Mineral, vitamin, and phytopharmaca supplements are often used in treating the common cold because they are believed to improve the patient's immune system and accelerate healing. However, not all doctors know whether this action is supported by adequate scientific evidence.

Benefits and Science Evidences of 6 Vitamin and Supplements in Treating Common Cold

The common cold is a general term for upper respiratory tract diseases caused by various viruses and is a self-limited disease. The duration of common cold episodes can reach ten days. Common cold symptoms can include nasal congestion, rhinorrhea, sneezing, sore throat, cough, low-grade fever, headache, and malaise. 

For most people, the common cold is self-limiting. But in some patients, the common cold has some complications, such as sinusitis, lower respiratory tract infections, acute asthma exacerbations, and acute otitis media.

Studies show that maintaining the body's immune system in normal conditions affects shortening the duration, reducing the incidence and the severity of the common cold. Many supplements are currently on the market, including zinc, vitamin D, vitamin C, Echinacea, Elderberry, and Phyllanthus niruri, which are often used in treating the common cold.

1. Vitamin C

Vitamin C has antioxidant properties and anti-inflammatory, which are thought to help manage the common cold.

Vitamin C and the Immune System

A study conducted by Lauer et al. showed that oral administration of vitamin C 100 mg daily for four weeks can increase the effect by 22% of radical scavenging effects on the human skin's physical barrier.

In another study, vitamin C's administration increases the lung inflammatory cell activity in bronchial asthma patients, decreases neutrophil superoxide production, and provides a therapeutic effect in pancreatitis cases. Potential mechanisms for these effects are increased antioxidant ability, blockade of lipid peroxidase in plasma, and improved cellular immune function.

However, other studies do not find vitamin C's effect on natural killer cells or act as a countermeasure for oxidation and immune changes in marathon runners.

In the aspect of adaptive cellular immunity, a study of 30 elderly patients hospitalized for a long, found that vitamin C supplementation for 28 days could improve cell-mediated immune function in terms of absolute T, T4, T4 to T8 ratio, and lymphocyte proliferation to response Phytohemagglutinin (PHA) when compared with the placebo group.

Scientific Evidence of Vitamins C for Common Cold

A meta-analysis by Hemila et al. in 2013 of 29 RCTs (11,306 participants) revealed that regular vitamin C supplements of at least 200 mg per day did not significantly impact common cold incidence in healthy populations. However, there was a decrease in common cold incidence in extreme physical stress (598 marathon runners or skiers, or soldiers). For the duration and severity of symptoms, regular vitamin C supplements affect, although small, decreasing common cold duration by 8% in adults and 14% in children.

In another study by Maggini et al. using 1000 mg of vitamin C combined with 10 mg of Zn, the combination of vitamin C and Zn appeared safe and more effective in reducing rhinorrhea symptoms in the common cold than the placebo within five days of intervention.

2. Vitamin D

Vitamin D receptors are expressed in many immune cells. Various studies have reported that Vitamin D plays an immunomodulator on innate immunity and the adaptive immune response.

Vitamin D and Immune System

Active vitamin D or 1,25 (OH) 2D3 plays a role in gene regulation via the hydroxylase enzyme, which codes for proteins needed at tight junctions (e.g., occludin), gap junctions, and adherent junctions (e.g., E-cadherin). Vitamin D plays a role in cathelicidin and defensins production, which play a role in the initial defense (physical barrier).

Active vitamin D (vitamin D3) increases phagocytosis, both immunoglobulin-mediated and complement-mediated in human monocytes, through stimulation of monocyte maturation into macrophages. The Hewison et al. report showed that increased serum vitamin D levels in tuberculosis patients increased monocyte phagocytosis and beta-amyloid degradation.

Human epidemiological studies indicate that vitamin D supplementation is associated with independent protective factors against autoimmune events mediated by T helper 1 (Th 1). Vitamin D can reduce Th1 / Th17 cells and related cytokines, increase regulator T cells (Tregs), downregulate T cell-driven IgG production, and inhibit dendritic cell differentiation.

Scientific Evidence of Vitamin D for Common Cold
Research shows that vitamin D supplementation helps prevent upper respiratory tract infections, including the common cold. Laaksi et al. conducted a randomized controlled trial in 164 men in Finnish military training. This trial showed that the adjusted hazard ratio for the number of absences due to upper respiratory tract infection was lower in the intervention group given 400 units of vitamin D per day compared to placebo (HR 0, 71).

Similar results were found in a 2012 meta-analysis of 5 clinical trials. This study found that upper respiratory tract infections were lower in the vitamin D group than controls (odds ratio 0.582). The dose of vitamin D used ranges from 800-2000 units per day.

A post hoc analysis study conducted by Bergman et al. in 2015 indicated that high vitamin D levels were associated with lower upper respiratory tract infection risk (RR 1.3). Vitamin D levels above 100 nmol / L are associated with a higher likelihood of having good health.

