Some studies have found that taking vitamin C supplements can reduce the duration and severity of colds, particularly in individuals with low vitamin C levels or under high physical stress. However, results are mixed, and more research is needed to establish the effectiveness of vitamin C for this purpose.

Vitamin C is a potent antioxidant that can help protect cells from oxidative damage caused by free radicals. This can potentially reduce the risk of chronic diseases such as cancer, heart disease, and Alzheimer's.

Vitamin C can enhance the absorption of iron from plant-based foods by reducing it to a more absorbable form. This can potentially help prevent iron deficiency anemia.

Some studies have suggested that vitamin C intake may reduce the risk of cataracts, a condition characterized by clouding of the eye's lens that can lead to vision loss.

Vitamin K plays a key role in maintaining bone health. It is involved in the modification of osteocalcin, a protein that strengthens the composition of bones.

Vitamin K is believed to help prevent the hardening of arteries, which can reduce the risk of heart disease.

Phytosterols in the diet could help lower cholesterol levels.

Allicin is recognized for its potential effects on heart health, particularly for improving cholesterol levels, reducing blood pressure, and slowing the progression of atherosclerosis.

Allicin has been linked with antiviral, and antibacterial effects

Garlic contains antioxidants that support the body's protective mechanisms against oxidative damage. This may have benefits for long-term health, including reduced risk of Alzheimer's.

Garlic has been found to boost the function of the immune system. Some studies have shown that regular consumption of garlic extract can reduce the risk of getting a cold or flu.

In particular, lowering the risk of cancer.

Studies have shown that quercetin can inhibit inflammation and reduce oxidative stress, which can contribute to chronic diseases such as heart disease, diabetes, and cancer.

Research has suggested that quercetin may have cardioprotective effects, such as reducing blood pressure, inhibiting platelet aggregation, and improving endothelial function. However, more research is needed to confirm these findings.

Some studies have found that quercetin supplementation may improve endurance exercise performance and reduce fatigue. However, results are mixed, and more research is needed to establish the effectiveness of quercetin for this purpose.

Studies have shown that quercetin can induce apoptosis (programmed cell death) in cancer cells and inhibit the growth and spread of tumors in animal studies. However, more research is needed to determine its effectiveness in humans.

Some studies have suggested that quercetin may have neuroprotective effects and improve cognitive function in animal models and human trials.

Quercetin could have the ability to counteract PCOS complications.

Onion consumption has been shown to have cardioprotective effects

Lycopene has antioxidant properties that help neutralize free radicals and prevent cellular damage, lowering the risk of cancer.

Lycopene aids in reducing inflammation and oxidative stress, leading to better overall cardiovascular health.

Some studies have found that lycopene supplementation can reduce markers of inflammation in the body, which may help protect against chronic diseases like heart disease and cancer.

Lycopene may help protect against UV damage and improve skin texture and hydration, although more research is needed to establish its effectiveness.

Studies have found that lycopene supplementation may improve sperm quality and reduce oxidative stress in men with fertility problems. However, more research is needed to confirm these findings.

Cabbage Rolls

Water

Energy

Energy (by joule)

Protein

Total lipid (fat)

Carbohydrate, by difference

Fiber, total dietary

Sugars, total including NLEA

Sucrose

Glucose

Fructose

Maltose

Calcium, Ca

Iron, Fe

Magnesium, Mg

Phosphorus, P

Potassium, K

Sodium, Na

Zinc, Zn

Copper, Cu

Manganese, Mn

Selenium, Se

Fluoride, F

Vitamin C, total ascorbic acid

Thiamin

Riboflavin

Niacin

Pantothenic acid

Vitamin B-6

Folate, total

Folate, food

Folate, DFE

Choline, total

Betaine

Vitamin A, RAE

Carotene, beta

Carotene, alpha

Vitamin A, IU

Lutein + zeaxanthin

Vitamin E (alpha-tocopherol)

Tocotrienol, alpha

Vitamin K (phylloquinone)

Fatty acids, total saturated

SFA 16:0

Fatty acids, total monounsaturated

MUFA 18:1

Fatty acids, total polyunsaturated

PUFA 18:2

Phytosterols

Tryptophan

Threonine

Isoleucine

Leucine

Lysine

Methionine

Cystine

Phenylalanine

Tyrosine

Valine

Arginine

Histidine

Alanine

Aspartic acid

Glutamic acid

Glycine

Proline

Serine

SFA 10:0

PUFA 18:3

Allicin

Total dietary fiber (AOAC 2011.25)

Quercetin

Taxifolin

Organosulfurs

SFA 14:0

SFA 18:0

MUFA 16:1

Cryptoxanthin, beta

Lycopene

Tocopherol, beta

Tocopherol, gamma

Cabbage

Garlic

Onion

Rice

Tomato Sauce

The severe, acute respiratory syndrome COVID-19 that was first reported in China in December 2019 quickly became a global pandemic that has resulted in over 100 million infections and more than 2 million deaths.

