Keith Ong describes the results from his study on the effects of multiple intravenous injections of vitamin C and glutathione on the skin of 283 patients.

As a person ages, hormonal changes cause intrinsic aging, while the external environment, primarily ultraviolet (UV) radiation, accounts for much of the extrinsic aging1,2. Intrinsic aging of the skin results in the thinning of the epidermis, a reduction in the connective tissue matrix, and a reduction in sebaceous glands. Therefore, even without UV radiation exposure, as a person ages, their skin will look thinner, paler, more wrinkled, and drier. Genetically, men have a thicker epidermis, connective tissue matrix, and higher sebaceous gland density, therefore the signs of intrinsic aging tend to be less pronounced compared to a woman of the same age.

UV irradiation leads to extrinsic skin aging by inducing the production of reactive oxygen species (ROS) in the skin3. In time the ROS generate a cascade of molecular reactions that result in mutation and destruction of collagen, elastin, proteoglycans, and other dermal cellular structures4. Macroscopically, this ROS-induced damage will make an individual’s skin look dry, wrinkled, dull, sallow, and unevenly pigmented5. UV irradiation also triggers melanogenesis, hence resulting in skin darkening and pigment formation. Vitamin C (Vit C) and glutathione (GSH) are strong antioxidants. Their strong antioxidant property helps to protect the skin against UV radiation induced photoaging4–7 by eradicating the ROS, hence halting the destructive cascade of activities. Vit C and GSH also help to whiten the skin by inhibiting melanogenesis, triggered by UV irradiation9–12. Vitiman C also triggers a strong reparative effect in the skin by inducing a quantitative increase and qualitative improvement of collagen molecules thereby reversing the UV induced skin damage4.

In summary, UV irradiation produces ROS and triggers melanogenesis, which causes the skin to become dry, dull, and unevenly pigmented. Vitamin C and glutathione remove the ROS, repair the skin connective tissue, and inhibit skin darkening, thereby making the skin more hydrated, fairer, and more radiant4–7, 9–12.

Vitamin C and glutathione

For these reasons, Vit C and GSH are commonly found in topical cosmetic creams for skin repair and whitening3,8. Farris published a review article3, which stated that a significant level of scientific research supports the use of topical vitamin C for collagen synthesis, photoprotection from ultraviolet A and B, skin lightening, and improvement of a variety of inflammatory dermatoses3. In a double blind and placebo controlled clinical trial involving 30 adult Japanese women over a period of 10 weeks conducted by Fumiko et al8, the subjects applied glutathione 2% lotion to one side of the face and a placebo lotion to the other side twice daily for 10 weeks. Fumiko et al reported significant skin melanin index reduction, significant increase in moisture content of the stratum corneum, a suppression of wrinkle formation, and improvement in skin smoothness.

Besides using topical cream, intravenous injection containing Vit C and GSH has also been used for skin hydration and whitening in many parts of Asia, particularly in the Philippines, Taiwan, China, and Malaysia. This was the first reported study to evaluate the skin hydrating and whitening effects of Vit C and GSH given in the form of intravenous injections.

Aim of study

The aim of the study was to evaluate the skin hydrating and whitening effects of Vit C and GSH by reporting patients’ assessment and overall satisfaction after a course of six Vit C and GSH injections. For this study, skin hydration referred to making skin less dry and more moist. Skin whitening referred to making skin either fairer or more radiant or both.

Material and method

Study participants

The medical records of consecutive patients newly enrolled between 1 st January to 31 st December 2014 were selected for this study. Inclusion criteria were:

  • First visit for Vit C and GSH injection fell between 1 st January 2014 to 31 st December 2014
  • Completed six Vit C and GSH injections
  • Of the six Vit C and GSH injections, the interval between each injection must be equal or less than 10 days.

Screen Shot 2015-10-14 at 14.55.57Material used

The vitamin C solution used for injection was under the brand Laroscorbine® 1 g/5 ml (Bayer Sante Familiale, larosrcobine, Gaillard, France). The glutathione powder used for injection was under the brand Tationil® 600 mg/4 ml, (Teoforma , Tationil, Salimbene, Italy).

