What are the side effects of high-dose intravenous vitamin C? How does it differ from oral vitamin C intake? Get the answers to these questions and more in this comprehensive article.

Understanding Intravenous Vitamin C Therapy

Intravenous (IV) vitamin C therapy has gained significant attention in recent years as a complementary approach to treating various health conditions. Unlike oral vitamin C supplementation, where the body tightly controls absorption and excretion, IV administration bypasses these regulatory mechanisms, allowing for much higher concentrations of vitamin C to be delivered directly into the bloodstream.

Potential Side Effects of High-Dose IV Vitamin C

While IV vitamin C is generally well-tolerated, there are a few potential side effects to be aware of:

Rare but Serious Complications

In extremely rare cases, a single high dose (10 grams) of IV vitamin C has been reported to cause necrosis, hemorrhage, and subsequent death. This is why healthcare providers typically start with smaller doses and gradually increase the amount as needed.

Kidney-Related Concerns

High-dose IV vitamin C can also lead to acute oxalate nephropathy, particularly in patients with pre-existing kidney issues or impaired renal function. Careful monitoring of kidney health is essential, especially with higher-dose infusions.

Hemolysis and G6PD Deficiency

Patients with a rare genetic condition called glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis (red blood cell destruction) when receiving IV vitamin C. Screening for this condition is recommended before initiating treatment.

Local Infusion Site Effects

Localized pain at the infusion site can occur if the infusion rate is too high or the pH of the solution is too low. This can be easily addressed by adjusting the infusion rate or formula.

Electrolyte Imbalances

IV vitamin C may temporarily decrease levels of certain electrolytes, such as calcium, chloride, and potassium, which can cause symptoms like shakiness or aches. Adjusting the formula to include these electrolytes can help mitigate this issue.

Fluid-Related Concerns

The large volume of fluid used to deliver IV vitamin C can be problematic for individuals with conditions like congestive heart failure, ascites, edema, or pleural effusion. These patients may require a more tailored protocol to manage the increased fluid load.

Temporary Blood Sugar Fluctuations

IV vitamin C can have a temporary dehydrating effect, which may cause a temporary lowering of blood sugar levels. Proper hydration and nourishment are important before and after infusions.

Comparison to Oral Vitamin C Intake

The key difference between oral and IV vitamin C is the way the body handles the nutrient. Oral vitamin C is tightly regulated by the body, with the kidneys and bowels quickly eliminating any excess. In contrast, IV vitamin C bypasses these regulatory mechanisms, allowing for much higher blood concentrations to be achieved.

Oral Vitamin C Limitations

Even by taking up to 18,000 mg of oral vitamin C per day, the blood levels do not exceed 0.2 mM/L. In comparison, a 2,000 mg IV injection can produce blood levels up to 70 times higher, reaching 3 mM/L.

Safety Profile of IV Vitamin C

Despite the potential side effects, IV vitamin C has a relatively good safety profile. A 2010 study evaluating the use of IV vitamin C among practitioners found that only minor side effects, such as lethargy, changes in mental status, and vein irritation, were reported, and these were easily corrected.

The Role of IV Vitamin C in Healthcare

IV vitamin C therapy is being explored as a complementary approach to support the immune system, address potential vitamin C deficiencies, and potentially improve outcomes in various health conditions. While more research is needed, the available evidence suggests that IV vitamin C can be a safe and effective treatment option when administered under the guidance of healthcare professionals.

Conclusion

High-dose IV vitamin C therapy is a powerful tool that can deliver much higher concentrations of the nutrient directly into the bloodstream, potentially offering various health benefits. However, it is important to be aware of the potential side effects and to work closely with healthcare providers to ensure the safe and effective use of this treatment approach.

Intravenous Vitamin C – The Cocktail

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Intravenous Vitamin C – The Cocktaillemmo-admin2022-09-14T19:46:26+00:00

Vitamin C is an important nutrient that may be low or deficient when the body is burdened with disease.

Vitamin C deficiency is reported to occur more frequently in patients with chronic disease, major depression, in hospitalized patients, post-surgical patients, radiation to the gastrointestinal tract, history of malabsorption, treatment with chemotherapy having intestinal or mucosal side effects, slow wound healing, or infection.

Symptoms of vitamin C deficiency include fatigue, myalgia, loss of appetite, weakness, poor wound healing, and edema or swelling in the lower extremities (i.e. legs, thighs, feet).

Vitamin C has important roles in supporting the immune system and decreasing inflammation.

Abnormal cells respond very differently to vitamin C than when compared to the body’s normal cells when applied by intravenous injection. For example, such abnormal cells makes a rather rapid and sustained increase in hydrogen peroxide in response to vitamin C which results in a “rusting-effect” known as oxidative damage which damages or kills such cells. Normal or healthy cells do not respond this way with vitamin C intravenously.