COVID-19 Knowledge, Attitudes, and Preventive Measures of University Students in Bahrain.

Sodium iron ethylenediaminetetracetic acid (NaFeEDTA) has been recommended for food fortification programmes to improve iron status but its performance in commercial products has not been evaluated. The effect of EDTA on iron absorption from fortified cornflakes, given as part of a typical Western breakfast, was determined in a double-blind randomised study with 20 non-anaemic female volunteers, using experimentally prepared iron compounds, enriched with 58Fe, and faecal monitoring. Five meals were compared: hydrogen reduced iron, hydrogen reduced iron plus Na2EDTA (molar ratio EDTA:Fe 1:2), hydrogen reduced iron plus NaFe(III)EDTA at two different molar ratios (EDTA:total Fe 1:3 and 1:2), and hydrogen reduced iron plus 15 mg ascorbic acid (ascorbic acid:Fe 1.3:1). The iron and EDTA compounds were accurately weighed into gelatine capsules and taken with unfortified cornflakes, semi-skimmed milk and tea on two consecutive days; the iron dose per meal was 3.75 mg. Iron absorption from all five test meals was measured in each volunteer with a minimum wash-out period of 2 weeks between tests. Geometric mean iron absorption (%) from the 5 tests was 14.1, 17.6, 20.6, 24.4 and 17.5 respectively (equivalent to 0.5-0.9 mg absorbed iron). There was a significantly higher iron absorption from the mixture of reduced iron and NaFe(III)EDTA (EDTA:Fe 1:2) than from reduced iron alone (p = 0.014). It is not known whether the higher absorption was from reduced iron or NaFeEDTA or both. Absorption was not increased significantly with NaFe(III)EDTA (EDTA:Fe 1:3), Na2EDTA (EDTA:Fe 1:2) or ascorbic acid (15 mg).

Iron absorption from a breakfast cereal: effects of EDTA compounds and ascorbic acid.

Hypovitaminosis C is frequent in populations at risk (men who live alone, old people, homelessness, patients with psychiatric diseases, foodfaddists,...) and is underestimated in the general population.

[Vitamin C deficiency].

A large scale double-blind trial was conducted to test the claim that the intake of one gram of vitamin C per day substantially reduces the frequency and duration of "colds". It was found that in terms of the average number of colds and days of sickness per subject the vitamin group experienced less illness than the placebo group, but the differences were smaller than have been claimed and were statistically not significant. However, there was a statistically significant difference (P <0.05) between the two groups in the number of subjects who remained free of illness throughout the study period. Furthermore the subjects receiving the vitamin experienced approximately 30% fewer total days of disability (confined to the house or off work) than those receiving the placebo, and this difference was statistically highly significant (P <0.001). The reduction in disability appeared to be due to a lower incidence of constitutional symptoms such as chills and severe malaise, and was seen in all types of acute illness, including those which did not involve the upper respiratory tract.

Vitamin C and the common cold: a double-blind trial.

The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock.

Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial.

Oxidative stress has been implicated in cataractogenesis. Long-term intake of antioxidants may offer protection against cataract.

Antioxidant nutrient intake and the long-term incidence of age-related cataract: the Blue Mountains Eye Study.

Yellow-fleshed potatoes biofortified with iron have been developed through conventional breeding, but the bioavailability of iron is unknown.

Total Iron Absorbed from Iron-Biofortified Potatoes Is Higher than that from Nonbiofortified Potatoes: A Randomized Trial Using Stable Iron Isotopes in Women from the Peruvian Highlands.