Method of injection

One vial of glutathione powder (600 mg) was mixed with 10 ml of vitamin C solution (2 g) in a 10 ml syringe. The constituted glutathione/vitamin C solution was injected intravenously into the patient via a Surflo® winged infusion set 23G x 3/4” (Terumo Corporation, Surflo®, Tokyo, Screen Shot 2015-10-14 at 14.56.05Japan). The constituted solution was injected slowly over 5 minutes.

Injections sites were either right cubital fossa, left cubital fossa, dorsum of right hand or dorsum of left hand. The same doctor constituted the solution and administered the injection to the patient.

Treatment protocol

Patients were given an injection once every 7–10 days, a total of six times. The first injection was given during the first visit and assessment.

Method of assessment

Skin assessment of the face and all limbs at first visit was noted clinically by visual assessment and the patient’s main complaints were recorded. For the purpose of the study, the skin parameters were divided into:

  • Normal hydration or dry
  • Fair or tan
  • Radiant or dull.

The first Vit C and GSH injection was given during the first visit. During the second to sixth visit, the patients reported on how they felt about their skin condition over the period of time from the last injection up to the current visit to the clinic. Patients reported whether their skin conditions were worse than before, less dry, fairer, more radiant, or no change (Table 1). One month after the sixth visit, a research assistant contacted the patients over the phone to get their feedback on the entire treatment. Patients were asked to score their satisfaction level on their skin improvement based on a score of 1 to 7, 1 being the least satisfied and 7 being the most satisfied.

Subjective definition of skin parameters as understood by patients

Patients commonly perceived dry skin as having fine creases/wrinkles on the skin, feeling dry, feeling itchiness easily, mild peeling, scattered erythematous patches or having scratch marks appear on the limbs easily.

They commonly complained of darker tanned skin, in relation to their previous lighter skin tone.

Patients commonly described dull skin as sallow and yellowish in tone. They wanted a more radiant skin tone, which they describe as whitish-pink, baby-like skin.

Results

A total of 313 patients were enrolled in the study. However, 30 patients were excluded because the interval between injections was more than 10 days. Thus, the total number of patients included in the present study was 283. The median age of the 283 patients was 33 years old and 269 were female (Table 2). The majority of the patients were Chinese (n=228, 80.6%), while 30 (10.6%) were Malay, 10 (3.5%) were Indian, and 15 (5.3%) were of other ethnicities.

Screen Shot 2015-10-14 at 15.00.54Screen Shot 2015-10-14 at 15.01.04

 

 

 

 

 

 

 

 

 

During the first visit, most patients (n=115) complained of dry and dull skin, followed by 58 patients complaining of dry, dull, and tanned skin (Table 3).

During the second visit, patients were asked to feedback on how they felt about their skin over the period of time from after the first injection up to the second visit at the clinic. A total of 206 (72.8%) patients reported noticeable improvement, their skin was less dry, more radiant, fairer or combinations. Of the 206 patients, most (n=168) reported that their skin was less dry, 60 reported more radiant skin, and 38 reported fairer skin. In total, 77 (27.2%) patients claim no noticeable improvement (Table 4).

From the second to sixth visit, the number of patients that reported noticeable skin improvement increased from 206 (72.8%) to 270 (95.4%). At the sixth visit, the most common skin improvement was skin being less dry, followed by more radiant and fairer. At the sixth visit, only 13 (4.6%) patients did not notice any improvement.

One month after the sixth injection, the feedback score obtained from the patients showed a median score of 4.99 and most patients (n=90, 31.8%) reported 5 on the scale of 1 to 7 (Table 5).

Screen Shot 2015-10-14 at 15.01.13Of the 283 patients, only three complained of mild gastritis, two complained of chills, and two complained of headache. There was no severe complication noted in this study.

In 7 years of administering Vit C and GSH injections, the author realised that after each treatment protocol patients returned either monthly for maintenance injections or some patients returned for further injections after they came back from hot sunny overseas trips where their skin became tanned and dried.

