Vitamin C Is An Endotoxin Antagonist And Can Reduce Cortisol And Inflammation

[InChristAlone]

What about Vitamin Cs effect on Hormones ?
I took 3 gram of Vitamin C on an empty stomach and I started getting the famous scalp itch that is followed by hair loss. Also felt less masculine. So there could be some estrogenic effects . Not sure...
I would like to take Vitamin C esp. for LPS antagonism, which would also benefit my liver. So maybe I will keep the dosage in the 1-2 g range and see if I still experience some benefits... According to OPs study less than a half a gram should give protection from LPS if taken with a meal
What dosages are you guys taking ?
If It is estrogen it should be more than enough to stack it with a drop and Androsterone.


"AsA causes decrease in the nonpregnant isolated uterine smooth muscle tissue levels of progesterone and increase in the non-pregnant isolated uterine smooth muscle tissue levels of estrogen"
http://www.jcgo.org/index.php/jcgo/article/viewFile/47/39

The HED translates to about 400mg , which is isnt really much. It was intraperitoneally ,which leads to great absorption. So no Idea how much oral Vitamin C would be needed to achieve the same blood concentration , but for sure several grams!

What a barbaric study. That proves nothing. No one is shoving vitamin C up their vagina! And there are studies showing it can increase progesterone so this wasn't conclusive on how it effects hormone levels at all. Not to mention there are many many 'vitamin C babies' in a large orthomolecular group I am in. Some have said what an easy pregnancy and delivery it was as compared to other babies they had.

I just took 8 grams this morning. No scalp itch.

 

[Mauritio]

No need to be defensive about Vitamin C . I wasnt trying to discredit it.
And actually intrapertioneal injection is really common in animals. Intraperitoneal injection - Wikipedia
Also the scalp itch seems to be a male phenomenon, never heard of a woman having it.

 

[InChristAlone]

No need to be defensive about Vitamin C . I wasnt trying to discredit it.
And actually intrapertioneal is really common in animals. Intraperitoneal injection - Wikipedia
Also the scalp itch seems to be a male phenomenon, never heard of a woman having it.

I have gotten the itch after eating certain things.

 

[Mauritio]

I have gotten the itch after eating certain things.

Interesting. Did you also get hair loss /shedding after that?

 

[Amazoniac]

Will is vitamin E when C is depleted from inflammation?

The Relationship Between Vitamin C Status, the Gut-Liver Axis, and Metabolic Syndrome

Their key points:

- "Excess dietary energy provokes gut dysbiosis leading to increased inflammation."
- "Impairments in gut function contribute to metabolic endotoxemia."
- "Endotoxemia depletes vitamin C, which in turn impairs vitamin E trafficking."
- "Higher vitamin C intake can restore gut-liver functions and antioxidant status."​

"Inadequate vitamin C intakes clearly impair vitamin C status [4]; however, ascorbic acid is also depleted systemically by its reaction with hypochlorous acid (bleach), an anti-microbial agent produced by neutrophils [12]. Although no studies have explicitly tested the hypothesis, the objective of this review is to present evidence supporting that poor vitamin C status in MetS is driven by gut inflammation and barrier dysfunction attributed to excess dietary energy consumption [13]. Importantly, impaired gut barrier function in MetS mediates metabolic endotoxemia by increasing the absorption of bacteria and gut-derived endotoxins (e.g. lipopolysaccharide (LPS)) [13,14] while also impairing vitamin C absorption [15]. These inter-related events provoke a vicious cycle, both increasing chronic inflammation and oxidative damage."

"[..]because LPS triggers intestinal and hepatic inflammation, we propose that improved vitamin C status along the gut-liver axis would restore vitamin E trafficking and bioavailability that is otherwise impaired in MetS persons, likely due to their heightened inflammation in association with poor vitamin C status [18,19]."

"Potentially, inadequate vitamin C status in MetS contributes to small intestinal bacterial overgrowth, transcytosis of enteric bacteria, and an elevation of circulating LPS, which elicits a low-grade inflammatory response. By contrast, oral ingestion of large-dose vitamin C supplements results in limited intestinal vitamin C absorption [26], with excess ascorbic acid remaining in the gut lumen where it can potentially exert beneficial effects both on the intestinal cells and microbiota composition and function."

@Roselle525 - it's something we have been considering.
​

"Normally, LPS is absorbed from the intestine bound to the LPS-binding protein attached to chylomicrons [31]. This chylomicron-dependent mechanism protects against TLR4-induced inflammation by directing LPS to the lymphatics instead of the portal stream, sequestering LPS away from circulating white cells by instead delivering it to the liver for detoxification [32]. However, increased LPS absorption is promoted by a high-fat diet that not only increases chylomicron secretion, but also increases gut barrier dysfunction, thereby allowing LPS passage and increasing circulating LPS, which potentiates endotoxemia-associated inflammation [13,33-35]."

"Our assessment of a limited population of relatively healthy adults with MetS shows that, in association with lower vitamin C status, persons with MetS not only have metabolic endotoxemia (unpublished observation; Figure 2) and increased biomarkers of inflammation but also lower α-tocopherol (α-TOH) bioavailability [18,19]. These findings suggest a complex interaction between the antioxidant vitamins and endotoxin-induced inflammation, as well as with other dietary antioxidants [36]. Although causality has yet to be established, hypothetically poor vitamin C status drives metabolic endotoxemia, or conversely heightened inflammation due to endotoxemia depletes systemic vitamin C."

"Endotoxemia may also further impair the already low ascorbate status in MetS because LPS inhibits absorption of ascorbate [15] by decreasing sodium-dependent vitamin C transporters (SVCT-1 and -2) [15,38-40]. Additionally, oxidized ascorbate (i.e. dehydroascorbic acid; DHA) can be taken up by enterocytes via glucose transporters [41,42]. However, when glucose intakes are high, this mechanism has little benefit on vitamin C status because concentrations of DHA are much lower than that of glucose [43,44]. Thus, poor vitamin C status in MetS may not only be the result of low dietary vitamin C intakes [4], which are exacerbated by impaired absorption of either ascorbate or DHA."

