Interactions on record — worth a quick check against your medications. Based on 8 of 10 ingredients. Check your meds →
Dietary supplement

Pyruvate - F.R.I. Ingredients & Drug Interactions

by Douglas Laboratories

Capsule Category: Other Combinations
Most serious interaction: Moderate
The interaction bottom line Most serious interaction: Moderate

Pyruvate - F.R.I. is a dietary supplement by Douglas Laboratories with 10 active ingredients. Its ingredients are commonly taken for heart health, prostate health, antioxidant support.Based on those ingredients, 1,329 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Vitamin E, Hesperidin, Selenium. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Pyruvate - F.R.I. by Douglas Laboratories

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 4 of its 10 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (125 mg) without saying how much of each component you get.

Pyruvate - F.R.I. contains 10 active ingredients. The main ingredient is a pyruvate blend, a compound your body produces naturally and uses for energy.

The supplement also includes lycopene, a red pigment from tomatoes; selenium, a mineral that supports immune function and thyroid health; rutin and hesperidin, plant compounds with antioxidant properties; vitamin C, a well-known immune supporter; alpha-lipoic acid, an antioxidant; vitamin E, a fat-soluble antioxidant; and bioflavonoids and proanthocyanidins, additional plant compounds. The capsules also contain cellulose and vegetable stearate as inactive ingredients.

Does it work?

Strong evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Strong

Strong clinical evidence supports its ingredients for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Vitamin C deficiency — rated "Effective" (Vitamin C) (Natural Medicines).
  • On file: Vitamin E deficiency — rated "Effective" (Vitamin E) (Natural Medicines).
  • On file: Ataxia with vitamin E deficiency (AVED) — rated "Effective" (Vitamin E) (Natural Medicines).
  • On file: Selenium deficiency — rated "Likely Effective" (Selenium) (Natural Medicines).
  • On file: Alzheimer disease — rated "Possibly Effective" (Vitamin E) (Natural Medicines).

The evidence for this product's ingredients is mixed. Selenium has solid support for treating selenium deficiency and possibly helpful for Kashin-Beck disease, pre-eclampsia, and autoimmune thyroiditis.

Vitamin C is proven effective for vitamin C deficiency and shows promise for anemia, cataracts, and exercise-induced respiratory infections. Lycopene is possibly effective for prostate cancer but possibly ineffective for bladder cancer and diabetes.

Alpha-lipoic acid is possibly effective for diabetic nerve damage and may help with cholesterol and weight. Pyruvate is possibly effective for obesity.

Vitamin E is proven effective for vitamin E deficiency and shows promise for Alzheimer disease and several other conditions. For rutin, hesperidin, bioflavonoids, and proanthocyanidins, the evidence on file is insufficient to rate their effectiveness, or no established rating exists.

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 8 of the 8 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 8 of 8.
  • General safety write-ups exist for 8 of 8.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most of these ingredients are generally well tolerated at normal doses. Lycopene, selenium in recommended amounts, vitamin C at dietary levels, and alpha-lipoic acid are each generally well tolerated, though selenium can be toxic in excess and high-dose vitamin C can cause stomach upset and diarrhea.

Vitamin E at usual amounts is safe, but high-dose long-term use may increase bleeding risk. Pyruvate commonly causes bloating, diarrhea, and flatulence, especially at higher doses.

Rutin may cause headache, flushing, or rash in some people. Hesperidin is generally well tolerated, though a rare case of allergic skin reaction has been reported.

For pregnancy, lycopene and rutin are rated Likely Safe, but selenium is rated Possibly Safe with a caution about high-dose supplements, hesperidin is rated Possibly Safe in some sources but avoidance is advised in others, vitamin C is rated Likely Safe at normal amounts but high-dose supplements should be avoided, alpha-lipoic acid and pyruvate are rated as having insufficient data and should be avoided unless your doctor advises otherwise, and vitamin E is rated Possibly Safe. For breastfeeding, lycopene is Likely Safe; selenium is Possibly Safe with caution; hesperidin and pyruvate should be avoided due to insufficient safety data; vitamin C at recommended amounts is safe but high-dose supplements should be avoided; alpha-lipoic acid should be avoided; and vitamin E is Likely Safe at normal amounts.