The author concluded from practical experience that the duration of treatment results depends on three important factors:

  • Environmental UV light exposure (for example, an outdoor job vs indoor job)
  • Amount of protection against UV light (patients were advised to carry an umbrella when walking under the sun)
  • Genetic conditions (patients with eczema tend to visit the clinic monthly for maintenance).

Discussion

Most patients (n=270, 95.4%) perceived a certain degree of skin hydration and whitening after six Vit C and GSH intravenous injections and most patients (mean score 4.99 out of 7) were satisfied with the results. This supported the popular claim in Asia that Vit C and GSH injections had strong skin hydrating and whitening effects.

This study showed that the skin enhancement and whitening effects of Vit C and GSH injection were dose and time dependent. Most patients experienced improved skin hydration first, followed by increased radiance and fairness. The number of patients experiencing skin being less dry, more radiant and fairer also increased steadily from the second visit to the sixth visit (Table 4). This demonstrated that the efficacy of the Vit C and GSH was dependent on the number of injections received and some patients might require more than six injections to reach optimal skin enhancement whereby they felt that their skin was hydrated, fair, and radiant. This might also infer that improved skin hydration was the first step for skin repair and after adequate hydration, the skin will further improve to look more radiant and fairer (whitening effect).

A person’s skin hydration, radiance, and tone varies daily and even within the day itself. This variation is due to multiple factors such as the level of stress, amount of sleep, amount of sun exposure, working environment, hormonal cycle, and diet. Therefore, in this study, the author reported how the patients felt about their skin conditions over the period of time between the injections, rather than just reporting on their skin conditions during the time of visit.

To date, from the manufacturer’s published literature and a search on the Internet, the author found no contraindication for intravenous GSH injection. No side-effect has been reported from intermittent dose, short-term GSH supplementation.

Screen Shot 2015-10-14 at 15.06.10The contraindications for intravenous Vit C supplementation is glucose-6-phosphate dehydrogenase (G6PD) deficiency13 and chronic renal failure14. The author would also like to highlight that in 2000, the recommended dietary allowance (RDA) set the tolerable upper limit (UL) of Vit C at 2000 mg daily, referencing its laxative effect as the reason for establishing the UL15. In this paper, the patients were given 2000 mg of intravenous Vit C, once a week. The author would like to emphasize that there was no issue of Vit C overdose in the context of this study.

 

 

Some patients had raised the concern regarding the formation of kidney stones due to a high dose of vitamin C supplementation. Their concerns can be traced back to a Swedish study by Thomas LD et al16, involving 23,355 Swedish men taking oral vitamin C supplements with a follow-up of more than 10 years. The results indicated that high-dose ascorbic acid are associated with a dose-dependent two-fold increased risk of kidney stone formation among men. Thomas LD et al also mentioned in the study that their result cannot be extrapolated to women, because men intrinsically have a higher chance of experiencing kidney stones.

Screen Shot 2015-10-14 at 15.06.25

 

 

 

 

 

 

 

 

 

 

 

To address the patients’ concern, the author highlighted that the Thomas LD et al study is based on oral Vit C supplementation (1000 mg per tab) taken consistently, over a long period of time (>10 years) and the study cannot be extrapolated to women. In this article, the whitening injection treatment protocol involves intravenous Vit C (2000 mg) and GSH (600 mg) injection given only once a week, over a period of 6 weeks. The absolute amount of vitamin C taken and the duration of the whitening injection treatment protocol totally differs from the Thomas et al study cohort.

Conclusion

Most patients (n=270, 95.4%) perceived a certain degree of skin hydration and whitening after six Vit C and GSH intravenous injections and most patients (mean score 4.99 out of 7) were satisfied with the results, without experiencing any serious adverse event.

More studies could be conducted to evaluate the efficacy of intravenous Vit C and GSH injections, especially on the areas of skin whitening, post-operation wound healing, repair of second and third degree burns, and repair of photo-aged skin.