"Animal studies support the concept that vitamin C can reduce the sequelae of MetS." "Vitamin C-deficient guinea pigs in response to endotoxemia induction have increased NF-kB responses in association with exaggerated systemic shock and impaired lung phosphatidylcholine biosynthesis [60-62], while dietary vitamin C supplementation attenuates endotoxemia and intestinal barrier defects [62]. Vitamin C-deficient ODS rats also demonstrate increased endotoxemia associated with increased liver inflammation and gut dysfunction [63], increased gastric mucosal lesions [64], acute phase responses [65], inflammatory chemokine and cytokines [66], and cytokine-induced neutrophil chemoattractant-1 (CINC-1) [66]. They also have increased LDL [67], decreased HDL [68] and impaired synthesis of apo-AI [69]. Thus, the association between vitamin C deficiency and the hallmarks of MetS (i.e. gut barrier dysfunction, increased endotoxemia, inflammation, altered lipoproteins) are supported by studies in vitamin C-deficient animals."

@Terma
​

"[..]ascorbate blocks endotoxemia [73]."

"Ascorbate reacts as an antioxidant with hypochlorous acid, an anti-microbial agent that is produced by neutrophils via myeloperoxidase (MPO) [12]. Further, intestinal and circulating neutrophils accumulate high ascorbate levels that function to protect themselves from MPO, which is activated during bacterial phagocytosis [37]. Remarkably, MPO also acts as an “ascorbate peroxidase” that directly consumes ascorbate [78]. Thus, the oxidative distress that is evident in MetS consists not only of non-specific lipid peroxidation that consumes α-TOH [79] to potentially increase the risk for NAFLD [80,81], but is also is a direct consequence of increased inflammatory responses (i.e. MPO) that deplete vitamin C. Further, we have shown that insufficient ascorbate results in the more rapid depletion of α-TOH [82,83]."

"Another potential benefit of increased vitamin C intake is the improvement in barrier function caused by increasing collagen synthesis in the intestine [77]. This proposed mechanism is consistent with ascorbate’s coenzyme function that hydroxylates proline and lysine to cross-link collagen [85]. For example, studies in the T84 human crypt-like epithelial cell line with indomethacin-induced barrier dysfunction show that bacteria cross the epithelium via a transcellular pathway, which is abrogated by treatment with vitamin C [74]. Thus, poor ascorbate status at the gut likely exacerbates barrier dysfunction that increases the translocation of LPS-derived Gram-negative bacteria to potentiate inflammation."

@Kartoffel
​

"Oxygen may play a critical role in gut health. Oxygen gradients decrease steeply from the upper to lower gastrointestinal tract and also increase from the lumen to the more vascularized epithelial layer. Oxygen regulates microbial colonization with more oxygen-tolerant bacteria in the mucosa (e.g. Helicobacter) whereas obligate anaerobes (e.g. Firmicutes) are luminal [86,87]. Oxygen gradients also contribute to microbial biogeography by influencing metabolite production and modulating redox effectors (e.g. nitric oxide, hydrogen sulfide, ROS) of either bacteria or host origin [88]. ROS generated by the intestinal epithelium [89,90] function to exert redox-responsive cell signaling (e.g. thiol redox switches) and maintain gut barrier integrity [91,92]."

"[..]in early-weaned piglets with gut dysbiosis and decreased intestinal ROS-detoxifying capacity, a vitamin C-rich antioxidant cocktail improved intestinal redox status in association with increased proportions of commensal bacteria and decreased pathogenic bacteria [95]."

"A vitamin C-rich functional food also alleviated metabolic endotoxemia and liver steatosis in a rat NAFLD model in association with improved microbiota composition (i.e. greater α-diversity, increased Firmicutes/Bacteroidetes ratio) [96]."

"Further, studies in vitro with an antioxidant cocktail containing vitamin C facilitated the successful culturing of anaerobic protozoa in association with decreasing the oxidationreduction potential (i.e. more reduced environment) and increasing acetate, a short chain fatty acid that is an important energy source for these microorganisms [97]. We therefore posit that greater vitamin C intakes can directly attenuate metabolic endotoxemia in MetS by improving gut barrier function, as well as improving microbial diversity and function."

"Increased levels of circulating LPS have been observed following strenuous aerobic exercise [98]. After exercise, the plasma ascorbate free radical (Asc-) increased, which suggests an increase in oxidative distress. However, in this study, oral vitamin C supplementation (1,000 mg) decreased LPS concentrations and increased plasma ascorbate from 29 to 121 uM. As might be expected, supplementation also increased the plasma Asc- level both before and after exercise. [98]"

"The interactions of antioxidants have been recognized by free radical chemists for decades [99,115]. We previously addressed this question by investigating the turnover kinetics of α-TOH in cigarette smokers; smokers had increased oxidative distress. We found that the disappearance of α-TOH was inversely related to plasma ascorbate levels [83], but could be normalized by vitamin C supplementation [82]. We have now focused on the possibility that α- TOH bioavailability is highly dependent upon adequacy of vitamin C, not only to recycle and maintain α-TOH [99], but also to enhance physiological functions along the gut-liver axis that facilitate trafficking of α-TOH to achieve vitamin E adequacy."

@haidut
​

"Bioavailability [116] is defined as it relates to α-TOH as the extent and rate of α-TOH incorporation into the circulation, which is dependent upon α-TOH absorption, lipoprotein incorporation, trafficking, and lipoprotein-mediated tissue uptake, as well as hepatic catabolism (Figure 3) [117]. Increased inflammation and oxidative damage in association with low vitamin C status in persons with MetS potentiated already poor α-TOH status by limiting α-TOH trafficking along the gut-liver axis [18]."