Supportive ingredients alongside the vitamin C, to potentially address other deficiencies , may be considered to assist the body to further help harness the immune-system.

It is for some of the above reasons why vitamin C may improve quality of life and survival.

Further information from the National Institutes of Health (NIH)

and Current Oncology

Precautions: 

The negative side effects of vitamin C IV are rare.  However, there are concerns and potential side effects to be considered:

• Although it has been reported only once in the literature (Scot Med J 1979;24:151), necrosis, hemorrhage, and subsequent death after a single intravenous 10 gram dose of vitamin C should be the highest priority for safety. This is why smaller doses are typically used initially

• Another report described acute oxalate nephropathy in a patient with bilateral ureteric obstruction and renal insufficiency who received 60 gram IVC. Consequently, the kidneys need to be working well enough before beginning and especially with higher dose infusions.

• A rare hemolysis can occur in patients with a red cell glucose-6-phosphate dehydrogenase deficiency (G6PD) and so this may be screened.

• Localized pain at the infusion site can occur if the infusion rate is too high or the pH too low.  This is easily corrected by either slowing the rate or adjusting the formula.

• Vitamin C may decrease the levels of calcium, chloride, and potassium and as a consequence some patients may experience shakiness or ache. This may be assisted by adjusting the formula with those ingredients.

• Given the amount of fluid and sodium that is used as the carrier for vitamin C, any condition which could be affected by the increased fluid load (i. e. congestive heart failure, ascites, edema, pleural effusion, etc.) needs to be monitored more closely and a tailored protocol given accordingly.

• IVC may be dehydrating and cause a temporary lowering of blood sugar, and so proper hydration and nourishment needs to be emphasized prior

• It may falsely read as very high  blood sugar if measured shortly after an infusion (i.e. vitamin C and glucose are almost identical in structure)

• As with any intravenous injection, infiltration or vein irritation is possible

Basic Facts – Intravenous vs. Oral

• Vitamin C levels in the body are tightly controlled by the bowels and the kidney’s (i.e. the body gets rid of it quickly)

• Even by taking up to 18000mg per day orally in divided doses throughout the day, the blood levels do not change and do not exceed 0. 2 mMol/L

• Intravenous vitamin C bypasses the tight control by the body leading to a 70-fold higher blood levels with only a 2000mg injection

• A simple injection of 5000mg of vitamin C produces a blood value of 3mMol/L and the research has shown that you can kill abnormal cells in the laboratory with values between 0.5 to 3mMol/L

Safety of Intravenous Vitamin C:

A 2010 study evaluating the use of vitamin C amongst practitioners revealed, after calculating over 750,000 yearly sales and estimated yearly doses of over 350,000 in 2008, and after evaluating over 9000 patients,  only minor side-effects were noted that  included lethargy/fatigue, change in mental status, and vein irriation.  Clinically, if these effects occur they are temporary and easily corrected.

Padayatty SJ et a. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects.   PLoS One. 2010 Jul 7;5(7):e11414.

Overall Roles of Vitamin C:

• Correction of possible vitamin C deficiency (i.e. fatigue, bleeding)

• Immune-modulation / Immune system support

• White blood cell support (they have 10-30x higher levels than the blood)

• Wound healing support

• Cytotoxic (i.e. stimulates hydrogen peroxide production)

• Anti-angiogenesis

• Hyaluronidase inhibition

• Anti-inflammatory

• Anti-stress and Anti-depressant properties

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High-Dose Intravenous Vitamin C in Cancer Care

A new intravenous vitamin C (IVC) clinical trial—and a call for physicians providing IVC to report cases of exceptional responses to help better focus future studies.

Reference

Hoffer LJ, Robitaille L, Zakarian R, et al. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS ONE. 2015;10(4):e0120228. 

Study Objectives

The study aimed to 

1. determine the safety and tolerability of 1.5 g/kg intravenous vitamin C (IVC) over 90-120 minutes given 2-3 times per week to cancer patients during the course of chemotherapy including documentation of side effects and toxicity;
2. determine pharmacokinetics by measuring plasma vitamin C and urinary oxalic acid before, during, and after treatment with IVC and chemotherapy; 
3. identify any cancer types and treatments that might be favorable to combine with IVC if possible; and
4. measure quality of life (QoL) and mood monthly throughout the study.

