FOR HEALTHCARE PROFESSIONALS

How Supradyn works: Efficacy of multivitamin supplements

During demanding everyday challenges, an adequate supply of micronutrients is vital to maintain health and vitality.

Even in developed countries, where fresh, nutritious foods are plentiful, micronutrient levels regularly fall short of recommendations. Micronutrient supplementation may help the vital physiological processes that restore internal balance and aid recovery. The positive influence of Supradyn multivitamin supplements has been clinically studied and proven to increase energy production. Results of three separate independent clinical studies on the effects of Supradyn show that just one Supradyn tablet improves micronutrient status as well as physical and cognitive performance. The research has demonstrated that Supradyn effectively counteracts fatigue and increases total energy expenditure. An improvement in multitasking battery has also been noted with significant reduction in sleep disorders and autonomic nervous system symptoms, as well as lower frequency and intensity of headaches during supplementation. No adverse side effects have been observed in any clinical study with Supradyn.

Clinical studies on Supradyn®

Haskell et al. 2010

Study design

  • Randomized, double-blind, placebo-controlled, parallel-group study
  • 216 healthy females, aged 25–50 years, reporting occasional fatigue
  • Placebo vs. Supradyn 3RDA (daily intake for the duration of 62 days)

 

Methods

  1. Questionnaires on mood/fatigue/well-being
    • Mood measures: Medical outcome study quality of life Short-Form 36 (SF-36), Chalder fatigue scale, profile of mood states (POMS), state trait anxiety inventory (STAI)
    • Mood scales: Bond-Lader mood scales, visual analogue scales (VAS)
  2. Computerized multi-tasking

    Multi-tasking framework with 4 cognitive tasks (2x20 mins on day 1 and 62): mathematical processing (5 mins), stroop colour-word (5 mins), highest number (5 mins), and memory search task (5 mins)

    • Mathematical processing: series of addition calculations (three-figure sums).
    • Stroop colour-word: showed words in different colors describing colors (e.g. red, green, blue), indicate the color of the printed word (ignore the meaning of the word)
    • Highest number: presented digits between 0 and 9 in a grid, indicate the highest digit in the grid
    • Memory search: 4 letters are presented for 4 s. Following, every 10 s a single letter appears and participants have to indicate whether it appeared in the original list of the 4 letters or not.
  3. Physiological parameter
    • Homocysteine
    • 8-hydroxy-2'-deoxyguanosine (measure of oxidative damage)

 

Study results

  1. Questionnaires on mood/fatigue/well-being
    • Significant attenuation of the increased ratings of physical tiredness after 62-day supplementation of Supradyn vs. Placebo.
    • Trend towards an attenuation of the reduction of alertness after 62-day supplementation of Supradyn vs. Placebo.
    • No effects of treatment on SF-36, Chalder fatigue scale, or POMS. Completion of the multi-tasking framework, irrespective of treatment, led to an overall reduction in subjective alertness, contentment, calmness, and an increase in anxiety, mental & physical tiredness.
    • No significant treatment-related effects on negative change in mood/fatigue during completion of the multi-tasking framework.
  2. Computerized multi-tasking
    • Significant increase of accuracy across all 4 multi-tasking framework tasks during the first assessment (trend towards the same effect during the second assessment)
    • Higher accuracy of responses in the mathematical processing and stroop colour-word task in the Supradyn group during both assessment on day 62.
    • Faster completion of the mathematical processing task in the Supradyn group during both assessment on day 62.
    • Faster completion of the stroop colour-word task in the Supradyn group during the second assessment on day 62.
    • Higher accuracy of responses in the memory search task in the Supradyn group during the first assessment on day 62.
    • Faster completion of the memory search task in the Placebo group during the second assessment on day 62.
    • No significant differences on the highest number tap task.
  3. Physiological parameter on day 62
    • Reduction in homocysteine levels in the Supradyn group
    • Homocysteine is a toxic by-product product of one-carbon metabolism, it may contribute to neurodegenerative disorders may be related to cognitive functioning
    • Elevated homocysteine levels are an indicator of vitamin deficiency, as vitamins are needed to remethylate it (make it non-toxic)
    • No effect on levels of 8-hydroxyl-2'-deoxyguanosine. 8-OHdG represents a measure of oxidative DNA damage and has previously been shown to be sensitive to both chronic and acute stress.

Maric et al. 2014

Chronic Fatigue Syndrome (CFS)

  • ME/CFS is characterized by severe chronic fatigue lasting for at least 6 months, including clinical symptoms such as tender cervical or axillary lymph nodes, muscle pain, joint pain without swelling or redness, post-exertional malaise for more than 24 hours and unrefreshing sleep.4
  • The fatigue may worsen with physical or mental activity but does not improve with rest5
  • The cause of CFS is poorly understood6
  • Lack of effective therapeutic treatment5
  • Prevalence: 10-15% in the general population worldwide6
  • CFS can impair quality of life (QoL), social, and occupational areas of life6
  • Accumulated data suggest a link between oxidative stress (biomarkers) and CFS6

 

Why studying CFS in association with supplementation of a MVM product (e.g. Supradyn)?