Melasma is a very common skin problem that is much more prevalent in women. In our society, it results in many psycho-social implications and eventually leads to an impaired quality of life. Many treatment modalities have been developed for it. However, in recent years resistant forms of melasma have emerged that are unresponsive to the usual first line treatment options. Thus, this study is being conducted to explore new treatment modalities for this disease by using micro-needling with vitamin C and tranexamic acid.

Split-Face Comparative Analysis Of Micro-Needling With Tranexamic Acid Vs Vitamin C Serum In Melasma.

Airway infection leads to progressive damage of the lungs in cystic fibrosis and oxidative stress has been implicated in the etiology. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ß-carotene and selenium) or glutathione may therefore potentially help maintain an oxidant-antioxidant balance. Current literature suggests a relationship between oxidative status and lung function.

Antioxidant supplementation for lung disease in cystic fibrosis.

The aim of this study was to determine the effect of cultivars on the concentration of antioxidant compounds: total carotenoid content (TC) and vitamin C (VC), and their correlation with the total antioxidant activity (TAA) in 65 potato cultivars (Solanum tuberosum) from 10 countries. The TC content revealed a highly significant effect of the year (Y), cultivar (C) and flesh colour (FC). The TC ranged from 101.5 µg 100 g-1 DM (in cv. Kelly) to 715 µg 100 g-1 DM (in cv. Mayan Gold). The TC values were weakly correlated with years and higher in yellow-fleshed potatoes than in white-fleshed potatoes (319.9 vs. 175.6 µg 100 g-1 DM, respectively). The VC content ranged from 1.0 mg 100 g-1 FM (in cv. Bzura) to 14.8 mg 100 g-1 FM (in cv. Twinner). The content of VC were higher in yellow-fleshed (6.5 mg 100 g-1 FM) than in white-fleshed potatoes (5.8 mg 100 g-1 FM). The highest TAA were observed in cvs. Colleen, Basa, Triplo, Gatsby, Ditta, Twinner, Riviera, Michalina, Damaris, Belmonda, Ambo, Savinja, 12-LHI-6. For these cultivars, the FRAP values were 0.53 µmol TE 100 mg-1 DM and DPPH 0.55 µmol TE 100 mg-1 DM. The lowest TAA were observed in cvs.: Owacja, Mayan Gold, Kokra, Magnolia and Kelly. For them, the FRAP and DPPH values were slightly above 0.2 µmol TE 100 mg-1 DM. It was shown that the concentration of TC in potato tubers has an impact on TAA.

The Content of Total Carotenoids, Vitamin C and Antioxidant Properties of 65 Potato Cultivars Characterised under the European Project ECOBREED.

Many cancer patients on intensive chemotherapy lack vitamin C. Vitamin C stimulates the production and activation of immune cells, so perhaps supplementation could be used to improve the immunity in those patients. This review assesses the effectiveness and safety of vitamin C administration in cancer. The PubMed and EMBASE databases were searched and all study designs except for phase I studies, and case reports were included in this review. A total of 19 trials were included. In only 4 trials randomization was used to determine if patients received vitamin C or a placebo. The result of this review does not prove that there is a clinically relevant positive effect of vitamin C supplementation in cancer patients in general on the overall survival, clinical status, quality of life (QOL) and performance status (PS), since the quality of the studies published is low. Interventions and patient groups are very diverse, hence an effect in some patient groups is possible. There seems to be a better effect with intravenous than oral administration. Nevertheless, treatment with vitamin C is safe with minimal side effects. Thereby, we think it is safe to examine the effects of vitamin C on specific groups of patients in a randomized controlled setting.

The Effect of Vitamin C (Ascorbic Acid) in the Treatment of Patients with Cancer: A Systematic Review.

Oxidative stress induced by the production of reactive oxygen species may play a critical role in the stimulation of HIV replication and the development of immunodeficiency. This study was conducted as there are limited and inconclusive studies on the significance of a novel early marker of oxidative stress which can reflect the total antioxidant capacity in HIV patients,

Total antioxidant capacity--a novel early bio-chemical marker of oxidative stress in HIV infected individuals.

Randomized trials have shown that vitamin C shortens the duration of common colds. Some trials reported greater effects on severe cold symptoms compared with mild symptoms. This review systematically compares the effects of vitamin C on severe and mild common cold symptoms.

Vitamin C reduces the severity of common colds: a meta-analysis.