Design 

Single dose Phase IIA pilot study 

Participants 

Oncology patients ages 47 to 76 were referred from within a medical university–affiliated cancer center and were eligible if they had an Eastern Co-operative Oncology Group (ECOG) status 0-1, a CT and staging workup within the 4 weeks of the first IVC treatment on protocol, normal red blood cell glucose 6 phosphate dehydrogenase (G6PD) activity, serum creatinine ≤175 µmol/L, and the judgment of their treating oncologist that standard of care or off-label cytotoxic chemotherapy offered less than a 33% likelihood of an objective clinical response. The study evaluated 31 people, enrolled 16, analyzed 12, and described 14 (7 males, 7 females).

Study Parameters Assessed

CT scan of chest, abdomen, and pelvis performed 4 weeks before treatment and approximately every second chemotherapy cycle with assessment for any response using Response Evaluation Criteria in Solid Tumors (RECIST 1.0).

• The following were measured at study entry and every 4 weeks:
• Tumor markers
• Complete blood count (CBC)
• Metabolic panel
• C-reactive protein (CRP)
• Physical exam
• Coagulation profile

The following were measured at baseline, at 2 weeks, and then monthly:

• Functional Assessment of Cancer Therapy-General (FACT-G) quality of life questionnaire scores; range from 1 to 108
• Profile Mood States-B questionnaire giving Total Mood disturbance score; range from -20 to 100

Less than 7 days prior to first chemotherapy dose, plasma vitamin C levels and urinary oxalic acid were measured during and after the administration of 0. 6 g/kg IVC given over 90 minutes. The same was performed again 3 days after chemotherapy administration.

Adverse events were evaluated using National Cancer Institute clinical criteria 3.0.

Primary Outcome Measures

Safety and tolerability of 1.5 g/kg IVC given concurrent to chemotherapy regimens (although not given on the same day) in a heterogeneous advanced disease cancer population via descriptive analysis using quality of life and mood questionnaires and individual case synopsis.

Pre- and post-chemotherapy pharmacokinetics of IVC in humans with advanced cancer via measurement of plasma IVC and urinary oxalate levels before, during, and after treatment. 

Key Findings

IVC was nontoxic for all participants. Side effects of thirst and increased urinary flow were common symptoms during all IVC infusions. Other side effects included nausea and vomiting, unpleasant fluttering sensation, chills, headaches, and a rumbling feeling in the abdomen. One patient experienced increased lower extremity edema. One patient reported a mentally hazy feeling on the day after infusion.

Mean baseline plasma vitamin C concentrations changed from 66.4±74.9 µmol/L before IVC and chemotherapy was initiated to 131.6±102.0 µmol/L after treatment (P<0.031). Total urinary excretion profiles before chemotherapy was initiated (149±49.3) were higher than after (133±40.0), suggesting a short-term tissue retention of vitamin C after chemotherapy (P<0.099) with no significant increase in total urinary oxalic acid excretion (P<0.850).

Three patients with different types of cancer experienced unexpected transient stable disease, increased energy, and functional improvement.

Practice Implications

Pilot studies should provide a clear list of aims and objectives within a formal framework to encourage methodological rigor, produce a work that is scientifically valid and publishable, and lead to higher-quality RCTs. ¹

For our purposes as integrative providers, we hope that an IVC pilot will help us focus efforts and find key reasons larger studies should move forward. In vitro and preclinical data report IVC to have pro-oxidative and antitumor effects.^2-4 Human clinical trials have not found clear-cut antitumor response but have achieved high blood millimolar concentrations of ascorbate in humans (10+ mmol/L) similar to in vitro (5 mmol/L) and preclinical models (10 mmol/L) that have demonstrated antitumor effects. At this point human IVC clinical trials collectively suggest that improved quality of life and reduction in symptoms of disease and/or side effects of cancer treatment may be attributed to treatment with IVC. ^5-9

Although this pilot study is based on a non-statistically representative population, and therefore is limited in practice implications, it does raise some points to consider.

This study is one of a growing body of studies finding safety and tolerability of IVC in patients with advanced disease receiving standard chemotherapy regimens. ^9-14 The study describes 14 cases of people with different tumor types (6 colorectal, 2 lung, 1 cervical, 1 breast, 1 ovarian, 1 bladder, 1 tonsil, 1 biliary) who receive IVC 2-3 times weekly during treatment with chemotherapy regimens where the oncologist determines there’s less than 33% chance the chemo may have efficacy. 

The first author of this study published another important Phase I pilot study in 2008 that reported IVC is safe and well-tolerated in humans with advanced malignancy and established a safe and tolerated dose of 1.5 g/kg given 3 times weekly.¹¹ The 2008 Hoffer study also described that patients receiving 1.5 g/kg excreted a mean 81.3±18.8 mg of oxalic acid (during and over the 6 h after infusion) before returning to baseline. Oxalic acid excretion normally ranges from 10 to 60 mg/24 h. Thus it was determined that a transient rise with subsequent return to normal shortly after IVC was not a threat to patients with normal kidney function. The study also found that patients reliably excreted 25% of the vitamin C during the infusions and established that time-blood plasma vitamin C concentration were relative and predictable according to dose of IVC.