"Increased oxidative distress results in faster disappearance rates of plasma α-TOH in cigarette smokers [83,121]. Consistent with correlative evidence that low vitamin C status increases the rate of disappearance of α-TOH [83], findings from a randomized placebo-controlled cross-over study demonstrated that vitamin C supplementation (500 mg twice daily; 2-wk) restored the rates of disappearance of α-TOH to levels no different from nonsmoking persons [82]. This observation is consistent with a mechanism by which ascorbate functions as an electron-donor to reduce the α-tocopherol radical (α-TO*) back to α-TOH, the functional form as a donor antioxidant, i.e. it recycles vitamin E [99]."

"Similar to smokers, inadequate vitamin C status in MetS persons could, in part, impair α-TOH status by increasing oxidative α-TOH depletion because biomarkers of oxidative distress and inflammation are higher in MetS persons compared with healthy individuals [18,19,122] (Figure 3). Further, participants with MetS had lower plasma ascorbic acid concentrations despite eating diets with similar amounts of vitamin C as those consumed by healthy subjects for 3 days prior to completing α-TOH pharmacokinetic studies [18]. In those pharmacokinetic studies, α-TOH bioavailability was significantly reduced among MetS persons."

"The paradigm in MetS of decreased α-TOH status is best described by the concept of “physiological inadequacy” and is driven in MetS by impaired trafficking of α-TOH along the gut-liver axis [18]. The challenge to interpret the lower α-TOH bioavailability and slower plasma α-TOH turnover observed in MetS [18] is that α-TOH status is difficult to assess in hyperlipidemic individuals. Because circulating lipoproteins transport α-TOH with other lipids (e.g. triglyceride, cholesterol), elevated blood lipids “trap” α-TOH in the circulation. This process yields apparently “normal” plasma α-TOH concentrations that mask the fact that α-TOH concentrations in target tissues are inadequate, thereby permitting oxidative injury [19,123]. We propose that a urinary vitamin E catabolite, α-CEHC, can be used in conjunction with circulating α-TOH as a more reliable biomarker of α-TOH status, especially among hyperlipidemic persons where even lipidnormalized measures of α-TOH status have limited interpretation [123]."

"Inflammation likely also drives systemic depletion of ascorbate, as shown in sepsis patients [133], who despite receiving 50 or 200 mg still become deficient in vitamin C due to heightened immune responses in septic shock that increase the rate of oxidation vitamin C, resulting in its depletion [134]. Taken together, the available data support the premise that endotoxemia promotes poor vitamin C status and exacerbates inflammation along the gut-liver axis that increases the demand for antioxidant defenses, especially vitamins C and E."
​

One of the authors is a known vitamin E researcher:
- Maret G. Traber

 

[Kartoffel]

Will is vitamin E when C is depleted from inflammation?

The Relationship Between Vitamin C Status, the Gut-Liver Axis, and Metabolic Syndrome

Their key points:

- "Excess dietary energy provokes gut dysbiosis leading to increased inflammation."
- "Impairments in gut function contribute to metabolic endotoxemia."
- "Endotoxemia depletes vitamin C, which in turn impairs vitamin E trafficking."
- "Higher vitamin C intake can restore gut-liver functions and antioxidant status."​

"Inadequate vitamin C intakes clearly impair vitamin C status [4]; however, ascorbic acid is also depleted systemically by its reaction with hypochlorous acid (bleach), an anti-microbial agent produced by neutrophils [12]. Although no studies have explicitly tested the hypothesis, the objective of this review is to present evidence supporting that poor vitamin C status in MetS is driven by gut inflammation and barrier dysfunction attributed to excess dietary energy consumption [13]. Importantly, impaired gut barrier function in MetS mediates metabolic endotoxemia by increasing the absorption of bacteria and gut-derived endotoxins (e.g. lipopolysaccharide (LPS)) [13,14] while also impairing vitamin C absorption [15]. These inter-related events provoke a vicious cycle, both increasing chronic inflammation and oxidative damage."

"[..]because LPS triggers intestinal and hepatic inflammation, we propose that improved vitamin C status along the gut-liver axis would restore vitamin E trafficking and bioavailability that is otherwise impaired in MetS persons, likely due to their heightened inflammation in association with poor vitamin C status [18,19]."

"Potentially, inadequate vitamin C status in MetS contributes to small intestinal bacterial overgrowth, transcytosis of enteric bacteria, and an elevation of circulating LPS, which elicits a low-grade inflammatory response. By contrast, oral ingestion of large-dose vitamin C supplements results in limited intestinal vitamin C absorption [26], with excess ascorbic acid remaining in the gut lumen where it can potentially exert beneficial effects both on the intestinal cells and microbiota composition and function."

@Roselle525 - it's something we have been considering.
​

"Normally, LPS is absorbed from the intestine bound to the LPS-binding protein attached to chylomicrons [31]. This chylomicron-dependent mechanism protects against TLR4-induced inflammation by directing LPS to the lymphatics instead of the portal stream, sequestering LPS away from circulating white cells by instead delivering it to the liver for detoxification [32]. However, increased LPS absorption is promoted by a high-fat diet that not only increases chylomicron secretion, but also increases gut barrier dysfunction, thereby allowing LPS passage and increasing circulating LPS, which potentiates endotoxemia-associated inflammation [13,33-35]."

"Our assessment of a limited population of relatively healthy adults with MetS shows that, in association with lower vitamin C status, persons with MetS not only have metabolic endotoxemia (unpublished observation; Figure 2) and increased biomarkers of inflammation but also lower α-tocopherol (α-TOH) bioavailability [18,19]. These findings suggest a complex interaction between the antioxidant vitamins and endotoxin-induced inflammation, as well as with other dietary antioxidants [36]. Although causality has yet to be established, hypothetically poor vitamin C status drives metabolic endotoxemia, or conversely heightened inflammation due to endotoxemia depletes systemic vitamin C."