Many studies have shown that bioactive compounds, for example, polyphenols, and so on can play an important role in reducing oxidative stress and protect against various diseases. The sources of these compounds in the human diet include mainly fruit and good quality fruit juices, which may contain polyphenols but also other phytochemicals such as vitamin C. The purpose of the study was to analyze the antioxidant properties of vitamin C-rich juices, which underwent mild processing. The content of total polyphenols (TP, FBBB), total flavonoids (TF), total anthocyanins (TA), and vitamin C as well as the antioxidant capacity (DPPH, ABTS) were evaluated in commercial fruit juices rich in vitamin C (acerola, gojiberry, sea buckthorn, wild rose, cranberry, Japanese quince). Moreover, phenolic acids and selected flavonoids were determined by HPLC methods. Among the examined fruit juices, acerola and wild rose juices contained the highest amounts of vitamin C and total polyphenols, and had the highest antioxidant capacity. Acerola owes its high antioxidant properties mainly to vitamin C, whereas the antioxidant capacity of wild rose is also attributed to its rich content of flavonoids and phenolic acids. Sea buckthorn juice and Japanese quince juice had a lower antioxidant capacity, yet higher than determined for gojiberry and cranberry juices. Total anthocyanins were the highest in cranberry juice. The results showed that the analyzed juices were a valuable source of natural antioxidants. Generally, vitamin C-rich juices are also good source of polyphenols. Vitamin C and polyphenols act synergistically and define the antioxidant properties of juices.

Antioxidant Properties and Phenolic Compounds of Vitamin C-Rich Juices.

Background There is renewed interest in high-dose vitamin C interventions in clinical medicine due to its antioxidant properties, safe use and cost-effectiveness. Yet, randomised control trials (RCTs) employing these interventions are failing to include robust analytical methodology and proper sample handling and processing techniques. Consequently, comparisons between studies becomes impossible as there is no metrological traceability and results may be prone to pre-analytical errors. Content Through published vitamin C stability studies, method comparison papers and data from vitamin C external quality assurance programs, an assessment was made on the functionality of current methods for critically ill patient samples. Summary Data was obtained from two external quality assurance programs, two papers assessing sample stability and interlaboratory agreement and a publication on vitamin C method comparisons. A shift from spectrophotometric and enzymatic methodologies to high performance liquid chromatography (HPLC) greatly improved the variability and interlaboratory agreement. Therefore, the current analytical performance of vitamin C HPLC methodologies are acceptable for the requirements of a high-dose vitamin C RCTs. Outlook Recommendations across the total testing process of vitamin C have been provided to improve the quality of the results. The harmonisation of sample handling and processing procedures will further improve the reliability of current analytical methodologies.

Vitamin C measurement in critical illness: challenges, methodologies and quality improvements.

The role of vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for 60 years, but is widely sold and used as both a preventive and therapeutic agent.

Vitamin C for preventing and treating the common cold.

Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine.

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.

Food-to-food fortification (FtFF) with moringa leaf (iron source) and/or baobab fruit (citric acid and ascorbic acid source) (each 13-15 g/100 g porridge dry basis (db)) was studied to improve iron and zinc nutritive quality in African-type wholegrain maize-based porridges using in vitro dialysability assay. Moringa FtFF decreased percentage and total bioaccessible iron and zinc, by up to 84% and 45%, respectively. Moringa was very high in calcium, approximately 3% db and calcium-iron-phytate complexes inhibit iron bioavailability. Baobab FtFF increased percentage and total bioaccessible iron and zinc, especially in porridges containing carrot + mango (β-carotene source) and conventionally fortified with FeSO4, by up to 111% and 60%, respectively. The effects were similar to those when ascorbic and citric acids were added as mineral absorption enhancers. While moringa FtFF could be inhibitory to iron and zinc bioavailability in cereal-based porridges, baobab fruit FtFF could improve their bioavailability, especially in combination with conventional iron fortification.

Potential of moringa leaf and baobab fruit food-to-food fortification of wholegrain maize porridge to improve iron and zinc bioaccessibility.