The current study continues this work. The dose and frequency of IVC given is 1.5 g/kg administered 2-3 times weekly, though in this study it is given to patients receiving concurrent chemotherapy (not on the same day). It also reproduces similar, statistically analyzed minimal and transient rise in oxalic acid excretion during and after IVC, as well as a reduction in total ascorbate excreted after chemotherapy. It is plausible to consider that during pro-oxidant therapies, antioxidant blood levels may decrease. Body stores of vitamin C may be in flux, hence less may be excreted. Other investigators have conducted studies reporting that when given the same doses of IVC, patients with metastatic disease excrete less ascorbate compared to those with local disease. ¹⁵ This phenomenon has been well-documented in other disease and chronic inflammatory states, as well as in smokers.^16-18 It is thought that the higher state of inflammation in metastatic disease states consumes more antioxidants. That said, there is much concern over whether antioxidant vitamin C interferes with chemotherapy. Conventional oncology providers caution that in patients with known curative potential from conventional means, the addition of IVC therapy is an unknown and poses an undefined risk of interfering with the benefits of treatment until outcome studies prove otherwise. This is certainly something to further explore in well-designed studies. Most of the high-dose IVC studies to date, including the Hoffer 2015 study and others referenced previously, are designed to test safety and benefits with advanced disease (eg, improving quality of life, stabilizing disease trajectory, lessening side effects of conventional therapies).

One interesting component of this study is that the authors report 2 cases of hypovitaminosis C out of 14 cases evaluated during enrollment. The odds of this occurring in cancer patients compared to the general population are higher. One observational study found 6 cases of scurvy in 3,723 consecutive patients treated for noncancerous conditions in a hospital emergency room; 6 cases of scurvy were found in 219 patients with cancer who were consecutively treated during the same timeframe.¹⁹ Informed clinicians should watch for signs and symptoms of hypovitaminosis and nutrient deficiency in patients with cancer. These symptoms may be commingled with signs of disease processes and side effects of standard antineoplastic treatments.

Cancer patients are known to have hypovitaminosis more frequently than healthy populations^19-24, for a variety of reasons, such as physiologic stresses associated with disease processes, impaired oral intake, a history of surgery or radiation affecting absorptive digestive surfaces, and the catabolic effects of antineoplastic therapy. 

Patients in this study also reported side effects of IVC—some of which the authors attribute to the high osmolarity and cooler than ambient temperature and/or sodium load of the IVC infusate. The authors state some of the side effects were reduced or eliminated with slowing the rate of the IVC infusion, reducing the total IVC dose, and/or letting the infusion solution come to room temperature before administration. It’s also notable that this study used sterile water and vitamin C for infusion vs sterile water, vitamin C, plus mineral additives. 

Hoffer reports that adverse events or side effects may occur for patients using IVC unless safeguards and the above mitigating procedures are used. Appropriate screening as part of the methodology of this study includes G6PD testing of each patient prior to IVC administration and assuring adequate kidney function, since vitamin C is primarily cleared by the renal system. No further screening for safety with IVC is discussed in the methods section of the paper. However, other investigators have listed potential contraindications or exclusions in methodology such as serum glucose >300 mg/dL, hypercalcemia or hyper-oxaluria, metal storage diseases, and iron overload. This study reiterated the previous caution that finger stick glucose could be falsely abnormal and should be avoided for 12 hours after IVC.⁸

This study adds to the safety literature on IVC in cancer care. It also provides objective, concise descriptive summaries of 14 cases of people with advanced cancer who received IVC adjunctive to standard of care chemotherapy. In a way, this brings forward the work of Cameron and Pauling, who reported on the treatment of advanced stage cancer patients who did not have the option of salvage therapies at that time period and were reported to have had improved quality of life and survival with use of IVC and oral vitamin C.^25-26

Though this prospective study by Hoffer et al is considered more methodologically rigorous in our current paradigm, the number of cases is too small to get an idea of what IVC might offer for patients in the day-to-day difficulties of managing disease and standard of care treatment. This study and the 14 case synopses, in which 3 people are reported to have longer than anticipated periods of stable disease deemed unlikely to result from chemotherapy alone, seems to convey rather more side effects from IVC with equal weighting to any benefits. In fact the study reports some rather significant-sounding side effects from high-dose IVC, as well as beneficial effects reported by patients. The QoL and mood questionnaires did not report any trends. 