  • Causes of CFS are diverse and not 100% researched at the moment. However, accumulating evidence suggest that oxidative stress plays a prominent role in CFS. By treating CFS patients with antioxidants (as contained in MVM products), it might be possible to reduce the oxidative stress to a level where the symptoms of CFS can be alleviated/improved.

 

Study design

  • Open-label, non-controlled study
  • 36 females, aged 18-50 years, diagnosed with chronic fatigue syndrome (CFS)
  • Supradyn 3RDA (daily intake for the duration of 2 months)
  • Questionnaire assessment before and 8 weeks after commencing treatment

 

Methods

  1. Questionnaire assessment
    • Fibro Fatigue Scale (FFS): 12-item questionnaire assessing symptom severity in patients with CFS (e.g. aches, fatigue, concentration difficulties, etc.) on a scale from 0 (absence of symptom) to 6 (maximum degree of symptom)
    • Quality of Life (QoL) Questionnaire: 36-item questionnaire widely used to measure disability in CFS research. It assesses the impact of illness on everyday physical, psychological, and social functioning
  2. Physiologial parameter
    • Superoxide dismutase (SOD) in the plasma

 

Study results

  1. Questionnaire assessment
    • Fibro Fatigue Scale (FFS): Significant decreases in fatigue, sleep disorders, autonomic nervous system symptoms (such as increased sweating, cold hands and feet, dry mouth, dizziness, breathing difficulties, palpitations, and frequent micturition), frequency and intensity of headaches, and subjective feeling of infection were observed.
    • Quality of Life: No significant influence of any aspect of health-related quality of life.
  2. Plasma parameter after 2 months
    • Improvement in SOD (superoxide dismutase) activity levels (313.81 mEq vs. 70.53 mEq). In our study, we found a significant decrease in SOD activity after the treatment. We also found several significant correlations between quality of life measures (physical function, physical role, bodily pain, vitality, and mental health) and SOD activity, but only after treatment. This is one of the reasons we believe a drop in SOD activity may be an indication of normalized SOD activity.
      • Low SOD activity level indicate oxidative stress which is known to play a prominent role in the development of chronic fatigue syndrome (CFS).
      • A normalization of antioxidant enzyme activity might be effective to improve the symptoms of CFS.

Kennedy et al. 2016

Study design

  • Randomized, double-blind, placebo-controlled, parallel-group study
  • 97 healthy females aged 25-49 years
  • Placebo vs. Supradyn 1RDA + CoQ10 or Supradyn 3RDA (daily intake for the duration of 56 days)
  • Placebo vs. Supradyn 1RDA + CoQ10 or Supradyn 3RDA (daily intake for the duration of 56 days)Two different Supradyn doses were tested to analyze if ascending doses have an effect

 

Methods

  1. Metabolic parameter with indirect calorimetry (ICa)
    • A mask covering the nose and mouth of the study subjects measured oxygen uptake and carbon dioxide production from the expired air. These data are used to calculate total energy expenditure, fat, and carbohydrate metabolism.Energy expenditure is the amount of energy (usually measured in kcal) which is burned by the body for every physical and mental process (e.g. breathing, digesting food, walking, solving cognitive tasks,...).
  2. Cerebral flood flow (CBF) with near-infrared spectroscopy (NIRS)
    • A non-invasive brain imaging technique which measures the concentration of total hemoglobin (oxygenated and deoxygenated). These data are used to calculate the cerebral blood flow (CBF).CBF was assessed, because the brain is by far the most metabolically active organ in the body, local blood-supply is needed for neural activity and thus cognitive functioning.
  3. Physiological parameter
    • Serum/plasma concentration of homocysteine, vitamin C, vitamin D, vitamin E, iron, zinc, and coenyzme Q10.
  4. Computerized cognitive tasks
    • 5 cognitive tasks of graded difficulty (25 mins on day 1 and 56): Serial 3s (5 mins), serial 7s (5 mins), serial 17s (5 mins), 3-back (5 mins), stroop colour-word (5 mins)
    • One control task (5mins)
  5. Questionnaires on subjective difficulty and mental fatigue
    • Mood scales: visual analogue scales (VAS)
    • Difficulty ratings: Bond-Lader mood scales

 