The effect of ascorbic acid on iron retention from a diet with predicted low iron bioavailability (containing minimal meat and ascorbic acid) was investigated in iron-depleted premenopausal women. Eleven women were depleted of storage iron (indicated by serum ferritin) through a combination of diet (5.0 mg Fe/2000 kcal for 67-88 d) and phlebotomy. They then consumed a diet containing 13.7 mg Fe/2000 kcal, supplemented with placebo or ascorbic acid three times daily (1500 mg total) with meals for 5.5 wk. Ascorbic acid improved apparent iron absorption (balance method) [38 +/- 2% (means +/- SEM) vs 27 +/- 2%]. Ascorbic acid also improved hemoglobin, erythrocyte protoporphyrins, and serum iron but not hematocrit, serum ferritin, iron-binding capacity, or transferrin saturation. In iron-depleted women consuming a diet with predicted poor iron availability, ascorbic acid supplementation enhanced body iron retention for 5.5 wk.

Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women.

Vitamin C is a micronutrient present in high concentrations in normal skin and a highly prescribed cosmeceutical, well known for protecting against ultraviolet-induced pigmentation and regulating collagen production. However, there is a lack of studies evaluating the efficacy of topical vitamin C in photoaging and melasma, with this systematic review being the first to assess the existing evidence.

Efficacy of topical vitamin C in melasma and photoaging: A systematic review.

Commercialization of cactus pears based on their antioxidant properties can generate competitive advantages, and these can turn into business opportunities and the development of new products and a high-value ingredient for the food industry. This work evaluated the antioxidant activities (1,1-diphenyl-2-picrylhydrazyl radical-scavenging, protection against oxidation of a β-carotene-linoleic acid emulsion, and iron (II) chelation), the content of total phenolic compounds, ascorbic acid, betacyanin, betaxanthin and the stability of betacyanin pigments in presence of Cu (II)-dependent hydroxyl radicals (OH•), in 18 cultivars of purple, red, yellow and white cactus pear from six Mexican states. Our results indicated that the antiradical activities from yellow and white cactus pear cultivars were not significantly different (p < 0.05) and were lower than the average antiradical activities in red and purple cultivars. The red cactus pear from the state of Zacatecas showed the highest antioxidant activity. The free radical scavenging activity for red cactus pears was significantly correlated (p < 0.05) to the concentration of total phenolic compounds (R(2) = 0.90) and ascorbic acid (R(2) = 0.86). All 18 cultivars of cactus pears studied showed significant chelating activity of ferrous ions. The red and purple cactus pears showed a great stability when exposed to OH•.

Betalain, Acid ascorbic, phenolic contents and antioxidant properties of purple, red, yellow and white cactus pears.

Lens opacification or cataract reduces vision in over 80 million people worldwide and blinds 18 million. These numbers will increase dramatically as both the size of the elderly demographic and the number of those with carbohydrate metabolism-related problems increase. Preventative measures for cataract are critical because the availability of cataract surgery in much of the world is insufficient. Epidemiologic literature suggests that the risk of cataract can be diminished by diets that are optimized for vitamin C, lutein/zeaxanthin, B vitamins, omega-3 fatty acids, multivitamins, and carbohydrates: recommended levels of micronutrients are salutary. The limited data from intervention trials provide some support for observational studies with regard to nuclear - but not other types of - cataracts. Presented here are the beneficial levels of nutrients in diets or blood and the total number of participants surveyed in epidemiologic studies since a previous review in 2007.

Nutritional modulation of cataract.

Iron requirements during the weaning period are the highest per unit body weight during human life, and diet is often insufficient to cover iron needs. For the first time in infant nutrition the absorption of both nonheme and heme iron from a typical weaning gruel after addition of meat with and without ascorbic acid (AA) to improve bioavailability was studied.

The role of meat to improve the critical iron balance during weaning.

The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment.

To investigate the clinical efficacy of vitamin C-containing therapy for patients with sepsis.

The impact of vitamin C-containing treatment on the mortality of patients with sepsis: A systematic review and meta-analysis of randomized controlled trials.

Intravenous vitamin C (IVC) is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings. We conducted a systematic review of human interventional and observational studies assessing IVC for use in cancer patients.

Intravenous Vitamin C and Cancer: A Systematic Review.