Hoffer relates that “despite its biological and clinical plausibility, [IVC] is ignored by conventional cancer investigators and funding agencies” and suggests that there may be value in an individual case-centered evaluation strategy such as “discovery in clinical practice,” which has been advocated as a means to discovering new indications for conventional drug therapies. The authors state that integrative cancer therapists prescribe IVC widely without collectively reporting clinical data that is normally gathered as important in cancer drug development.  

Hoffer concludes “if carried out in sufficient numbers, simple studies like this could identify specific clusters of cancer type, IVC, and chemotherapy regimens in which unexpectedly beneficial outcomes or exceptional responses occur frequently enough to justify focused clinical trials.” This brings to mind the work being done in gynecologic cancers by Jeanne Drisko et al as was reported in the Ma 2014 study previously referenced. In my experience in working primarily with pancreatic cancer patients for several years in an integrative cancer hospital in which patients routinely received IVC as part of their care, this population is also of interest for further exploration in well-designed clinical trials. Perhaps IVC could be used adjunctively earlier in diagnosis and with first- and second-line regimens to test whether IVC combined with chemotherapy can improve survival outcomes vs standard therapies alone.

Many of us have seen through clinical experience that IVC appears to help quality of life and/or improve tolerability of standard chemotherapy regimens. Some of our patients have significant alteration in disease status and unusually favorable results when receiving IVC therapy alone or in addition to standard of care cancer treatment. If we can work to document cases like these via case reports or series and do the hard work of designing small clinical trials to test its benefits, as Hoffer’s 2015 IVC study advocates, we’ll improve our ability to learn about IVC and other therapies while helping create a new paradigm of integrative cancer care. 

Vitamin Daily Limits and Overdose Statuses

News and Promotions Vitamin Daily Limits and Overdose Statuses

Overdose of vitamins A, D, E, C and others

Vitamins are vital substances whose deficiency causes disease. However, thoughtlessly exceeding dosages can cause an overdose. This article discusses the consequences of taking high doses of various vitamins and, where known, indicates the maximum allowable daily intake.

Vitamin A

Vitamin A overdose is quite rare due to a number of reasons:

• relatively inefficient intestinal metabolism of provitamin A;
• unidirectional oxidation of retinoic acid, which is rapidly catabolized and excreted from the body;
• high retinol binding capacity of CRBP;
• storage of vitamin A in the liver.

Therefore, the doses required to develop the toxic effects of vitamin A are quite large (the first signs of hypervitaminosis occur when plasma retinol levels are above 3 µmol/l).

The main symptoms of vitamin A overdose: drowsiness, irritability, headache, abdominal pain, nausea, vomiting, convulsions. In chronic poisoning, hepatosplenomegaly, dry skin, hyperpigmentation, alopecia of eyelashes and eyebrows, brittle nails, pain in bones and joints, and sometimes excessive growth of bone tissue develop. In addition, the teratogenicity of one of the vitamin A metabolites has been proven, therefore, after an overdose, it is recommended to use contraception during one menstrual cycle.

The beta-carotene found in vegetables, such as carrots, is slowly converted to vitamin A in the body. Consuming large amounts of these vegetables can lead to carotenoses (yellowing of the skin, especially on the palms and soles), but does not appear to causes any toxic effects.

The maximum allowed intake of vitamin A for adults is 3000 mcg/day [1, pp. 153-156].

Figure 1. Vitamin A concentration versus clinical symptoms

Vitamin D

Hypervitaminosis D is associated primarily with the consumption of high doses of vitamin-containing dietary supplements, since there are no reported cases of hypervitaminosis associated with excessive exposure to sunlight.

In young children, hypervitaminosis D develops when taking 40,000 IU/day for 1-4 months, in adults – more than 100,000 IU/day. It is characterized by the development of hypercalcemia as a result of increased intestinal absorption and resorption of calcium in the bones and a concomitant decrease in serum parathyroid hormone levels. In case of vitamin D poisoning, anorexia, nausea, vomiting, diarrhea, polyuria, headache, weakness, less often – arrhythmias, convulsions occur. In addition, calcification develops – calcium deposition in soft tissues (heart and blood vessels, kidneys, organs of the respiratory system, and others), and urolithiasis. The risk is especially increased when taking vitamin D and calcium at the same time. An overdose of vitamin D during pregnancy causes an increase in the frequency of spontaneous abortions, as well as the development of fetal hypercalcemia, which is manifested by intrauterine growth retardation (hypotrophy, dysplasia), aortic valve stenosis, fibroelastosis, and dysplasia of the tooth germs [1, pp. 202-204].