We hold no safety data on file for bioflavonoids and proanthocyanidins.

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

The most serious documented interaction for these ingredients is Moderate. Check your medications for a personalized result.

Why this rating?
  • 7 of the 8 matched ingredients can interact with medications — Rutin, Lycopene, Alpha-lipoic Acid, Vitamin E, Vitamin C, among others.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications.
  • For scale: 1,330 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, double-check with your doctor or pharmacist if you take blood thinners or antiplatelet drugs — lycopene, selenium, alpha-lipoic acid, and vitamin E all carry Moderate bleeding risk with these medications. Also confirm your use if you take heart medications like verapamil or diltiazem, antidiabetes drugs, antihypertensive (blood pressure) medications, barbiturates, warfarin, immunosuppressants, or any chemotherapy agents, as well as oral contraceptives, estrogen replacement, niacin, thyroid hormone, or certain antiretroviral drugs.

No interactions are documented for bioflavonoids and proanthocyanidins.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with strong clinical evidence behind its ingredients' uses. Moderate medication interactions have been identified, and safety information is well characterized.

This product may appeal to you if you're looking to support overall antioxidant health, energy metabolism, or prostate health, and your medications don't conflict with it. However, if you take blood thinners, heart medications, antidiabetes drugs, antihypertensives, immunosuppressants, or chemotherapy, be cautious — many of this product's ingredients interact with these drug types.

Pregnant or breastfeeding individuals should talk with their doctor or pharmacist before starting, as the safety data for several ingredients are limited or advise against use in these situations. Check your specific medications against the interaction tool on this page and discuss the results with your own healthcare provider before you begin.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 8 of 10 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jun 1, 2012.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Pyruvate - F.R.I., straight from the product label.

Brand Douglas Laboratories
Barcode (UPC) 310539012468
Net contents 180 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Jun 1, 2012
DSLD ID 9851
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other
Intended target group(s) Adult (18 - 50 Years), Dairy Free, Sugar Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Pyruvate - F.R.I. by Douglas Laboratories, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Vegetarian Capsule(s)
Maximum serving Sizes:
3 Vegetarian Capsule(s)
Servings per container
30
UPC/BARCODE
310539012468
IngredientAmount% DV
Lycopene0 NP--
Proprietary Blend125 mg--
Selenium100 mcg143%
Rutin0 NP--
Hesperidin0 NP--
Vitamin C250 mg417%
Alpha-Lipoic Acid0 NP--
Bioflavonoids0 NP--
Vitamin E200 IU667%
Pyruvate Blend2000 mg--
Proanthocyanidins0 NP--

Other ingredients: Cellulose, Vegetable Stearate

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
General

Formula #80435

General Statements

(FRI = pyruvate free radical inhibitor)

FDA Statement of Identity

A Dietary Supplement

Formulation

This product contains NO yeast, wheat gluten, soy protein, milk/dairy, corn, sodium, sugar, starch, artificial coloring, preservatives or flavoring.

Suggested/Recommended/Usage/Directions

Suggested Usage: Adults take 2-3 capsules, 1-2 times daily or as directed by physician.

Precautions

KEEP OUT OF REACH OF CHILDREN.

Tamper resistant package, do not use if outer seal is missing.

Storage

For optimal storage conditions, store in a cool, dry place. (59(0)-77(0)F/15(0)-25(0)C) (35-65% relative humidity)

See for yourself

Pyruvate - F.R.I. by Douglas Laboratories label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

What’s inside

The Ingredients in Pyruvate - F.R.I. by Douglas Laboratories

These are the 10 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Vegetarian Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Proprietary Blend

125 mg per serving

Selenium

Interacts with
321 drugs
100 mcg per serving Form: Selenomethionine

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who...