"Endotoxemia may also further impair the already low ascorbate status in MetS because LPS inhibits absorption of ascorbate [15] by decreasing sodium-dependent vitamin C transporters (SVCT-1 and -2) [15,38-40]. Additionally, oxidized ascorbate (i.e. dehydroascorbic acid; DHA) can be taken up by enterocytes via glucose transporters [41,42]. However, when glucose intakes are high, this mechanism has little benefit on vitamin C status because concentrations of DHA are much lower than that of glucose [43,44]. Thus, poor vitamin C status in MetS may not only be the result of low dietary vitamin C intakes [4], which are exacerbated by impaired absorption of either ascorbate or DHA."

"Animal studies support the concept that vitamin C can reduce the sequelae of MetS." "Vitamin C-deficient guinea pigs in response to endotoxemia induction have increased NF-kB responses in association with exaggerated systemic shock and impaired lung phosphatidylcholine biosynthesis [60-62], while dietary vitamin C supplementation attenuates endotoxemia and intestinal barrier defects [62]. Vitamin C-deficient ODS rats also demonstrate increased endotoxemia associated with increased liver inflammation and gut dysfunction [63], increased gastric mucosal lesions [64], acute phase responses [65], inflammatory chemokine and cytokines [66], and cytokine-induced neutrophil chemoattractant-1 (CINC-1) [66]. They also have increased LDL [67], decreased HDL [68] and impaired synthesis of apo-AI [69]. Thus, the association between vitamin C deficiency and the hallmarks of MetS (i.e. gut barrier dysfunction, increased endotoxemia, inflammation, altered lipoproteins) are supported by studies in vitamin C-deficient animals."

@Terma
​

"[..]ascorbate blocks endotoxemia [73]."

"Ascorbate reacts as an antioxidant with hypochlorous acid, an anti-microbial agent that is produced by neutrophils via myeloperoxidase (MPO) [12]. Further, intestinal and circulating neutrophils accumulate high ascorbate levels that function to protect themselves from MPO, which is activated during bacterial phagocytosis [37]. Remarkably, MPO also acts as an “ascorbate peroxidase” that directly consumes ascorbate [78]. Thus, the oxidative distress that is evident in MetS consists not only of non-specific lipid peroxidation that consumes α-TOH [79] to potentially increase the risk for NAFLD [80,81], but is also is a direct consequence of increased inflammatory responses (i.e. MPO) that deplete vitamin C. Further, we have shown that insufficient ascorbate results in the more rapid depletion of α-TOH [82,83]."

"Another potential benefit of increased vitamin C intake is the improvement in barrier function caused by increasing collagen synthesis in the intestine [77]. This proposed mechanism is consistent with ascorbate’s coenzyme function that hydroxylates proline and lysine to cross-link collagen [85]. For example, studies in the T84 human crypt-like epithelial cell line with indomethacin-induced barrier dysfunction show that bacteria cross the epithelium via a transcellular pathway, which is abrogated by treatment with vitamin C [74]. Thus, poor ascorbate status at the gut likely exacerbates barrier dysfunction that increases the translocation of LPS-derived Gram-negative bacteria to potentiate inflammation."

@Kartoffel
​

"Oxygen may play a critical role in gut health. Oxygen gradients decrease steeply from the upper to lower gastrointestinal tract and also increase from the lumen to the more vascularized epithelial layer. Oxygen regulates microbial colonization with more oxygen-tolerant bacteria in the mucosa (e.g. Helicobacter) whereas obligate anaerobes (e.g. Firmicutes) are luminal [86,87]. Oxygen gradients also contribute to microbial biogeography by influencing metabolite production and modulating redox effectors (e.g. nitric oxide, hydrogen sulfide, ROS) of either bacteria or host origin [88]. ROS generated by the intestinal epithelium [89,90] function to exert redox-responsive cell signaling (e.g. thiol redox switches) and maintain gut barrier integrity [91,92]."

"[..]in early-weaned piglets with gut dysbiosis and decreased intestinal ROS-detoxifying capacity, a vitamin C-rich antioxidant cocktail improved intestinal redox status in association with increased proportions of commensal bacteria and decreased pathogenic bacteria [95]."

"A vitamin C-rich functional food also alleviated metabolic endotoxemia and liver steatosis in a rat NAFLD model in association with improved microbiota composition (i.e. greater α-diversity, increased Firmicutes/Bacteroidetes ratio) [96]."

"Further, studies in vitro with an antioxidant cocktail containing vitamin C facilitated the successful culturing of anaerobic protozoa in association with decreasing the oxidationreduction potential (i.e. more reduced environment) and increasing acetate, a short chain fatty acid that is an important energy source for these microorganisms [97]. We therefore posit that greater vitamin C intakes can directly attenuate metabolic endotoxemia in MetS by improving gut barrier function, as well as improving microbial diversity and function."

"Increased levels of circulating LPS have been observed following strenuous aerobic exercise [98]. After exercise, the plasma ascorbate free radical (Asc-) increased, which suggests an increase in oxidative distress. However, in this study, oral vitamin C supplementation (1,000 mg) decreased LPS concentrations and increased plasma ascorbate from 29 to 121 uM. As might be expected, supplementation also increased the plasma Asc- level both before and after exercise. [98]"

"The interactions of antioxidants have been recognized by free radical chemists for decades [99,115]. We previously addressed this question by investigating the turnover kinetics of α-TOH in cigarette smokers; smokers had increased oxidative distress. We found that the disappearance of α-TOH was inversely related to plasma ascorbate levels [83], but could be normalized by vitamin C supplementation [82]. We have now focused on the possibility that α- TOH bioavailability is highly dependent upon adequacy of vitamin C, not only to recycle and maintain α-TOH [99], but also to enhance physiological functions along the gut-liver axis that facilitate trafficking of α-TOH to achieve vitamin E adequacy."