Figure 2. Recommended Upper Intakes for Vitamin D

Vitamin E

Vitamin E is considered one of the least toxic vitamins. Daily doses up to 400 IU are considered harmless, and high doses (up to 3200 IU) when taken orally do not cause persistent side effects. However, there are anecdotal reports of adverse effects in people consuming up to 1,000 IU of vitamin E per day. These side effects include headache, fatigue, nausea, double vision, muscle weakness, mild creatinuria, and dyspepsia. In addition, when taking high doses of vitamin E, there is a risk of impaired absorption and metabolism of other fat-soluble vitamins (A, D and K), which leads to changes in bone mineralization, the development of coagulopathy (important for patients receiving anticoagulants), a decrease in the concentration of vitamin A in liver. Premature infants given mega-doses of vitamin E may develop necrotizing enterocolitis and sepsis.

It is practically impossible to achieve a high intake of vitamin E from food, so overdose is mainly associated with a high intake of biological additives [1, p. 239, 2].

Figure 3. Tolerable upper intake levels for vitamin E

Vitamin C

No significant side effects of ascorbic acid (vitamin C) have been identified. High doses of the vitamin both orally and intravenously do not cause the development of significant side effects. However, there are reports of gastrointestinal disturbances and diarrhea with megadoses of vitamin C. Hypervitaminosis C is also associated with the risk of developing oxaluria (oxalate in the urine) and the potential for urolithiasis, since oxalate is the main metabolite of ascorbic acid. In addition, vitamin C supplementation may enhance enteral absorption of iron and subsequent accumulation in tissues, so supplements containing this vitamin are not recommended for patients with hemochromatosis. On the other hand, despite the possibility of these side effects, the risk of their development, apparently, is small.

Other hypothesized effects caused by excess vitamin C intake, such as: uricosuria (increased uric acid in the urine), vitamin B12 deficiency, “rebound scurvy” (increased vitamin C catabolism and symptoms of deficiency with reduced dosage) have not been confirmed in studies [ 1, pp. 292-293; 3].

Figure 3. Tolerable Upper Intakes for Vitamin C

Vitamin B1

Vitamin B1 (thiamine) is generally well tolerated at therapeutic doses (up to 100 mg/day), but allergic reactions are not uncommon, including inhaled substances (injectable forms of vitamin B1 are very volatile). In case of an overdose, it can inhibit the activity of cholinesterase (curare-like signs) and histaminase (allergic reactions and anaphylactic shock). Vitamin B1 poisoning is accompanied by tremor, anxiety, shortness of breath, cyanosis, pharyngeal spasm, fever, sweating, and a decrease in blood pressure. have a specific smell. Tolerable Upper Intake Levels for the Vitamin have not been established. The daily requirement for adults in vitamin B1 is 1.5 mg/day [1, p.113; 4].

Vitamin B2

Vitamin B2 (riboflavin) toxicity is very low due to poor oral absorption and rapid urinary excretion. Even at doses of 2-10 g/kg of body weight, vitamin B2 does not cause side effects when taken orally. When administered parenterally, riboflavin is slightly more toxic. The LD50 (semi-lethal dose) for rats treated with riboflavin i.p., s.c., and p.o. was shown to be 0.6 g/kg, 5 g/kg, and >10 g/kg, respectively.

Due to the low toxicity, the symptoms of an overdose of riboflavin are practically not described. The most likely symptoms are impaired liver and kidney function, pain in the right side, diarrhea, visual impairment. The daily requirement for the vitamin is 1-3 mg. The upper permissible exposure limits have not been established [1, p. 328].

Vitamin B3

Vitamin B3 (PP, nicotinic acid) has low toxicity. The most common side effect of taking it in high doses is flushing of the skin caused by vasodilatation of the skin vessels. This reaction is transient (30–90 min) and is accompanied by erythema, tingling, itching and fever. It occurs in approximately 70% of patients at the beginning of therapy and most often resembles the development of tolerance. The flushing reaction can be caused by both oral and topical exposure to nicotinic acid, which triggers the release of prostaglandin D2 from platelets and dendritic cells. The reaction can be minimized by using a slow-release nicotinic acid preparation or by using a cyclooxygenase inhibitor (eg, aspirin) before taking the drug. High doses of nicotinic acid have also been reported to cause itching, hives, and gastrointestinal disturbances (heartburn, nausea, vomiting, and sometimes diarrhea).

Long-term effects of high doses of nicotinic acid include insulin resistance, hyperuricemia, ulcerogenic effects on the gastric mucosa, liver damage. A few cases of transient elevations of plasma liver enzymes without associated hepatic dysfunction have also been reported. The maximum daily dose of vitamin PP for an adult is 500 mg [1, p. 348].