The objective of the study was to develop a new method for the determination of the total content of vitamin C and dehydroascorbic acid in food, based on the technique of differential pulse voltammetry with the use of a boron-doped diamond electrode modified with mercury film. A comparison was made between the results obtained with the developed method and a proposed reference method based on high-performance liquid chromatography with spectrophotometric detection. The reduction of dehydroascorbic acid was performed with the use of tris(2-carboxyethyl)phosphine. The interference caused by the presence of tris(2-carboxyethyl)phosphine during the voltammetric determination of ascorbic acid was effectively eliminated through a reaction with N-ethylmaleimide. The conducted validation of the voltammetric method indicated that correct results of analysis of the total content of vitamin C and ascorbic acid were obtained. Analysis of the content of dehydroascorbic acid was imprecise due to the application of the differential method. The results of the analyses and the determined validation parameters of the developed method are characterised by a high degree of conformance with the results obtained with the chromatographic reference method, which indicates the equivalence of the two methods.

A New Method for the Determination of Total Content of Vitamin C, Ascorbic and Dehydroascorbic Acid, in Food Products with the Voltammetric Technique with the Use of Tris(2-carboxyethyl)phosphine as a Reducing Reagent.

Vitamin C (ascorbic acid) for preventing and treating the common cold has been a subject of controversy for 70 years.

Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease-mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.

Role of Vitamin K in Chronic Kidney Disease: A Focus on Bone and Cardiovascular Health.

Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.

Vitamin K: A novel cancer chemosensitizer.

It has been hypothesized that insufficient intake of vitamin K may increase soft-tissue calcification owing to impaired gamma-carboxylation of the vitamin K-dependent protein matrix gamma-carboxyglutamic acid. The evidence to support this putative role of vitamin K intake in atherosclerosis is reviewed.

Vitamin K intake and atherosclerosis.

Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. This review is the first to highlight differences between isoforms vitamin K1 and K2 by means of source, function, and extrahepatic activity.

Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease.

Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinone (K1). Menaquinone-4 (MK-4) is the form of vitamin K that is preferentially found in extra-hepatic tissues.

Vitamin K Metabolism in a Rat Model of Chronic Kidney Disease.

Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However, it is also involved in the maturation of another 11 or 12 proteins that play different roles, encompassing in particular the modulation of the calcification of connective tissues. Since this process is physiologically needed in bones, but is pathological in arteries, a great deal of research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases. Unfortunately, the current knowledge does not allow us to make a decisive conclusion about such a link. One possible explanation for this is the diversity of the biological activity of vitamin K, which is not a single compound but a general term covering natural plant and animal forms of vitamin K (K1 and K2) as well as their synthetic congeners (K3 and K4). Vitamin K1 (phylloquinone) is found in several vegetables. Menaquinones (MK4-MK13, a series of compounds known as vitamin K2) are mostly of a bacterial origin and are introduced into the human diet mainly through fermented cheeses. Current knowledge about the kinetics of different forms of vitamin K, their detection, and their toxicity are discussed in this review.

Vitamin K - sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity.

Background Dietary vitamin K (K1 and K2) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food-frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K1 and vitamin K2 were estimated from the food-frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52-60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17-22) years of follow-up. Compared with participants with the lowest vitamin K1 intakes, participants with the highest intakes had a 21% lower risk of an ASCVD-related hospitalization (hazard ratio, 0.79; 95% CI: 0.74-0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K2, the risk of an ASCVD-related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K2 intake (hazard ratio, 0.86; 95% CI, 0.81-0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K1 or K2. The similar inverse associations with both vitamin K1 and K2, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study.

Further research on vitamin K is necessary as growing evidence of vitamin K's importance in human health beyond blood coagulation and bone health is emerging. We present a cost-effective LC-ESI-MS/MS method for quantification of phylloquinone (PK), and menaquinones (MK) 4-10 in food using deuterium labelled (d7) compounds (d7-PK, d7-MK-4, d7-MK-7 and d7-MK-9) as internal standards. The validation of the method included assessment of matrix effect, limit of quantification (LOQ), precision, and trueness. The LC-ESI-MS/MS method runtime is 9 min. The method was compared to a validated LC-FLD method (CEN 14148), for quantification of vitamin K in broccoli, cheese, natto, liver, and microalgae. LOQs of the LC-ESI-MS/MS method were ≤4 µg/100 g food. The intra- and inter-assay precision was <15% for PK, MK-4, MK-7 and MK-9; <20% for MK-5, MK-8, and MK-10, and ≤25% for MK-6. No significant differences between the quantified content by the LC-ESI-MS/MS and LC-FLD methods were observed.

Vitamin K (phylloquinone and menaquinones) in foods - Cost-effective quantification by LC-ESI-MS/MS.

