Vitamin C alleviates LPS-induced cognitive impairment in mice by suppressing neuroinflammation

Int Immunopharmacol. 2018 Dec;65:438-447. doi: 10.1016/j.intimp.2018.10.020. Epub 2018 Oct 30.
Vitamin C alleviates LPS-induced cognitive impairment in mice by suppressing neuroinflammation and oxidative stress.
Zhang XY1, Xu ZP1, Wang W2, Cao JB1, Fu Q1, Zhao WX1, Li Y1, Huo XL1, Zhang LM3, Li YF3, Mi WD4.
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Neuroinflammation is believed to be one of the primary causes of cognitive impairment. Previous studies showed that the antioxidant vitamin C (Vit C) performs many beneficial functions such as immunostimulant and anti-inflammatory actions, but its role in inflammatory cognitive impairment is unclear. In the current study, we investigated the effect and possible mechanism of action of Vit C in lipopolysaccharide (LPS)-induced cognitive impairment. Intracerebroventricular LPS-induced memory impairment was used as the model for neuroinflammatory cognitive dysfunction. Vit C was administered by intracerebroventricular microinjection 30 min prior to LPS exposure. It was found that Vit C significantly protected animals from LPS-induced memory impairment as evidenced by improved performance in the Morris water maze and novel object recognition tests without changes in spontaneous locomotor activity. Vit C pretreatment inhibited the activation of microglia and the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, Vit C pretreatment markedly decreased the malondialdehyde (MDA) level, increased superoxide dismutase (SOD) activity, and modulated the Bax/Bcl-2 ratio and p-p38 MAPK activation in the hippocampus of LPS-treated mice. Together, these results suggest that vitamin Cpretreatment could protect mice from LPS-induced cognitive impairment, possibly through the modulation of oxidative stress and inflammatory responses.
Copyright © 2018. Published by Elsevier B.V.
Apoptosis; Memory impairment; Neuroinflammation; Oxidative stress; Vitamin C
PMID: 30388518 DOI: 10.1016/j.intimp.2018.10.020


Senior Member
United States, New Hampshire
You don't already inject vitamin C straight into your brain? ;)
Sounds like something we all should be doing!:rofl: This study has made me think about increasing my vitamin c intake though.

I haven't had a flu-like flare in 3-4 months now. The other day I looked at my calendar to see what changes in supps I made back then. The only significant change I made was to go from 2 to 4 grams of epa/dha a day.

Epa/dha have been found to decrease neuro-inflammation. I can't help but think that could be why I haven't had a flu-like flare in 3-4 months now. I wonder if the vitamin c would work synergistically with the omega 3's?
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Probably that's why vit C is one of the "detox" remedies.. but LPS by itself is not an 100% evil, for example endotoxin injections were used to treat syphilis(some other infections too) and in general LPS turns immune system up a bit:

Usefulness of oral administration of lipopolysaccharide for disease prevention through the induction of priming in macrophages
Coley's toxin has been used as an immunotherapy in patients with cancer since 1891, and this practice is continued even today because of positive experience gained from more than 120 yearsn of use. Coley's toxin contains a mixture of dead Serratia marcescens and Streptococcus pyogenes bacteria and is known as a LPS-containing therapeutic agent (17).
Considering the purposiveness of the LPS, we believe that LPS may be regarded as a micronutrient with some medicinal properties for the human body rather than as an endotoxin. For example, epidemiological studies show that LPS is inversely correlated with risk of allergic disease (hygiene hypothesis) (23). The knockout of the gene of the LPS receptor in mice results in low resistance to infection (24). Moreover, the amount of LPS in various foods indicates that some herbal Chinese medicines contain a few tens of micrograms of LPS per gram of dry weight (8), whereas health foods contain several micrograms. These data suggest that ingestion of a certain amount of LPS may be important for health maintenance.
We have studied the preventative and curative effects on various diseases of oral administration of Pantoea agglomerans LPS, originally isolated from wheat flour. We observed several effects, such as protection from infectious diseases [bacterial and parasitic (toxoplasmosis)], improvement of diabetes and lipid metabolism (14), antiallergic properties in atopic dermatitis (13), an infection prophylaxis effect (25), and beneficial effects in cancer (26). LPS performs an important function in regulation of intestinal bacterial flora through the induction of bactericidal peptides (27). After oral administration, LPS is delivered to Paneth cells in intestinal crypts and induces production of bactericidal peptides defensins, such as regenerating islet-derived protein 3 gamma (28) and cryptdin-4 (29). According to the report of Masuda et al., cryptdin-4 has the ability to control the growth of pathogenic bacteria in the intestine (29).
In a model of chronic stress based on daily dexamethasone injection in chicken, antibody production against a Salmonella vaccine was significantly decreased. Oral administration of P. agglomerans LPS improved the antibody titer against Salmonella in this chronic stress model (31). It was also shown that oral administration of LPS protects against steroidal withering of immune system organs: the spleen and bursa. These results indicate that oral administration of LPS saves immune cells from death caused by several types of stress.
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Conclusion – Macrophages and LPS for Maintaining Health

Macrophages recognize and eliminate oxidized lipids, denatured proteins, advanced glycation end-products, and dead cells. These are the true causative agents of chronic inflammation, which can lead to several diseases such as diabetes, arteriosclerosis, cancer, allergy, and dementia. As mentioned above, the essential role of macrophages in health maintenance is mainly believed to be the removal of waste products from the body. In accordance with this concept, we believe that a new paradigm should be adopted for health maintenance. For example, an outbreak of a disease may be the result of suppression of macrophage function that ensures elimination of waste products.


Senior Member
it took me a long time to figure out that corn is a trigger, and that corn is in A LOT of stuff. most vitamin c products are derived from vitamin c.

I take a vitamin c derived from tapioca and it's one of my few "every day" supplements. It breaks down histamine, which is a problem for many cfs'ers.... the one I take is Ecological Formulas, and it's labeled "from tapioca"

cc: ljimbo423