In the pediatric population, a study in Mongolia found that supplementing milk fortified with 300 IU of vitamin D3 reduced acute respiratory infection risk in the winter compared to a group of children with vitamin D deficiency. In another study by Urashima et al., 1200 unit supplementation/day of vitamin D3 in school-age children can reduce the common cold incidence caused by influenza A.

3. Zinc

Zinc and the Immune System

Adequate zinc (Zn) helps maintain the mucous membrane's physical barrier and integrity, affecting cellular components of innate immunity, such as phagocytosis of macrophages and neutrophils, natural killer cell activity, and on cytosolic defense against oxidative stress. The transcription factor of the Gfi1 repressor (Zn finger protein) has been identified as an immune response regulator.

In vitro data indicate that Zn can normalize interleukin production by macrophages in inflammatory conditions such as IL-2, IL-1, IL-6, and tumor necrosis factor-alpha. Zn also modulates releasing cytokines by nuclear blood cells (such as neutrophils) in the peripheral and gamma interferon production.

Zn is needed for antigen presentation via major histocompatibility complex class II (MHC-II) in initiating an adaptive immune response. Zn is also an essential cofactor for the thymic hormone ( thymulin). 

In animal experiments, Zn deficiency is associated with low thymus weight and T lymphocyte cells' progressive loss due to a lack of thymulin. The Zn ion directly affects the lymphocyte membrane, which influences the maturation and differentiation of T lymphocytes. Zn also controls the humoral immune response mediated by antibodies through Zn-membrane-localized transporter (ZIP10-Zn), regulating early B cell development and maintaining B cells mature.

In viral infection cases,  the blockade of the Intercellular Adhesion Molecule 1 (ICAM-1) receptor mediates the direct antiviral effect of Zn (5 mg). ICAM-1 plays a vital role in rhinovirus entry in the nasal epithelium. Other in vitro reports indicate that zinc (Zn2 +) with pyrithione can interrupt SARS-CoV-GFP and other RNA viruses replication.

Scientific Evidence of Zinc for Common Cold

Some studies show that Zn supplementation reduces pneumonia and common cold risks, especially in the elderly and children. Zn supplementation given within 24 hours of the common cold onset for up to 7 days was reported to decrease common cold duration by about 1 day than the placebo group (Odds ratio 0.45).

In a meta-analysis conducted by Singh and Das in 2011, it was found that pooled results from 10 randomized controlled clinical trials (RCTs) showed a shorter duration of common cold symptoms than the placebo in terms of the therapy group.

In the pooled result of 5 RCTs, the Zn supplement reduced the severity of symptoms in patients who received Zn supplement with a standard effect size of 0.39. Meanwhile, for preventive purposes, the pooled result from 2 studies showed that Zn supplementation reduced the common cold incidence compared to placebo (Incidence rate ratio 0.64). Zinc supplements used in this meta-analysis are zinc gluconate lozenges and zinc sulfate syrup.

The meta-analysis results were confirmed by another meta-analysis conducted on 7 RCTs (575 participants with common cold) in 2017. The meta-analysis results showed that the common cold average duration was 33% shorter in the group that received zinc supplementation.

Subgroup analysis found that zinc gluconate supplementation was as effective as zinc acetate lozenges. This meta-analysis found no evidence that Zn doses above 100 mg/day are more effective for common cold therapy than the lower doses. 

Commonly reported side effects are bad taste, nausea, and anosmia. There are no specific recommendations regarding dosage guidelines or preparations for Zn preparation for common cold management.

4. Echinacea

Echinacea is a phytopharmaca with immunomodulatory potential that has been widely studied.

Echinacea and the Immune System

Echinacea extract has an immunomodulatory character because it can increase phenotypic and dendritic cells functional maturation via activation of JNK, p38-MAPK, and NFkB pathways murine and human dendritic cells.

In the study of Vimalanathan et al., E.purpurea extract was reported to reduce the expression of ICAM-1 (Intercellular Adhesion Molecule 1), fibronectin, and platelet-activating factor receptors that play a role in bacterial entry and adhesion. In the cytokine aspect, E.purpurea is reported to inhibit inflammatory hyperstimulation (cytokine storm) by suppressing the expression of NFkB or TLR-4.

In animal models, Echinacea can regulate cytokine levels, including interleukin-6 (IL-6), IL-10, and IL-17, as well as mRNA expression due to the cytokine response in the spleen. The immunomodulatory effect in healthy humans is confirmed by the findings of the pilot study Dapas et al.

Echinacea has also affected adaptive cellular immunity. In mouse models, supplementation with Echinacea has been shown to increase the percentage of CD4 + and CD8 + T lymphocyte cells in the blood. Research by Fonseca et al. found that a water-soluble extract from Echinacea purpurea (L.) Moench showed a dose-related adjuvant effect on human T cells. The mechanism is estimated by the increased mobilization of Ca2 + and T cell activity.