Multiple observational studies and small-scale intervention studies suggest that high vitamin K intake is associated with improved markers for cardiovascular health. Circulating phylloquinone solely represents phylloquinone (vitamin K1) intake, while dephosphorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) represents both phylloquinone and menaquinone (vitamin K2) intake. This study aims to investigate the causal relationship between genetically predicted vitamin K concentrations and the risk of CHD via a two-sample Mendelian Randomization approach.

Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study.

Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR.

Safety of Vitamin K in mechanical heart valve patients with supratherapeutic INR: A systematic review and meta-analysis.

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.

Vitamin K and Kidney Transplantation.

Vitamin K (VK), a fat-soluble vitamin, is essential for the clotting of blood because of its role in the production of clotting factors in the liver. Moreover, researchers continue to explore the role of VK as an emerging novel bioactive molecule with the potential function of improving bone health. This review focuses on the effects of VK on bone health and related mechanisms, covering VK research history, homologous analogs, dietary sources, bioavailability, recommended intake, and deficiency. The information summarized here could contribute to the basic and clinical research on VK as a natural dietary additive and drug candidate for bone health. Future research is needed to extend the dietary VK database and explore the pharmacological safety of VK and factors affecting VK bioavailability to provide more support for the bone health benefits of VK through more clinical trials.

The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism-A Review.

Vitamin K occurs in dietary supply in two major forms: phylloquinone (vitamin K1) and menaquinones (collectively referred as vitamin K2). Phylloquinone is derived from plants. There are at least 10 forms of menaquinones varying in chain length and they are produced by bacteria except menaquinone-4. Menaquinone-4 is formed from phylloquinone or other menaquinone forms. Phylloquinone is considered to be the major contributor and menaquinones are thought to contribute less to vitamin K intake in Western diets. However, less is known about the content of menaquinones than phylloquinones in foods. Vitamin K is known to function as an enzymatic cofactor in the gamma-carboxylation of vitamin K dependent proteins (VKDPs). Hepatic VKDPs are involved in coagulation. Extrahepatic VKDPs have a role e.g. in bone health and vascular calcification. However, the amount of vitamin K needed for optimal functioning of the different VKDPs is not known.

Vitamin K - a scoping review for Nordic Nutrition Recommendations 2023.

Vitamin K and its essential role in coagulation (vitamin K [Koagulation]) have been well established and accepted the world over. Many countries have a Recommended Daily Intake (RDI) for vitamin K based on early research, and its necessary role in the activation of vitamin K-dependent coagulation proteins is known. In the past few decades, the role of vitamin K-dependent proteins in processes beyond coagulation has been discovered. Various isoforms of vitamin K have been identified, and vitamin K2 specifically has been highlighted for its long half-life and extrahepatic activity, whereas the dietary form vitamin K1 has a shorter half-life. In this review, we highlight the specific activity of vitamin K2 based upon proposed frameworks necessary for a bioactive substance to be recommended for an RDI. Vitamin K2 meets all these criteria and should be considered for a specific dietary recommendation intake.

Vitamin K2 Needs an RDI Separate from Vitamin K1.

To assess growing evidence that vitamin K (phylloquinone) plays an important role in bone health and, subsequently, in prevention of osteoporotic fractures.

Bone health. New role for vitamin K?

Nuts (tree nuts and peanuts) are nutrient dense foods with complex matrices rich in unsaturated fatty and other bioactive compounds: high-quality vegetable protein, fiber, minerals, tocopherols, phytosterols, and phenolic compounds. By virtue of their unique composition, nuts are likely to beneficially impact health outcomes. Epidemiologic studies have associated nut consumption with a reduced incidence of coronary heart disease and gallstones in both genders and diabetes in women. Limited evidence also suggests beneficial effects on hypertension, cancer, and inflammation. Interventional studies consistently show that nut intake has a cholesterol-lowering effect, even in the context of healthy diets, and there is emerging evidence of beneficial effects on oxidative stress, inflammation, and vascular reactivity. Blood pressure, visceral adiposity and the metabolic syndrome also appear to be positively influenced by nut consumption. Thus it is clear that nuts have a beneficial impact on many cardiovascular risk factors. Contrary to expectations, epidemiologic studies and clinical trials suggest that regular nut consumption is unlikely to contribute to obesity and may even help in weight loss. Safety concerns are limited to the infrequent occurrence of nut allergy in children. In conclusion, nuts are nutrient rich foods with wide-ranging cardiovascular and metabolic benefits, which can be readily incorporated into healthy diets.