Vitamin B5

Vitamin B5 (pantothenic acid) toxicity is negligible. It has been estimated that animals can tolerate doses of pantothenic acid at least 100 times their daily requirement without adverse effects. In humans, high doses of vitamin B5 (10 g/day) have only caused mild gastrointestinal distress and diarrhea. An upper tolerated intake level for pantothenic acid has not been established. The recommended daily intake of pantothenic acid for adults is 5-10 mg (in some sources – up to 15) [1, p. 397].

Vitamin B6

The toxicity of vitamin B6 (pyridoxine) is relatively low, although high doses (greater than 2 g per day) have been shown to cause sensory neuropathy characterized by gait changes, fine motor impairment, and loss of proprioceptive and vibrational sensitivity (while usually , pain, temperature and tactile). In addition, at doses of 10-25 mg, pyridoxine has been shown to increase the conversion of levodopa to dopamine, which, unlike its predecessor, does not cross the blood-brain barrier. Thus, B6 should not be administered to individuals taking levodopa without concomitant administration of a decarboxylase inhibitor. Upper Tolerable Intakes of Vitamin B6 have not been established [1, p. 369; 5].

Vitamin B7

Vitamin B7 (H, biotin) toxicity is very low. Adverse reactions were not noted even when taking the vitamin in high doses (up to 200 mg orally or 20 mg intravenously). Animal studies have not shown any significant evidence of biotin toxicity, suggesting that animals, including humans, can tolerate the vitamin at doses at least an order of magnitude greater than their respective dietary requirements. The daily requirement for biotin is 50 mcg/day for adults. The maximum allowable levels of biotin intake have not been established [1, p. 383].

Vitamin B9

Folic acid (vitamin B9) has low toxicity. In general, oral intake of large amounts of folic acid does not cause significant side effects, however, there is a potential association between high doses of folate and epileptic reactions. They have been shown to occur in rats (1,000 times DV when parenterally administered), as well as in humans with epilepsy (data are mixed, but according to some, high doses of folic acid (1–10 mg) have been associated with increased frequency and seizure severity). Taking large amounts of folic acid by pregnant women increases the risk of having babies that are small for gestational age. In addition, folate overdose can also potentially exacerbate the effects of vitamin B12 deficiency [1, p. 427; 6, 7].

Figure 4. Recommended intake levels for folic acid

Vitamin B12

Vitamin B12 (cyanocobalamin) has no appreciable toxicity. The results of studies in mice show that it is harmless when administered parenterally in mega-doses. Excess of vitamin B12 by several hundred times when taken orally does not cause significant side effects. At the same time, a high level of vitamin B12 in the blood is most often associated not with hypervitaminosis, but with the presence of serious diseases. Thus, a relationship was shown between an increased concentration of vitamin B12 in the blood serum and solid neoplasms (hepatocellular carcinoma and secondary liver tumors, breast cancer, colon cancer, stomach cancer and pancreatic tumors), hemoblastoses (chronic myelomonocytic leukemia, primary hypereosinophilic syndrome, acute myeloid leukemia, etc. ), liver diseases (acute hepatitis, cirrhosis, alcoholic liver damage, etc.), kidney diseases. The norm of B12 in serum varies on average from 190 to 663 pg/ml. The daily requirement for vitamin B12 in adults is 3.0–3.4 μg [1, p. 450; 8].

Sources:

1. The Vitamins: Fundamental Aspects in Nutrition and Health 5th Edition / Gerald F. Combs Jr. (Author), James P. McClung // Academic Press; 5th edition, 2017. 628 pages.
2. Abner E.L., et al. Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci. 2011, Vol.4, No.2, pp.158-170.
3. Mühlhöfer A., ​​et al. High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers. Eur J Clinic Nutr. 2004, Vol.58, No.8, pp.1151-1158.
4. Gromova O.A. Vitamin B1. Pediatric practice, school on vitamins and microelements. March, 2005.
5. Mars H. Levodopa, carbidopa, and pyridoxine in Parkinson disease. Metabolic interactions. Arch Neurol. 1974 Vol. 30, №6, rr.444-447
6. Moore J/L. The significance of folic acid for epilepsy patients. Epilepsy Behav. 2005, Vol.7, No.2, pp.172-181.
7. Asadi-Pooya A.A. High dose folic acid supplementation in women with epilepsy: are we sure it is safe? Seizure. 2015, Vol.27, pp.51-53.
8. Podzolkov V.I., et al. Hypervitaminosis B12 is a new marker and predictor of prognostically unfavorable diseases. Therapeutic archive, 2019, Vol. 91, No. 8, pp. 160-167.