Selenium monograph & interactions

Vitamin C

Interacts with
207 drugs
250 mg per serving Form: Ascorbic Acid, Ascorbyl Palmitate

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for im...

Vitamin C monograph & interactions

Vitamin E

Interacts with
764 drugs
200 IU per serving Form: D-Alpha-Tocopherol Succinate, Mixed Tocopherols

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correc...

Vitamin E monograph & interactions

Pyruvate Blend

No known
interactions
2000 mg per serving Form: Calcium, Potassium, Sodium

Pyruvate is a natural compound your body makes during the breakdown of sugar for energy, and it is sold as a supplement mainly for weight loss and ath...

Pyruvate Blend monograph & interactions

Other (inactive) ingredients: Cellulose, Vegetable Stearate. These complete the product’s ingredient list but are not active constituents.

Interaction report

Pyruvate - F.R.I. by Douglas Laboratories Drug Interactions

Want to check YOUR meds against Pyruvate - F.R.I.?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

Go to the checker
1,329Drugs
1,307 Moderate 22 Minor

Ingredients driving the most interactions

Vitamin E 764
Selenium 321
Vitamin C 207

Each ingredient & the kinds of drugs it affects

For each ingredient in Pyruvate - F.R.I. with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Vitamin E8 drug types · 764 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of alkylating agents.
There's concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding.
Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors. These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily. Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol. RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors. Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.

Likelihood Possible Evidence B
Antitumor Antibiotics

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of antitumor antibiotics.
There's concern that antioxidants could reduce the activity of antitumor antibiotic drugs such as doxorubicin, which generate free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

A specific form of vitamin E might increase absorption and levels of cyclosporine.
There is some evidence that one specific formulation of vitamin E (D-alpha-tocopheryl-polyethylene glycol-1000 succinate, TPGS, tocophersolan, Liqui-E) might increase absorption of cyclosporine. This vitamin E formulation forms micelles which seems to increase absorption of cyclosporine by 40% to 72% in some patients. However, this interaction is unlikely to occur with the usual forms of vitamin E.

Likelihood Unlikely Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.
Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.

Likelihood Possible Evidence D
Selumetinib (Koselugo)

Taking selumetinib with vitamin E can result in a total daily dose of vitamin E that exceeds safe limits and therefore might increase the risk of bleeding.
Selumetinib contains 48-54 IU vitamin E per capsule. The increased risk of bleeding with vitamin E appears to be dose-dependent. Be cautious when using selumetinib in combination with supplemental vitamin E, especially in patients at higher risk of bleed, such as those with chronic conditions and those taking antiplatelet drugs.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Using vitamin E with warfarin might increase the risk of bleeding.
Due to interference with production of vitamin K-dependent clotting factors, use of more than 400 IU of vitamin E daily with warfarin might increase prothrombin time (PT), INR, and the risk of bleeding,. At a dose of 1000 IU per day, vitamin E can antagonize vitamin K-dependent clotting factors even in people not taking warfarin. Limited clinical evidence suggests that doses up to 1200 IU daily may be used safely by patients taking warfarin, but this may not be applicable in all patient populations.

Likelihood Possible Evidence B
Niacin

Vitamin E might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises high-density lipoprotein (HDL) cholesterol levels in people with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50%. Vitamin E alone combined with a statin does not seem to decrease HDL levels. It is not known whether the adverse effect on HDL is due to one of the other antioxidants or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A

Hesperidin7 drug types · 702 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, hesperidin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Animal research suggests that hesperetin, a bioflavonoid aglycone derivative of hesperidin, may have antiplatelet activity.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension.
Some clinical and animal research shows that hesperidin can decrease blood pressure. However, other clinical research shows that hesperidin does not affect blood pressure.

Likelihood Possible Evidence D
Celiprolol (Celicard)

Theoretically, hesperidin may decrease the levels and clinical effects of celiprolol.
Animal research shows that concomitant use of hesperidin may reduce the plasma area under the curve of celiprolol by up to 75%. This effect has not been reported in humans.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, concomitant use with CNS depressants may cause additive sedative effects.
Animal studies show that hesperidin has sedative effects, due to opioid receptor activity and can increase sedation when used with diazepam. This effect has not been reported in humans.

