biological macromolecules. In vitro, the reduction of transition metal ions by ascorbate leads to the production of reactive oxygen species [1]. The relevance of this Fenton chemistry in vivo has been the matter of some controversy. Several vitamin C and iron co-supplementation studies in animals and healthy volunteers indicate that vitamin C inhibits rather than promotes iron-dependent oxidative damage [1]. A number of issues preclude, however, extrapolation of these results to the chronic hemodialysis population. In healthy volunteers with adequate baseline vitamin C status, subsequent supplementation cannot have an effect on tissue AA levels and thus oxidative biomarkers [17]. Conversely, pro-oxidant effects cannot be excluded in vitamin C-deficient hemodialysis patients. In addition, the timing of intervention appears to be important. Vitamin C acted as an anti-oxidant if added before initiation of LDL oxidation, but acted as a pro-oxidant if added to LDL that was already mildly oxidized [18]. These findings may be of major relevance in the hemodialysis population with increased oxidative stress."

"Vitamin C supplements are often given to chronic hemodialysis patients either to compensate for deficient oral intake and vitamin C losses in the dialysate, or to mobilize inert storage iron and thus improve the response to erythropoietin. At face value, vitamin C is an attractive adjuvant in patients with erythropoietin hyporesponsiveness, but little attention has been paid to safety issues. A vitally important and unanswered question is whether vitamin C may act as a pro-oxidant in hemodialysis patients, in particular in the presence of iron overload. If vitamin C causes oxidative tissue injury in these circumstances, the adverse consequences of accelerated atherosclerosis or vulnerability to infection may largely outweigh the potential benefit of improved erythropoiesis."

"In the present study of 109 hemodialysis patients, [] the oral administration of vitamin C (360 and 1,500 mg/week) resulted in a dose-dependent rise of plasma MDA [more information in the second-last link, but you must all be familiar with it], a lipid oxidation-derived compound. Importantly, MDA correlated at baseline with plasma lipids, but not with serum ferritin. After treatment with vitamin C, however, MDA correlated strongly and independently with serum AA and serum ferritin. The latter observation indicates that dialysis patients with high serum ferritin levels may be especially vulnerable to the pro-oxidant effects of vitamin C in vivo. Indeed, AA acts by releasing Fe2+ from ferritin in inert iron storage sites, thereby promoting Fenton chemistry. Functional iron deficiency is biochemically characterized by low transferrin saturation and high serum ferritin levels and is a common cause of erythropoietin hyporesponsiveness in hemodialysis patients. The use of vitamin C has been touted in particular in patients with functional iron deficiency [9–13]. The results of the present study suggest, however, that precisely those patients may suffer most from the undesirable effects of vitamin C. The correlations of serum AA and ferritin with MDA were independent in a multivariate analysis, suggesting that additional pro-oxidant effects of vitamin C, unrelated to iron stores, may play a role. Although it was not an endpoint, it should be noted that vitamin C did not alter erythropoietin requirements in our patients. In addition, vitamin C had no effect on any other measured parameter relating to iron status, nutrition and inflammation, dialysis efficiency or plasma lipids."

"In line with previous observations, vitamin C deficiency was very common (44.4%) in patients on hemodialysis and baseline serum AA correlated with vitamin C intake and with smoking status. A dose of 360 mg/week was insufficient to restore vitamin C status in this population, since 26.5% of patients maintained serum AA levels under the lower reference limit of 0.2 mg/dl. Only after administration of 1,500 mg/week did the majority of patients have serum AA concentrations within reference limits. After vitamin C supplementation, plasma MDA correlated with serum AA and the change of serum AA from baseline. These results indicate that lipid peroxidation occurs especially in those patients with the highest rise of vitamin C levels and suggest that the correction of vitamin C status in vitamin C-deficient hemodialysis patients may be undesirable."

"A limitation of this study is the lack of a placebo group." (there are others below)

"Serum AA and plasma MDA returned to baseline after withdrawal of vitamin C."

"In conclusion, oral low- and moderate-dose vitamin C supplementation increases lipid peroxidation in hemodialysis patients. We contend that the potential laudable effect of restoring vitamin C status or improving erythropoiesis in a chronic hemodialysis population may be entirely overruled by the consequences of oxidative tissue injury. Our findings set the stage for the design of a large randomized controlled trial on the efficacy and safety of vitamin C administration in chronic hemodialysis patients, with particular attention to the long-term consequences of increased oxidative stress."​

- Lipid peroxidation in hemodialysis patients: Effect of vitamin C supplementation
- Vitamin C supplementation in kidney failure: effect on uraemic symptoms

- Vitamins in dialysis: who, when and how much? (on positive and negative effects)

- Oxidative Stress in Kidney Diseases: The Cause or the Consequence?

- The Role of Ascorbic Acid in the Metabolism of Storage Iron

--
Blossom and Lee, it's nice to read that these are being useful.

 

[InChristAlone]

Efficacy of Ascorbic Acid in Reducing Glyphosate-Induced Toxicity in Rats
"...administering the affected animals with ascorbic acids might reduce the toxicity inflicted by the glyphosate."

 

[Mito]

Metabolic syndrome patients need more vitamin C to break cycle of antioxidant depletion

A higher intake of vitamin C is crucial for metabolic syndrome patients trying to halt a potentially deadly cycle of antioxidant disruption and health-related problems, an Oregon State University researcher says.

That's important news for the estimated 35 percent of the U.S. adult population that suffers from the syndrome.