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Liposomal Vitamin C Quick Guide｜ iHerb Blog

The information in this blog has not been verified by your country’s public health authority and is not intended for diagnosis, treatment or medical advice.
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What is Liposomal Vitamin C?

Liposomal Vitamin C is an advanced form designed for better absorption and utilization in the body. Liposomes are small, spherical cells whose outer layer is made up of fatty acids known as phospholipids, derived from sunflower or soy. Liposomes also have an inner layer composed of water and water-soluble active ingredients. Water-soluble ingredients such as vitamin C are protected in the inner layer by a liposomal structure.

The main benefit of Liposomal Vitamin C is its improved absorption. The ability of intestinal cells to absorb higher doses of vitamin C has its own threshold. This is why higher doses of vitamin C can cause excessive gas and/or diarrhea. Liposomal vitamin C is significantly more bioavailable than regular vitamin C and is absorbed into the body almost twice as fast as regular vitamin C. Liposomal vitamin C is often touted as an oral alternative to intravenous (IV) vitamin C.

Health Benefits of Liposomal Vitamin C

The health benefits of Liposomal Vitamin C reflect the same properties as regular Vitamin C. The main function of Vitamin C is the production of collagen, the main protein in the human body. Because collagen is an extremely important protein for the structures that hold our body together (connective tissue, cartilage, tendons, etc.), vitamin C is vital for wound healing, healthy gums, and preventing bruising.

In addition to its role in collagen metabolism, vitamin C is also critical for the antioxidant system, immune function, the production of chemicals and hormones in the brain, and the absorption and utilization of other nutritional factors.

There have been a number of scientific studies using liposomal vitamin C. One interesting study showed that liposomal vitamin C prevents reperfusion injury, tissue damage caused by blood returning to the tissue after a period of oxygen deficiency. Reperfusion injury is seen in many cardiac and cardiovascular procedures and occurs after a heart attack or stroke. Intravenous vitamin C also prevents reperfusion injury. Vitamin C is usually given intravenously, however, because liposomal vitamin C has such a high absorption rate, it is an oral alternative.

In the study, on 4 separate occasions, 11 men and women were randomly given oral placebo or 4 g of vitamin C via oral, oral liposomal, or intravenous delivery. The data show that oral delivery of 4 g of vitamin C encapsulated in liposomes results in circulating concentrations of vitamin C that are higher than those of conventional vitamin C but lower than intravenous administration. However, protection against ischemia-reperfusion-mediated oxidative stress is similar to that provided by intravenous administration.

One of the main applications of high doses of intravenous vitamin C is to improve the quality of life of cancer patients. Since liposomal vitamin C has a higher bioavailability, it can be an excellent alternative to intravenous administration.

Another popular use for Liposomal Vitamin C is the common cold. It has been over 40 years since Linus Pauling wrote Vitamin C and the Common Cold. Dr. Pauling’s position was based on several studies that showed that vitamin C is very effective in reducing the severity of symptoms as well as the duration of the common cold. There are currently over 30 clinical trials involving 11,350 participants. These trials are designed to evaluate the effectiveness of vitamin C in preventing or treating the common cold. Although the results of individual studies can be mixed, when combining the results of higher quality studies, scientists have concluded that vitamin C can be quite useful in reducing the risk of developing a cold. This conclusion mainly applies to people who find themselves in stressful situations.

Phospholipids derived from sunflower

The best carrier for liposomal vitamin C is phosphatidylcholine (PC), a key component of lecithin. PC helps to hold liposomes together. The ideal range would be 250-500mg of FA per dose in a liposomal vitamin C formula. FC has its own set of health benefits. The most common sources of PC are soy lecithin and sunflower lecithin. Sunflower is the best choice as it removes the GMO problem and also produces a more stable liposome. If soy lecithin is used, it must be from a non-GMO source.

Quality of liposome carriers

Liposomes must be properly manufactured to achieve the desired results. The correct size should be between 100 and 400 nanometers; in addition, the quality of the liposome must be verified by an FDA regulated quality control facility.

Homemade liposomal products

There is a lot of advertising on the Internet for producing your own vitamin C. However, the process of simply mixing vitamin C powder, vodka, lecithin and water in a blender and then whisking to obtain a liposome mixture will not produce the required quality of liposomes, so they can become effective carriers for vitamin C.

Dosage

The Recommended Daily Intake (RDI) for vitamin C is 90 mg/day in adult men and 75 mg/day in adult women, with a recommended upper limit of 2000 mg/day. Liposomal vitamin C, thanks to its enhanced absorption, is suitable for daily use as well as for specific indications.