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

Theoretically, hesperidin may increase the levels and clinical effects of diltiazem.
Animal research suggests that hesperidin may enhance the bioavailability of diltiazem, increasing the plasma area under the curve of diltiazem by up to 65.3%. This effect has not been reported in humans.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, hesperidin might inhibit P-glycoprotein-mediated drug efflux and potentially increase levels of drugs that are substrates of P-glycoprotein.
In vitro research shows that hesperidin can inhibit P-glycoprotein efflux. This effect has not been reported in humans.

Likelihood Possible Evidence D
Verapamil (Calan, Others)

Theoretically, hesperidin might increase the levels and clinical effects of verapamil.
Animal research suggests that hesperidin may enhance the bioavailability of verapamil, increasing the plasma area under the curve of verapamil by 96.8%. This effect has not been reported in humans

Likelihood Possible Evidence D

Selenium6 drug types · 321 drugs

Anticoagulant/Antiplatelet Drugs

Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity. Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation.

Likelihood Possible Evidence D
Barbiturates

Theoretically, selenium might prolong the sedating effects of barbiturates.
Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates. Selenium seems to prolong the sedative effect of pentobarbital in animal models.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, selenium might interfere with warfarin activity.
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors. Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity.

Likelihood Possible Evidence D
Contraceptive Drugs

Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels. It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium.

Likelihood Possible Evidence B
Niacin

Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A

Alpha-Lipoic Acid5 drug types · 263 drugs

Alkylating Agents

Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents.
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro, alpha-lipoic acid inhibits platelet aggregation.

Likelihood Possible Evidence D
Antitumor Antibiotics

Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.
Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.
Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels, larger clinical studies in patients with diabetes have shown no clinically meaningful effect. Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers.

Likelihood Unlikely Evidence B

Vitamin C13 drug types · 207 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Aluminum

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Likelihood Probable Evidence B
Antitumor Antibiotics

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Estrogens

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Likelihood Probable Evidence B
Fluphenazine (Prolixin)

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Likelihood Possible Evidence D
Indinavir (Crixivan)

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

Likelihood Probable Evidence B
Warfarin (Coumadin)

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Likelihood Probable Evidence B
Aspirin

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Likelihood Possible Evidence B
Choline Magnesium Trisalicylate (Trilisate)

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Niacin

Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Salsalate (Disalcid)

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B

Lycopene1 drug type · 122 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking lycopene with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
In vitro research shows that lycopene has antiplatelet effects.

Likelihood Possible Evidence D

Rutin1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking rutin with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research suggests that rutin has hypoglycemic effects.

Likelihood Possible Evidence D
The maker

Brand information

Manufacturer and brand details for Pyruvate - F.R.I., from the product label.

Douglas Laboratories

See all Douglas Laboratories products
Name
Douglas Laboratories
City
Pittsburgh
State
PA
ZipCode
15205
Web Address
www.douglaslabs.com
Pharmacist Counseling Corner