@haidut
​

"Bioavailability [116] is defined as it relates to α-TOH as the extent and rate of α-TOH incorporation into the circulation, which is dependent upon α-TOH absorption, lipoprotein incorporation, trafficking, and lipoprotein-mediated tissue uptake, as well as hepatic catabolism (Figure 3) [117]. Increased inflammation and oxidative damage in association with low vitamin C status in persons with MetS potentiated already poor α-TOH status by limiting α-TOH trafficking along the gut-liver axis [18]."

"Increased oxidative distress results in faster disappearance rates of plasma α-TOH in cigarette smokers [83,121]. Consistent with correlative evidence that low vitamin C status increases the rate of disappearance of α-TOH [83], findings from a randomized placebo-controlled cross-over study demonstrated that vitamin C supplementation (500 mg twice daily; 2-wk) restored the rates of disappearance of α-TOH to levels no different from nonsmoking persons [82]. This observation is consistent with a mechanism by which ascorbate functions as an electron-donor to reduce the α-tocopherol radical (α-TO*) back to α-TOH, the functional form as a donor antioxidant, i.e. it recycles vitamin E [99]."

"Similar to smokers, inadequate vitamin C status in MetS persons could, in part, impair α-TOH status by increasing oxidative α-TOH depletion because biomarkers of oxidative distress and inflammation are higher in MetS persons compared with healthy individuals [18,19,122] (Figure 3). Further, participants with MetS had lower plasma ascorbic acid concentrations despite eating diets with similar amounts of vitamin C as those consumed by healthy subjects for 3 days prior to completing α-TOH pharmacokinetic studies [18]. In those pharmacokinetic studies, α-TOH bioavailability was significantly reduced among MetS persons."

"The paradigm in MetS of decreased α-TOH status is best described by the concept of “physiological inadequacy” and is driven in MetS by impaired trafficking of α-TOH along the gut-liver axis [18]. The challenge to interpret the lower α-TOH bioavailability and slower plasma α-TOH turnover observed in MetS [18] is that α-TOH status is difficult to assess in hyperlipidemic individuals. Because circulating lipoproteins transport α-TOH with other lipids (e.g. triglyceride, cholesterol), elevated blood lipids “trap” α-TOH in the circulation. This process yields apparently “normal” plasma α-TOH concentrations that mask the fact that α-TOH concentrations in target tissues are inadequate, thereby permitting oxidative injury [19,123]. We propose that a urinary vitamin E catabolite, α-CEHC, can be used in conjunction with circulating α-TOH as a more reliable biomarker of α-TOH status, especially among hyperlipidemic persons where even lipidnormalized measures of α-TOH status have limited interpretation [123]."

"Inflammation likely also drives systemic depletion of ascorbate, as shown in sepsis patients [133], who despite receiving 50 or 200 mg still become deficient in vitamin C due to heightened immune responses in septic shock that increase the rate of oxidation vitamin C, resulting in its depletion [134]. Taken together, the available data support the premise that endotoxemia promotes poor vitamin C status and exacerbates inflammation along the gut-liver axis that increases the demand for antioxidant defenses, especially vitamins C and E."​

One of the authors is a known vitamin E researcher:
- Maret G. Traber

Thanks. I haven't really looked into vitamin C in the context of endotoxemia and intestinal health. Do you think that vitamin C is particularly important in this regard? I'm asking because low vitamin status is found for a great variety of vitamins in people with endotoxemia, IBS, CFS, etc, and many studies show that restoring this or that vitamin significantly improves intestinal barrier function. Glycine, niacinamide, thiamine, vitamin K, etc all improve the gut barrier function by partially restoring energy metabolism and antioxidant/oxidant balance. Prolonged intestinal inflammation and metabolic endotoxemia probably cause global/multiple chronic deficiencies over time, including amino acid deficiencies.

 

[Amazoniac]

Thanks. I haven't really looked into vitamin C in the context of endotoxemia and intestinal health. Do you think that vitamin C is particularly important in this regard? I'm asking because low vitamin status is found for a great variety of vitamins in people with endotoxemia, IBS, CFS, etc, and many studies show that restoring this or that vitamin significantly improves intestinal barrier function. Glycine, niacinamide, thiamine, vitamin K, etc all improve the gut barrier function by partially restoring energy metabolism and antioxidant/oxidant balance. Prolonged intestinal inflammation and metabolic endotoxemia probably cause global/multiple chronic deficiencies over time, including amino acid deficiencies.

Yeah, I can't imagine why its needs would not be increased if there's inflammation there and remain elevated until the issue is corrected.

 

[tankasnowgod]

Will is vitamin E when C is depleted from inflammation?

The Relationship Between Vitamin C Status, the Gut-Liver Axis, and Metabolic Syndrome

Their key points:

- "Excess dietary energy provokes gut dysbiosis leading to increased inflammation."
- "Impairments in gut function contribute to metabolic endotoxemia."
- "Endotoxemia depletes vitamin C, which in turn impairs vitamin E trafficking."
- "Higher vitamin C intake can restore gut-liver functions and antioxidant status."​

"Inadequate vitamin C intakes clearly impair vitamin C status [4]; however, ascorbic acid is also depleted systemically by its reaction with hypochlorous acid (bleach), an anti-microbial agent produced by neutrophils [12]. Although no studies have explicitly tested the hypothesis, the objective of this review is to present evidence supporting that poor vitamin C status in MetS is driven by gut inflammation and barrier dysfunction attributed to excess dietary energy consumption [13]. Importantly, impaired gut barrier function in MetS mediates metabolic endotoxemia by increasing the absorption of bacteria and gut-derived endotoxins (e.g. lipopolysaccharide (LPS)) [13,14] while also impairing vitamin C absorption [15]. These inter-related events provoke a vicious cycle, both increasing chronic inflammation and oxidative damage."