"What these findings are really saying to people as we move out of the rich-food holiday season and into January is eat your fruits and vegetables," said Maret Traber, a professor in the OSU College of Public Health and Human Sciences and Ava Helen Pauling Professor at Oregon State's Linus Pauling Institute. "Eat five to 10 servings a day and then you'll get the fiber, you'll get the vitamin C, and you'll really protect your gut with all of those good things."

A diet high in saturated fat results in chronic low-grade inflammation in the body that in turn leads to the development of metabolic syndrome, a serious condition associated with cognitive dysfunction and dementia as well as being a major risk factor for cardiovascular disease, fatty liver disease and type 2 diabetes.

A patient is considered to have metabolic syndrome if he or she has at least three of the following conditions: abdominal obesity, high blood pressure, high blood sugar, low levels of "good" cholesterol, and high levels of triglycerides.

Findings published in Redox Biology suggest the type of eating that leads to metabolic syndrome can prompt imbalances in the gut microbiome, with impaired gut function contributing to toxins in the bloodstream, resulting in vitamin C depletion, which subsequently impairs the trafficking of vitamin E.

It's a treadmill of antioxidant disruption that serves to make a bad situation worse; antioxidants such as vitamins C and E offer defense against the oxidative stress brought on by inflammation and the associated free radicals, unstable molecules that can damage the body's cells.

"Vitamin C actually protects vitamin E, so when you have lipid peroxidation, vitamin E is used up and vitamin C can regenerate it," Traber said. "If you don't have the vitamin C, the vitamin E gets lost and then you lose both of those antioxidants and end up in this vicious cycle of depleting your antioxidant protection."

Lipid peroxidation is the oxidative degradation of polyunsaturated fatty acids that are a major component of living cells; it's the process by which free radicals try to stabilize themselves by stealing electrons from cell membranes, causing damage to the cell.

"If there's too much fat in the diet, it causes injury to the gut," Traber said. "Bacterial cell walls can then leak from the gut and slip into circulation in the body, and they're chased down by neutrophils."

Neutrophils are the most abundant type of white blood cells, a key part of the immune system. Neutrophils attack bacteria with hypochlorous acid: bleach.

"The white blood cells are scrubbing with bleach and that destroys vitamin C," Traber said. "The body is destroying its own protection because it got tricked by the gut dysbiosis into thinking there was a bacterial invasion."

And without intervention, the process keeps repeating.

"People with metabolic syndrome can eat the same amount of vitamin C as people without metabolic syndrome but have lower plasma concentrations of vitamin C," Traber said. "We're suggesting that's because this slippage of bacterial cell walls causes the whole body to mount that anti-inflammatory response."

Vitamin C is found in fresh vegetables and fruits; sources of vitamin E include almonds, wheat germ and various seeds and oils.

Federal dietary guidelines call for 65 to 90 milligrams daily of vitamin C, and 15 milligrams of vitamin E.

Metabolic syndrome patients need more vitamin C to break cycle of antioxidant depletion

 

[Amazoniac]

- Urinary acidification with ascorbic acid (by Travis and friends)

"Acidification of urine as an adjunct in the therapy of chronic urinary tract infection has been employed for a number of years. For this purpose McDonald and Murphy[1] in 1959 proposed the use of ascorbic acid. Their study revealed that ascorbic acid, when administered every 4 hours in a daily dose of 2.5 Gm. (equivalent to approximately 1.5 Gm. per square meter per day) was "capable of significantly lowering urinary pH" in adult subjects."

..

"Orally administered ascorbic acid, even at dose levels of 8.0 Gm. per square meter per day to [our] normal subjects, was not consistently effective in lowering the urine pH to, or below, 5.5 when given 4 times a day. The fluctuations toward "less acid" urine appear to be significantly less when ascorbic acid is administered every 4 hours day and night."

"On the basis of this study, it is suggested that, if ascorbic acid is used for sustained urinary acidification (pH below 5.5), two conditions must be met: It must be given (1) in large amounts and (2) at intervals of 4 hours day and night. Isolated urine pH determinations cannot be relied upon as a basis to judge the constancy and degree of urinary acidification."​

- The Roles of Vitamin C in Skin Wealth

--
Does the amount of collagen ingested change the requirement for vit C?

 

[yerrag]

"Acidification of urine as an adjunct in the therapy of chronic urinary tract infection has been employed for a number of years. For this purpose McDonald and Murphy[1] in 1959 proposed the use of ascorbic acid. Their study revealed that ascorbic acid, when administered every 4 hours in a daily dose of 2.5 Gm. (equivalent to approximately 1.5 Gm. per square meter per day) was "capable of significantly lowering urinary pH" in adult subjects."

..

"Orally administered ascorbic acid, even at dose levels of 8.0 Gm. per square meter per day to [our] normal subjects, was not consistently effective in lowering the urine pH to, or below, 5.5 when given 4 times a day. The fluctuations toward "less" urine appear to be significantly less when ascorbic acid is administered every 4 hours day and night."

"On the basis of this study, it is suggested that, if ascorbic acid is used for sustained urinary acidification (pH below 5.5), two conditions must be met: It must be given (1) in large amounts and (2) at intervals of 4 hours day and night. Isolated urine pH determinations cannot be relied upon as a basis to judge the constancy and degree of urinary acidification."

So, is the urine acidity at 5.5 or less going to solve the urinary tract infection? If so, how long should the urine acidity have to stay at 5.5 or less? I suppose that for a limited duration, the body can tolerate such low urine pH. But then the body will have to go back to having its acid-base balance restored, otherwise being in an acidic state for a long period will cause excessive urination, loss of electrolytes and b1, to name a few nutrients lost, and it will weaken the immune system.