Pyruvate - F.R.I. by Douglas Laboratories: Common Questions

Does Pyruvate - F.R.I. by Douglas Laboratories interact with any medications?
Yes. Based on its ingredients, Pyruvate - F.R.I. has a known interaction with 1,329 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Pyruvate - F.R.I. contains 10 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take this if I'm on warfarin or another blood thinner?
This product carries a Moderate concern with blood thinners because selenium, lycopene, vitamin E, and alpha-lipoic acid all have antiplatelet effects. Your doctor or pharmacist needs to review the interaction tool results for your exact medications before you start.
Is pyruvate actually effective for weight loss?
Pyruvate is rated Possibly Effective for obesity based on available evidence, so there's some support but it's not proven. Your results may vary, and high doses can cause digestive upset.
What are the most common side effects?
Gastrointestinal upset is most common — lycopene, selenium, vitamin C, alpha-lipoic acid, and pyruvate can all cause diarrhea, nausea, bloating, or flatulence. Rutin may cause headache or rash in some people.
Is it safe to take during pregnancy?
The safety data differ by ingredient. Lycopene and rutin are considered Likely Safe, but selenium, hesperidin, alpha-lipoic acid, and pyruvate have insufficient data or cautions against use during pregnancy. Talk with your doctor or pharmacist for personalized advice.
Is this safe to take while breastfeeding?
Again, it depends on the ingredient. Lycopene and vitamin E are considered safe, but selenium needs caution at high doses, and hesperidin, alpha-lipoic acid, and pyruvate should be avoided because safety has not been studied. Ask your doctor or pharmacist.
Does this product have any fillers or other inactive ingredients?
Yes — it contains cellulose and vegetable stearate as inactive ingredients to hold the capsule together and maintain the formula.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Pyruvate - F.R.I. label
Go deeper

The Full Monographs Behind Pyruvate - F.R.I.’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Lycopene

Interacts with 122 drugs

Lycopene is a red plant pigment and antioxidant found mainly in tomatoes and other red fruits. Eating lycopene-rich foods is linked with possible heart and prostate benefits, but evidence fr...

Read the full Lycopene monograph →
Herb & supplement monograph

Rutin

Interacts with 86 drugs

Rutin is a plant flavonoid (often taken from buckwheat or citrus) that people use mainly for blood vessel and circulation problems like varicose veins and hemorrhoids. The evidence is limite...

Read the full Rutin monograph →
Herb & supplement monograph

Hesperidin

Interacts with 702 drugs

Hesperidin is a flavonoid found in citrus fruits that is often combined with diosmin and used for vein and circulation problems like hemorrhoids and varicose veins. Some evidence supports th...

Read the full Hesperidin monograph →
Herb & supplement monograph

Alpha-lipoic Acid

Interacts with 263 drugs

Alpha-lipoic acid (ALA) is an antioxidant made naturally by the body and found in small amounts in foods. It is most studied for diabetic nerve pain, where some evidence suggests it may help...

Read the full Alpha-lipoic Acid monograph →
Herb & supplement monograph

Selenium

Interacts with 321 drugs

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who eat a varied diet get enough, and supple...

Read the full Selenium monograph →
Herb & supplement monograph

Vitamin C

Interacts with 207 drugs

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for immune function, collagen, and acts as an...

Read the full Vitamin C monograph →
Herb & supplement monograph

Vitamin E

Interacts with 764 drugs

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correct a true deficiency, but high-dose vitam...

Read the full Vitamin E monograph →
Herb & supplement monograph

Pyruvate

Pyruvate is a natural compound your body makes during the breakdown of sugar for energy, and it is sold as a supplement mainly for weight loss and athletic performance. The evidence for thes...