"[..]because LPS triggers intestinal and hepatic inflammation, we propose that improved vitamin C status along the gut-liver axis would restore vitamin E trafficking and bioavailability that is otherwise impaired in MetS persons, likely due to their heightened inflammation in association with poor vitamin C status [18,19]."

"Potentially, inadequate vitamin C status in MetS contributes to small intestinal bacterial overgrowth, transcytosis of enteric bacteria, and an elevation of circulating LPS, which elicits a low-grade inflammatory response. By contrast, oral ingestion of large-dose vitamin C supplements results in limited intestinal vitamin C absorption [26], with excess ascorbic acid remaining in the gut lumen where it can potentially exert beneficial effects both on the intestinal cells and microbiota composition and function."

@Roselle525 - it's something we have been considering.
​

"Normally, LPS is absorbed from the intestine bound to the LPS-binding protein attached to chylomicrons [31]. This chylomicron-dependent mechanism protects against TLR4-induced inflammation by directing LPS to the lymphatics instead of the portal stream, sequestering LPS away from circulating white cells by instead delivering it to the liver for detoxification [32]. However, increased LPS absorption is promoted by a high-fat diet that not only increases chylomicron secretion, but also increases gut barrier dysfunction, thereby allowing LPS passage and increasing circulating LPS, which potentiates endotoxemia-associated inflammation [13,33-35]."

"Our assessment of a limited population of relatively healthy adults with MetS shows that, in association with lower vitamin C status, persons with MetS not only have metabolic endotoxemia (unpublished observation; Figure 2) and increased biomarkers of inflammation but also lower α-tocopherol (α-TOH) bioavailability [18,19]. These findings suggest a complex interaction between the antioxidant vitamins and endotoxin-induced inflammation, as well as with other dietary antioxidants [36]. Although causality has yet to be established, hypothetically poor vitamin C status drives metabolic endotoxemia, or conversely heightened inflammation due to endotoxemia depletes systemic vitamin C."

"Endotoxemia may also further impair the already low ascorbate status in MetS because LPS inhibits absorption of ascorbate [15] by decreasing sodium-dependent vitamin C transporters (SVCT-1 and -2) [15,38-40]. Additionally, oxidized ascorbate (i.e. dehydroascorbic acid; DHA) can be taken up by enterocytes via glucose transporters [41,42]. However, when glucose intakes are high, this mechanism has little benefit on vitamin C status because concentrations of DHA are much lower than that of glucose [43,44]. Thus, poor vitamin C status in MetS may not only be the result of low dietary vitamin C intakes [4], which are exacerbated by impaired absorption of either ascorbate or DHA."

"Animal studies support the concept that vitamin C can reduce the sequelae of MetS." "Vitamin C-deficient guinea pigs in response to endotoxemia induction have increased NF-kB responses in association with exaggerated systemic shock and impaired lung phosphatidylcholine biosynthesis [60-62], while dietary vitamin C supplementation attenuates endotoxemia and intestinal barrier defects [62]. Vitamin C-deficient ODS rats also demonstrate increased endotoxemia associated with increased liver inflammation and gut dysfunction [63], increased gastric mucosal lesions [64], acute phase responses [65], inflammatory chemokine and cytokines [66], and cytokine-induced neutrophil chemoattractant-1 (CINC-1) [66]. They also have increased LDL [67], decreased HDL [68] and impaired synthesis of apo-AI [69]. Thus, the association between vitamin C deficiency and the hallmarks of MetS (i.e. gut barrier dysfunction, increased endotoxemia, inflammation, altered lipoproteins) are supported by studies in vitamin C-deficient animals."

@Terma
​

"[..]ascorbate blocks endotoxemia [73]."

"Ascorbate reacts as an antioxidant with hypochlorous acid, an anti-microbial agent that is produced by neutrophils via myeloperoxidase (MPO) [12]. Further, intestinal and circulating neutrophils accumulate high ascorbate levels that function to protect themselves from MPO, which is activated during bacterial phagocytosis [37]. Remarkably, MPO also acts as an “ascorbate peroxidase” that directly consumes ascorbate [78]. Thus, the oxidative distress that is evident in MetS consists not only of non-specific lipid peroxidation that consumes α-TOH [79] to potentially increase the risk for NAFLD [80,81], but is also is a direct consequence of increased inflammatory responses (i.e. MPO) that deplete vitamin C. Further, we have shown that insufficient ascorbate results in the more rapid depletion of α-TOH [82,83]."

"Another potential benefit of increased vitamin C intake is the improvement in barrier function caused by increasing collagen synthesis in the intestine [77]. This proposed mechanism is consistent with ascorbate’s coenzyme function that hydroxylates proline and lysine to cross-link collagen [85]. For example, studies in the T84 human crypt-like epithelial cell line with indomethacin-induced barrier dysfunction show that bacteria cross the epithelium via a transcellular pathway, which is abrogated by treatment with vitamin C [74]. Thus, poor ascorbate status at the gut likely exacerbates barrier dysfunction that increases the translocation of LPS-derived Gram-negative bacteria to potentiate inflammation."

@Kartoffel
​

"Oxygen may play a critical role in gut health. Oxygen gradients decrease steeply from the upper to lower gastrointestinal tract and also increase from the lumen to the more vascularized epithelial layer. Oxygen regulates microbial colonization with more oxygen-tolerant bacteria in the mucosa (e.g. Helicobacter) whereas obligate anaerobes (e.g. Firmicutes) are luminal [86,87]. Oxygen gradients also contribute to microbial biogeography by influencing metabolite production and modulating redox effectors (e.g. nitric oxide, hydrogen sulfide, ROS) of either bacteria or host origin [88]. ROS generated by the intestinal epithelium [89,90] function to exert redox-responsive cell signaling (e.g. thiol redox switches) and maintain gut barrier integrity [91,92]."