Health benefits of nut consumption.

Milk and dairy products contain multiple nutrients and contribute significantly to meet the nutritional requirements for protein, calcium, magnesium, phosphorus, potassium, zinc, selenium, vitamin A, riboflavin, vitamin B-12, and pantothenic acid. However, consumption of dairy is decreasing and moving away from the advised level in many countries and the potential benefits of milk and dairy products for health have come under question. This, in spite that numerous studies report health benefits associated with dairy consumption. The present supplement aims to assess and summarize scientific evidence regarding the impact of dairy intake on health and all-cause mortality, and on the prevention of diverse chronic diseases, mainly from meta-analyses of observational studies and randomized controlled trials (RCTs). There seem to positive associations between moderate maternal milk intake during pregnancy and infant birth weight, length and bone mineral content during childhood. Moreover, consumption of dairy products in older subjects may reduce the risk of frailty and decrease the risk for sarcopenia. The highest consumption of dairy products did not show a clear association with total osteoporotic fracture and hip fracture risk; however, a diminished risk of vertebral fracture was found. Analysis of the differences between high and low dairy consumption and for dose-response found no association between dairy product consumption and risk of all-cause mortality. Total and low-fat dairy consumption is associated with a reduced risk of developing metabolic syndrome and current evidence supports that consumption of dairy does not adversely affect the risk of cardiovascular outcomes and may even have a subtle protective effect. Moreover, evidence has been provided of an inverse association between the consumption of dairy products and ischemic heart disease and myocardial infarction. Also, the evidence suggests that dairy consumption, particularly low-fat dairy and yogurt is associated with a lower risk of type 2 diabetes. Likewise, moderate compared with medium consumption of dairy is associated lower risk for colorectal and bladder cancer and has no association with prostate cancer. Finally, consumption of milk or dairy products did not show a proinflammatory effect on healthy subjects, overweight/obese individuals, or individuals with other metabolic abnormalities, and fortification of dairy products with phytosterols and ω-3 fatty acids seems to be a good approach to improve cardiometabolic risk biomarkers. In conclusion, the systematic reviews and meta-analyses of the present supplement support adequate milk consumption at various stages of life and in the prevention/control of various noncommunicable chronic diseases.

Introduction and Executive Summary of the Supplement, Role of Milk and Dairy Products in Health and Prevention of Noncommunicable Chronic Diseases: A Series of Systematic Reviews.

The hypocholesterolemic effect and the modification of serum biomarkers of a dietary plant sterol (PS) intake, cholesterol precursors and cytokines after the consumption of milk-based fruit beverages with a milk fat globule membrane were evaluated by a randomized, double-blind, crossover, multiple dose bioavailability study. Postmenopausal women (n = 38) consumed daily 250 mL of a beverage with or without 2 g of PS added during 6 weeks in each of the study periods. With the intake of the PS-added beverage, significant decreases (mg dL-1) in serum total cholesterol (pre-treatment: 220.0 ± 27.8 vs. post-treatment: 212.9 ± 25.8; p < 0.05) and LDL-cholesterol (129.4 ± 28.5 vs. 121.7 ± 24.4; p < 0.05) were detected. The cholesterol precursor lathosterol (11.2%), markers of the dietary PS intake (campesterol 43.1% and β-sitosterol 32.5%), and anti-inflammatory IL-10 cytokine (22.5%) increased significantly, with a concomitant significant reduction in pro-inflammatory IL-1β (6.7%). No variations in HDL-cholesterol, other sterols (desmosterol and stigmasterol) or cytokines (IL-6, IL-8, IL-12p70 and TNF-α) were detected. These results indicated that this kind of PS-enriched milk-based fruit beverage is suitable during the period of clinical intervention, and its consumption may be an adequate way to improve PS functionality since a significant reduction in cholesterol levels has been observed. Therefore, the intake of this beverage could contribute to reduce the risk of cardiovascular disease also obtaining a beneficial effect on the serum inflammatory status in postmenopausal women.

A positive impact on the serum lipid profile and cytokines after the consumption of a plant sterol-enriched beverage with a milk fat globule membrane: a clinical study.

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