Read the full Pyruvate monograph →
Sources

Sources & How We Checked

Pyruvate - F.R.I.'s label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 229 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Lycopene 10 references
  1. Sharma, J. B., Kumar, A., Kumar, A., Malhotra, M., Arora, R., Prasad, S., and Batra, S. Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas. Int J Gynaecol.Obstet. 2003;81(3):257-262. PubMed
  2. Hsiao, G., Wang, Y., Tzu, N. H., Fong, T. H., Shen, M. Y., Lin, K. H., Chou, D. S., and Sheu, J. R. Inhibitory effects of lycopene on in vitro platelet activation and in vivo prevention of thrombus formation. J Lab Clin Med 2005;146(4):216-226. PubMed
  3. Clark, P. E., Hall, M. C., Borden, L. S., Jr., Miller, A. A., Hu, J. J., Lee, W. R., Stindt, D., D'Agostino, R., Jr., Lovato, J., Harmon, M., and Torti, F. M. Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse o
  4. O'Kennedy, N., Crosbie, L., Whelan, S., Luther, V., Horgan, G., Broom, J. I., Webb, D. J., and Duttaroy, A. K. Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans. Am.J.Clin.Nutr. 2006;84(3):561-569. PubMed
  5. Jatoi, A., Burch, P., Hillman, D., Vanyo, J. M., Dakhil, S., Nikcevich, D., Rowland, K., Morton, R., Flynn, P. J., Young, C., and Tan, W. A tomato-based, lycopene-containing intervention for androgen-independent prostate cancer: results of a Phase II stu
  6. Schwenke, C., Ubrig, B., Thurmann, P., Eggersmann, C., and Roth, S. Lycopene for advanced hormone refractory prostate cancer: a prospective, open phase II pilot study. J.Urol. 2009;181(3):1098-1103. PubMed
  7. Banerjee, S., Jeyaseelan, S., and Guleria, R. Trial of lycopene to prevent pre-eclampsia in healthy primigravidas: results show some adverse effects. J.Obstet.Gynaecol.Res. 2009;35(3):477-482. PubMed
  8. Haseen, F., Cantwell, M. M., O'Sullivan, J. M., and Murray, L. J. Is there a benefit from lycopene supplementation in men with prostate cancer? A systematic review. Prostate Cancer Prostatic.Dis. 2009;12(4):325-332. PubMed
  9. Ilic, D., Forbes, K. M., and Hassed, C. Lycopene for the prevention of prostate cancer. Cochrane.Database.Syst.Rev. 2011;(11):CD008007. PubMed
  10. Sawardekar SB, Patel TC, Uchil D. Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: an in vitro study. Indian J Pharmacol 2016;48:26-31. PubMed