"[..]in early-weaned piglets with gut dysbiosis and decreased intestinal ROS-detoxifying capacity, a vitamin C-rich antioxidant cocktail improved intestinal redox status in association with increased proportions of commensal bacteria and decreased pathogenic bacteria [95]."

"A vitamin C-rich functional food also alleviated metabolic endotoxemia and liver steatosis in a rat NAFLD model in association with improved microbiota composition (i.e. greater α-diversity, increased Firmicutes/Bacteroidetes ratio) [96]."

"Further, studies in vitro with an antioxidant cocktail containing vitamin C facilitated the successful culturing of anaerobic protozoa in association with decreasing the oxidationreduction potential (i.e. more reduced environment) and increasing acetate, a short chain fatty acid that is an important energy source for these microorganisms [97]. We therefore posit that greater vitamin C intakes can directly attenuate metabolic endotoxemia in MetS by improving gut barrier function, as well as improving microbial diversity and function."

"Increased levels of circulating LPS have been observed following strenuous aerobic exercise [98]. After exercise, the plasma ascorbate free radical (Asc-) increased, which suggests an increase in oxidative distress. However, in this study, oral vitamin C supplementation (1,000 mg) decreased LPS concentrations and increased plasma ascorbate from 29 to 121 uM. As might be expected, supplementation also increased the plasma Asc- level both before and after exercise. [98]"

"The interactions of antioxidants have been recognized by free radical chemists for decades [99,115]. We previously addressed this question by investigating the turnover kinetics of α-TOH in cigarette smokers; smokers had increased oxidative distress. We found that the disappearance of α-TOH was inversely related to plasma ascorbate levels [83], but could be normalized by vitamin C supplementation [82]. We have now focused on the possibility that α- TOH bioavailability is highly dependent upon adequacy of vitamin C, not only to recycle and maintain α-TOH [99], but also to enhance physiological functions along the gut-liver axis that facilitate trafficking of α-TOH to achieve vitamin E adequacy."

@haidut
​

"Bioavailability [116] is defined as it relates to α-TOH as the extent and rate of α-TOH incorporation into the circulation, which is dependent upon α-TOH absorption, lipoprotein incorporation, trafficking, and lipoprotein-mediated tissue uptake, as well as hepatic catabolism (Figure 3) [117]. Increased inflammation and oxidative damage in association with low vitamin C status in persons with MetS potentiated already poor α-TOH status by limiting α-TOH trafficking along the gut-liver axis [18]."

"Increased oxidative distress results in faster disappearance rates of plasma α-TOH in cigarette smokers [83,121]. Consistent with correlative evidence that low vitamin C status increases the rate of disappearance of α-TOH [83], findings from a randomized placebo-controlled cross-over study demonstrated that vitamin C supplementation (500 mg twice daily; 2-wk) restored the rates of disappearance of α-TOH to levels no different from nonsmoking persons [82]. This observation is consistent with a mechanism by which ascorbate functions as an electron-donor to reduce the α-tocopherol radical (α-TO*) back to α-TOH, the functional form as a donor antioxidant, i.e. it recycles vitamin E [99]."

"Similar to smokers, inadequate vitamin C status in MetS persons could, in part, impair α-TOH status by increasing oxidative α-TOH depletion because biomarkers of oxidative distress and inflammation are higher in MetS persons compared with healthy individuals [18,19,122] (Figure 3). Further, participants with MetS had lower plasma ascorbic acid concentrations despite eating diets with similar amounts of vitamin C as those consumed by healthy subjects for 3 days prior to completing α-TOH pharmacokinetic studies [18]. In those pharmacokinetic studies, α-TOH bioavailability was significantly reduced among MetS persons."

"The paradigm in MetS of decreased α-TOH status is best described by the concept of “physiological inadequacy” and is driven in MetS by impaired trafficking of α-TOH along the gut-liver axis [18]. The challenge to interpret the lower α-TOH bioavailability and slower plasma α-TOH turnover observed in MetS [18] is that α-TOH status is difficult to assess in hyperlipidemic individuals. Because circulating lipoproteins transport α-TOH with other lipids (e.g. triglyceride, cholesterol), elevated blood lipids “trap” α-TOH in the circulation. This process yields apparently “normal” plasma α-TOH concentrations that mask the fact that α-TOH concentrations in target tissues are inadequate, thereby permitting oxidative injury [19,123]. We propose that a urinary vitamin E catabolite, α-CEHC, can be used in conjunction with circulating α-TOH as a more reliable biomarker of α-TOH status, especially among hyperlipidemic persons where even lipidnormalized measures of α-TOH status have limited interpretation [123]."

"Inflammation likely also drives systemic depletion of ascorbate, as shown in sepsis patients [133], who despite receiving 50 or 200 mg still become deficient in vitamin C due to heightened immune responses in septic shock that increase the rate of oxidation vitamin C, resulting in its depletion [134]. Taken together, the available data support the premise that endotoxemia promotes poor vitamin C status and exacerbates inflammation along the gut-liver axis that increases the demand for antioxidant defenses, especially vitamins C and E."​

One of the authors is a known vitamin E researcher:
- Maret G. Traber

Excellent stuff! Nice to see some confirmation that supplemental C can be helpful even if not absorbed into the bloodstream. Makes total sense, especially if gut barrier is in any way compromised.

When I was getting de-ironed, I made sure to take supplemental E while doing it, thinking that my high iron stores had depleted antioxidants. Nice to see more confirmation of that. I believe that is one thing that is shown with iron lowering and frequent blood donors, that anti-oxidant status improves over time, even if no additional supplementation is taken.