Scientific Evidence of Echinacea for Common Cold

Randomized controlled studies conducted on 755 healthy subjects given E.purpurea extract for four months showed that Echinacea supplements could reduce the number of common cold episodes and reduce the duration of the common cold the need to use pain relievers. Besides, Echinacea could also inhibit virally confirmed common colds and specifically prevent enveloped virus infection (P <0.05).

Aside from E.purpurea, a study in Pierro et al. in 2012 found that E.angustifolia root extract increased the immune response caused by influenza vaccination. The 2014 Cochrane Review comparing Echinacea with placebo (4631 participants) showed a positive trend regarding Echinacea's effect on common cold care, but the results were not statistically significant. These results were followed up by a meta-analysis conducted by Schapowal et al. in 2015. From 6 clinical trials (2458 patients), the use of Echinacea extract was reported to be associated with a reduced risk of acute or common cold, respiratory infections (RR 0.649).

5. Elderberry

Elderberry is one of the phytopharmaca that has been widely used as an herbal medicine for anti-inflammatory, diuretic, and the common cold. The most famous is the black elder or Sambucus nigra L. The active compounds in elderberry are flavonoid components, including flavonols, proanthocyanidins, anthocyanins, and phenolic acids.

Elderberry and the Immune System

In experimental animals, elderberry extract was shown to have high complement fixation activity, inhibition of hemolysis, and inhibition of nitric oxide (NO) production. In vitro, experimental data found that S. nigra can:

  • modulate proinflammatory cytokines IL-1 and TNA-alpha, 
  • increase basophil secretion for IL-4, IL-13, and histamine
  • influence the neutrophil function 
  • Inhibit the release of proinflammatory cytokines and phosphatidylinositol 3 -kinase from macrophages. 

The results above indicate the immunomodulatory potential of elderberry extract.

In vitro reports found that elderberry extract (S.nigra) inhibited the growth of Helicobacter pylori, Streptococcus pyogenes, apart from the immunomodulatory effect Streptococcus groups C and G, Branhamella catarrhalis, and Haemophilus influenza. In vitro reports also show that S. nigra extract can inhibit the herpes simplex virus and influenza A and B viruses, including the H1N1 strain. In vitro data indicate that S. nigra prevents influenza infection by competitive inhibition with the influenza virus to bind the virus to the target cell.

Elderberry Scientific Evidence for Common Cold

There have been many studies examining the effect of S. nigra on the common cold. A randomized controlled study in 1995 (27 adult patients with common cold) found that in the group of patients who received S.nigra extract, recovery from fever was faster than in the control group (4 days vs. 6 days), and symptoms improved faster (2 days vs. 5 days).

Meanwhile, another study in 2004 with a greater number of patients (60 adult patients with common cold) found that the group of patients who received S.nigra extract showed a faster improvement of symptoms than the control group (2-4 days vs. 7- 8 days). However, it should be underlined that the number of samples in these studies is minimal.

However, a study by Tiralongo et al. in 2016 found no statistically significant difference between the treatment group receiving elderberry extract and the control group in terms of symptom improvement and disease duration, even though the data showed a positive trend of more improvement in the therapy group.

A meta-analysis presents the most recent data from Hawkins et al. in 2019 (180 patients). The quantitative effects synthesis found a large mean effect size (ES) of 1,717 for a decrease in duration and ES of 2,074 to relieve common cold symptoms in patients receiving elderberry extract. Side effects often reported in the use of elderberry extract are nausea, vomiting, diarrhea, and allergic reactions.

6. Phyllanthus niruri

Phyllanthus niruri is a tropical plant known to have many pharmacological benefits, such as immunomodulators, antibacterial, antiviral, diuretic, antihyperglycemic hepatoprotective.

Phyllanthus niruri and the Immune System

P. niruri extract is reported in animal models to strengthen immune system components' activity and function, such as stimulating Natural Killer cell cytotoxicity, TNF-alpha secretion by T helper 1, and reducing IL-10 secretion by T helper 2.

Correspondingly, Nworu et al. reported that the liquid extract of P.niruri is a mitogenic lymphocyte potential in murine and can induce a significant increase in the expression of surface activation marker (CD69) and proliferation of T and B lymphocytes. In stimulated naïve splenocyte cultures, P extract .iruri can increase both gamma interferon and IL-4 production. Even phagocytosis, lysosomal enzyme activity, and TNF-alpha in macrophages in murine bone marrow have increased, including macrophages' release of nitric oxide.

Scientific Evidence of Phyllanthus niruri for the Common Cold

Scientific evidence that examines the effect of P.niruri extract on the common cold is still limited. Kusumaningrum et al. conducted a randomized controlled trial on 100 children with an age range of 2-6 years with the common cold. The results found no significant difference in the common cold severity between the treatment and control groups.