See these in context on the Lycopene monograph →

Selenium 36 references
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  2. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  3. Trafikowska U, Zachara BA, Wiacek M, et al. Selenium supply and glutathione peroxidase activity in breastfed Polish infants. Acta Paediatr 1996;85:1143-5. PubMed
  4. Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 2003;95:1477-81.. PubMed
  5. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  6. Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96. PubMed
  7. Davila JC, Edds GT, Osuna O, Simpson CF. Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium. Am J Vet Res 1983;44:1877-83. DOI
  8. Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988;73:163-5.
  9. Lloyd B, Lloyd RS, Clayton BE. Effect of smoking, alcohol and other factors on the selenium status of a healthy population. J Epidemiol Commun Health 1983;37:213-7. PubMed
  10. Capel ID, Jenner M, Williams DC, et al. The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity. J Steroid Biochem 1981;14:729-32. PubMed
  11. Contempre B, Dumont JE, Ngo B, et al. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol PubMed
  12. Hofbauer LC, Spitzweg C, Magerstadt RA, Heufelder AE. Selenium-induced thyroid dysfunction. Postgrad Med J 1997;73:103-4. PubMed
  13. Debski B, Milner JA. Dietary selenium supplementation prolongs pentobarbital induced hypnosis. J Nutr Biochem 2004;15:548-53. PubMed
  14. Ishikawa M, Sasaki M, Koiwai K, et al. Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. J Pharmacobiodyn 1992;15:377-85. PubMed
  15. Lippmann SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 2009;301:39-51. DOI
  16. Reid SM, Middleton P, Cossich MC, Crowther CA. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database Syst Rev 2010;(7):CD007752. PubMed
  17. Vinceti, M., Wei, E. T., Malagoli, C., Bergomi, M., and Vivoli, G. Adverse health effects of selenium in humans. Rev.Environ.Health 2001;16(4):233-251. PubMed
  18. Abrams, C. K., Siram, S. M., Galsim, C., Johnson-Hamilton, H., Munford, F. L., and Mezghebe, H. Selenium deficiency in long-term total parenteral nutrition. Nutr Clin Pract 1992;7(4):175-178. PubMed
  19. Spiller, H. A. and Pfiefer, E. Two fatal cases of selenium toxicity. Forensic Sci Int 8-24-2007;171(1):67-72. PubMed
  20. Negro, R., Greco, G., Mangieri, T., Pezzarossa, A., Dazzi, D., and Hassan, H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol.Metab 2007;92(4):1263-1268. PubMed
  21. Alexander, J. Selenium. Novartis.Found.Symp 2007;282:143-149.
  22. Salonen, J. T., Salonen, R., Seppanen, K., Rinta-Kiikka, S., Kuukka, M., Korpela, H., Alfthan, G., Kantola, M., and Schalch, W. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial
  23. Kupka, R., Mugusi, F., Aboud, S., Msamanga, G. I., Finkelstein, J. L., Spiegelman, D., and Fawzi, W. W. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and chil
  24. Kamble, P., Mohsin, N., Jha, A., Date, A., Upadhaya, A., Mohammad, E., Khalil, M., Pakkyara, A., and Budruddin, M. Selenium intoxication with selenite broth resulting in acute renal failure and severe gastritis. Saudi.J Kidney Dis.Transpl. 2009;20(1):106
  25. Peretz, A., Neve, J., Desmedt, J., Duchateau, J., Dramaix, M., and Famaey, J. P. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am.J Clin.Nutr. 1991;53(5):1323-1328. PubMed
  26. Kumpulainen, J., Salmenpera, L., Siimes, M. A., Koivistoinen, P., and Perheentupa, J. Selenium status of exclusively breast-fed infants as influenced by maternal organic or inorganic selenium supplementation. Am.J Clin.Nutr. 1985;42(5):829-835. PubMed
  27. Han, L. and Zhou, S. M. Selenium supplement in the prevention of pregnancy induced hypertension. Chin Med J (Engl) 1994;107(11):870-871.
  28. Kiremidjian-Schumacher, L., Roy, M., Wishe, H. I., Cohen, M. W., and Stotzky, G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol.Trace Elem.Res. 1994;41(1-2):115-127. PubMed
  29. Srivastava, A. K., Gupta, B. N., Bihari, V., and Gaur, J. S. Generalized hair loss and selenium exposure. Vet.Hum.Toxicol. 1995;37(5):468-469.
  30. Sudfeld CR, Aboud S, Kupka R, et al. Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women. Nutrition 2014;30(9):1081-4. PubMed
  31. Rees K, Hartley L, Day C, et al. Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1:CD009671. PubMed
  32. Thompson PA, Ashbeck EL, Roe DJ, et al. Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. J Natl Cancer Inst. 2016;108(12). PubMed
  33. Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis. Thyroid 2016;26(12):1681-92. PubMed
  34. Vinceti M, Filippini T, Rothman KJ. Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Epidemiol. 2018 Sep;33(9):789-810. Epub 2018 Jul 5. Review. PubMed
  35. Fallah S, Sani FV, Firoozrai M. Effect of contraceptive pill on the selenium and zinc status of healthy subjects. Contraception. 2009;80(1):40-3. PubMed
  36. Malpas CB, Vivash L, Genc S, et al. A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer's Disease. J Alzheimers Dis. 2016;54(1):223-232. PubMed

See these in context on the Selenium monograph →

Rutin 2 references
  1. Mehta DK (Ex Ed). British National Formulary, Number 37. British Medical Association and Royal Pharmaceutical Society of Great Britain: London, England, March 1999.
  2. Sun C, Wang L, Sun J, Wang Z, Tang Z. Hypoglycemic and hypolipidemic effects of rutin on hyperglycemic rats. J Tradit Chin Med. 2020;40(4):640-645.