 

[Makrosky]

What a barbaric study. That proves nothing. No one is shoving vitamin C up their vagina! And there are studies showing it can increase progesterone so this wasn't conclusive on how it effects hormone levels at all. Not to mention there are many many 'vitamin C babies' in a large orthomolecular group I am in. Some have said what an easy pregnancy and delivery it was as compared to other babies they had.

I just took 8 grams this morning. No scalp itch.

Janelle you take 8 grams at once? I thought you cannot absorv more than 1 gram every hour or something like that.

 

[InChristAlone]

Janelle you take 8 grams at once? I thought you cannot absorv more than 1 gram every hour or something like that.

Yeah 8 grams usually doesn't cause loose stool for me but it can.

 

[Makrosky]

Yeah 8 grams usually doesn't cause loose stool for me but it can.

But are you aware you might be absorving only 1/8 of the ammount?

 

[InChristAlone]

But are you aware you might be absorving only 1/8 of the ammount?

I don't know I think the body can absorb quite a bit more than that, it might not be using all of it though, but it's not bad for the kidneys. We argued on here quite a bit if it's better to do small doses more frequently and it may be but I have bad teeth so I just don't want to chance my mouth being bathed in acid so frequent. Unless I put it in a capsule. I may still try doing that. Just hard to be motivated since I still see a lot of benefits from a bolus dose. I don't like taking too much later in the day either as it definitely gives energy.

 

[Makrosky]

I don't know I think the body can absorb quite a bit more than that, it might not be using all of it though, but it's not bad for the kidneys. We argued on here quite a bit if it's better to do small doses more frequently and it may be but I have bad teeth so I just don't want to chance my mouth being bathed in acid so frequent. Unless I put it in a capsule. I may still try doing that. Just hard to be motivated since I still see a lot of benefits from a bolus dose. I don't like taking too much later in the day either as it definitely gives energy.

Ok!

 

[HealthisWealth]

I don't know I think the body can absorb quite a bit more than that, it might not be using all of it though, but it's not bad for the kidneys. We argued on here quite a bit if it's better to do small doses more frequently and it may be but I have bad teeth so I just don't want to chance my mouth being bathed in acid so frequent. Unless I put it in a capsule. I may still try doing that. Just hard to be motivated since I still see a lot of benefits from a bolus dose. I don't like taking too much later in the day either as it definitely gives energy.

Hi janelle. I have been using ascorbic acid now. And its true it gives energy so best to take it in the morning. I just want to know about the kidney causing it to have stones?

 

[InChristAlone]

Hi janelle. I have been using ascorbic acid now. And its true it gives energy so best to take it in the morning. I just want to know about the kidney causing it to have stones?

Some people are more susceptible to kidney stones, but I haven't heard of anyone who wouldn't otherwise get them all of sudden get them because of vitamin C. Some think if they do pass one while taking it that maybe it was helping to expel it, but you'd have to do more research. I have been on 4 grams for over two years sometimes more sometimes less and haven't had any kidney problems.

 

[tankasnowgod]

Hi janelle. I have been using ascorbic acid now. And its true it gives energy so best to take it in the morning. I just want to know about the kidney causing it to have stones?

This was Dr. Cathcart's talking about the Kidney Stone issue with Vitamin C, and he used large doses of C in his practice-

 

[Mossy]

This was Dr. Cathcart's talking about the Kidney Stone issue with Vitamin C, and he used large doses of C in his practice-

I jumped right in after watching the other video with him. I have light flu-like symptoms and bad congestion and was hoping this would knock it out. I had high hopes, as my mother was preaching mega-C doses since I was a child. Well, after 18 grams in a 24 hour period I am no better. I realize that Dr. Cathcart says to keep going to go into the “unsick” state, but my congestion got worse, and I didn’t want to risk prolongong it or doing damage to my body. I had what felt like a severe strain in my lower throat, very top chest area, when coughing in the morning. That has subsided, but I’m wondering if I’m having an allergic reaction to the sodium ascorbate, or maybe I didn’t drink enough liquids. I’m still taking C, just not mega doses.

EDIT: I forgot to add that Dr. Cathcart does mention some people’s stomach can’t take all the acid and that they need to solve that first. Maybe the pain was acid reflux on the esophogus.

 

[tankasnowgod]

I jumped right in after watching the other video with him. I have light flu-like symptoms and bad congestion and was hoping this would knock it out. I had high hopes, as my mother was preaching mega-C doses since I was a child. Well, after 18 grams in a 24 hour period I am no better. I realize that Dr. Cathcart says to keep going to go into the “unsick” state, but my congestion got worse, and I didn’t want to risk prolongong it or doing damage to my body. I had what felt like a severe strain in my lower throat, very top chest area, when coughing in the morning. That has subsided, but I’m wondering if I’m having an allergic reaction to the sodium ascorbate, or maybe I didn’t drink enough liquids. I’m still taking C, just not mega doses.

EDIT: I forgot to add that Dr. Cathcart does mention some people’s stomach can’t take all the acid and that they need to solve that first. Maybe the pain was acid reflux on the esophogus.

I have knocked colds out, but they were at the onset of the cold. If you have been experiencing those flu like symptoms for a few days, it might be a different matter. Last time I did, I used 23 grams in a five hour period, FWIW.

 

[Mossy]

I have knocked colds out, but they were at the onset of the cold. If you have been experiencing those flu like symptoms for a few days, it might be a different matter. Last time I did, I used 23 grams in a five hour period, FWIW.

Yeah, that was a motivator for me. I was hoping I’d get the same results. I’ll play around with doses as my body can handle it. Thanks.

 

[HealthisWealth]

@tankasnowgod thanks for the video

@sugarbabe how do you figure out the correct ascorbic acid dosage? I remember before i was told if it makes you fart and have a feeling of having a loose bowel?