See these in context on the Rutin monograph →

Hesperidin 14 references
  1. Fernandez, S. P., Wasowski, C., Paladini, A. C., and Marder, M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur.J.Pharmacol. 4-11-2005;512(2-3):189-198. PubMed
  2. Jin, Y. R., Han, X. H., Zhang, Y. H., Lee, J. J., Lim, Y., Chung, J. H., and Yun, Y. P. Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity. Atherosclerosis 200
  3. Loscalzo, L. M., Wasowski, C., Paladini, A. C., and Marder, M. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur.J.Pharmacol. 2-12-2008;580(3):306-313. PubMed
  4. Yamamoto, M., Suzuki, A., Jokura, H., Yamamoto, N., and Hase, T. Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition 2008;24(5):470-476. PubMed
  5. El-Readi, M. Z., Hamdan, D., Farrag, N., El-Shazly, A., and Wink, M. Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines. Eur.J.Pharmacol. 1-25-2010;626(2-3):139-145 PubMed
  6. Buckshee, K., Takkar, D., and Aggarwal, N. Micronized flavonoid therapy in internal hemorrhoids of pregnancy. Int J Gynaecol Obstet 1997;57(2):145-151. PubMed
  7. Uesawa, Y. and Mohri, K. Hesperidin in orange juice reduces the absorption of celiprolol in rats. Biopharm Drug Dispos. 2008;29(3):185-188. PubMed
  8. Cho, YA, Choi, DH, and Choi, JS. Effect of hesperidin on the oral pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. J Pharm Pharmacol. 2009;61(6):825-829. PubMed
  9. Piao, YJ and Choi, JS. Enhanced bioavailability of verapamil after oral administration with hesperidin in rats. Arch Pharm Res. 2008;31(4):518-522. PubMed
  10. Andersen KE. Hesperidin methyl chalcone?-?a new cosmetic contact allergen. Contact Dermatitis. 2015;72(6):402-4. PubMed
  11. Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. Am J Clin Nutr 2011;93(1):73-80. PubMed
  12. Homayouni F, Haidari F, Hedayati M, Zakerkish M, Ahmadi K. Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial. Phytother Res. 2018;32(6):1073-1079. PubMed
  13. Mohammadi M, Ramezani-Jolfaie N, Lorzadeh E, Khoshbakht Y, Salehi-Abargouei A. Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled clinical trials PubMed
  14. Valls RM, Pedret A, Calderón-Pérez L, et al. Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study). Eur J Nutr. 2021;60(3):1277-1288. PubMed

See these in context on the Hesperidin monograph →

Vitamin C 51 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
  6. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. PubMed
  7. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  8. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  9. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  10. Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21. PubMed
  11. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  12. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671. DOI
  13. Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479. DOI
  14. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166. DOI
  15. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;170:397-401.. PubMed
  16. Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.
  17. Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601. PubMed
  18. Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7. PubMed
  19. Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413. DOI
  20. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31. PubMed
  21. Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008. DOI
  22. Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
  23. Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70. PubMed
  24. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7. PubMed
  26. Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6. PubMed
  27. Lee DH, Folsom AR, Harnack L, et al. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr 2004;80:1194-200. PubMed
  28. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225-32. PubMed
  29. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  30. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  31. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  32. Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.
  33. Gruenwald, J., Graubaum, H. J., Busch, R., and Bentley, C. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv.Ther. 2006;23(1):171-178.
  34. Rahimi, R., Nikfar, S., Rezaie, A., and Abdollahi, M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens.Pregnancy. 2009;28(4):417-434. PubMed
  35. Einerson, B., Nathorn, C., Kitiyakara, C., Sirada, M., and Thamlikitkul, V. The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis patients receiving erythropoietin: a meta-analysis. J Med.Assoc.Thai. 2011;94 Suppl 1:S134-S146.
  36. Li, G., Li, L., Yu, C., and Chen, L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis. Br.J Nutr 2011;106(11):1632-1637.
  37. Chen X, Shen L, Gu X, et al. High-dose supplementation with vitamin C--induced pediatric urolithiasis: the first case report in a child and literature review. Urology. 2014;84(4):922-4. PubMed
  38. Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6. PubMed
  39. Yaich S, Chaabouni Y, Charfeddine K, et al. Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(1):113-6. PubMed
  40. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  41. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PubMed
  42. Seo MS, Kim JK, Shim JY. High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma. Yonsei Med J. 2015;56(5):1449-52. PubMed
  43. Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403. PubMed
  44. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic acid supplements and kidney stones incidence among men and women: a systematic review and meta-analysis. Urol J. 2019;16(2):115-120.
  45. Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2 PubMed
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Alpha-lipoic Acid 48 references
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Pyruvate 4 references
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