Study results

  1. Metabolic parameter with indirect calorimetry (Ica)
    • Fat oxidation: Significant increase following a single dose of the 3RDA treatment on day 1. No significant differences after 8 weeks administration for either active treatment (1RDA or 3 RDA).
    • Total energy: Significant increase of energy expenditure during task performance on day 1 and 56 in the 3RDA treatment group.
    • Carbohydrate oxidation: No significant difference between the active treatment (1RDA or 3 RDA) and placebo on either day.
  2. Cerebral blood-flow (CBF) parameter with near-infrared spectroscopy (NIRS)
    • Significant increase of total hemoglobin and CBF during 4 of the five cognitive tasks on the first day of treatment in the 1RDA group.
    • No significant difference associated with the 3RDA treatment on day 1 or day 56.
  3. Physiological parameter on day 56
    • Significantly higher vitamin D3 levels in the 1RDA and 3RDA treatment group vs. Placebo.
    • Significantly lower homocysteine levels in the 1RDA and 3RDA treatment group vs. Placebo.Elevated homocysteine levels are an indicator of vitamin deficiency
    • Significantly higher CoQ10 levels in the 1RDA treatment group vs. 3RDA treatment group and Placebo.
  4. Computerized cognitive tasks
    • No significant differences in task performance on day 1 or day 56 on either active treatment. This could be attributable to several factors: comparatively small study with lessthan 30 participants/group (as opposed to over 100/per group in the Haskell et al. study showing cognitive benefits of supplementation  with Supradyn; the participants wore a restrictive head gear and a face mask potentially introducing physical or psychological noise into the data; no baseline for the cognitive outcomes, that could be used as a covariate, thus reducing the sensitivity of the assessment.
  5. Questionnaires on subjective difficulty and mental fatigue
    • No significant effects on ratings of either mental fatigue or task difficulty following a single dose of 1RDA or 3RDA.
    • No significant effects on ratings of mental fatigue on day 56 for any active treatment (1RDA or 3RDA).
    • No significant effects on the Bond-Lader mood scales or Energy VAS.
    • 1RDA and 3 RDA treatment group perceived the 3-back task difficulty significantly higher on day 56 vs. the Placebo group.

Dodd et al. 2020

Study design

  • Randomized, double-blind, placebo-controlled, parallel group study
  • 91 healthy males and females aged 18-35 years, young regular exercisers, intended to treat population
  • Placebo vs. Supradyn 3RDA + CoQ10 (daily intake for the duration of 28 days)

 

Methods

  1. Metabolic parameter with indirect calorimetry (ICa)
    • A mask covering the nose and mouth of the study subjects measured oxygen uptake and carbon dioxide production from the expired air. These data are used to calculate total energy expenditure, fat, and carbohydrate metabolism.
    • Energy expenditure is the amount of energy (usually measured in kcal) which is burned by the body for every physical and mental process (e.g. breathing, digesting food, walking, solving cognitive tasks,...).
  2. Physical exercise
    • 30 min graded treadmill run: 20 min identical velocity followed by graded increases every 2 min
  3. Computerized cognitive tasks
    • "Cognitive Demand Battery" (CDB) comprising of 3 cognitive tasks (30 mins on day 1 and 28): Serial 3s (2 mins), serial 7s (2 mins), rapid visual information processing (5 mins)
    • Serial 3s: start with number between 800 and 999, always subtract 3
    • Serial 7s: start with number between 800 and 999, always subtract 7
    • Rapid visual information processing (RVIP): showed numbers between 1 and 9 on screen, identify series of three odd or three even numbers
    • 3 series of the three tasks
  4. Questionnaires on subjective energy, stress and fatigue ratings
    • During physical exercise: participants marked a subjective scale (BORG scale from 6-20; 6=no exertion at all, 20=maximal exertion), displayed on a tablet before and at 10, 20, 30 mins during the exercise
    • During cognitive tasks: Participants were asked to indicate their current levels of “mental stamina”, “physical stamina” and “concentration” on scale from “very low” to “very high”; and “stress” on a scale from “not at all” to “extremely”, before and at 10, 20, 30 min during the cognitive battery
  5. Physiological parameter
    • Measured in a subgroup of participants
    • Venous blood samples were taken at rest, immediately following exercise, following cognitive tasks, and at 24 and 48 h post-exercise

    Recovery biomarkers

    • Protein carbonyls (measure of cell oxidation)
    • F2-isoprostanes (measure of cell oxidation)
    • Glutathione peroxidase (measure antioxidant activity)
    • Interleukin 6 (measure for inflammation)
    • C-reactive protein (measure for general damage)

    Micronutrient status and homocysteine levels

    • serum ferritin (indicator of iron storage)
    • vitamin B12
    • creatinine (waste product produced by muscles)
    • homocysteine (is a toxic by-product of the one-carbon metabolism)
    • homocysteine

 

Results

  1. Metabolic parameter during physical exercise
    • Total energy: Significantly higher energy expenditure during physical exercise in males receiving Supradyn vs. Placebo.
    • Micronutrients play a crucial role in the functioning of mitochondria as the major producer of ATP (the energy currency of the cells). Performance of physical exercise require more effort and energy from the body than simply doing nothing. The increase of measured energy expenditure after supplementation with Supradyn suggests that Supradyn contains micronutrients useful for the cells for the generation of ATP to meet the higher energy demand.
    • Carbohydrate oxidation: Significantly higher carbohydrate oxidation following 30 mins of physical exercise in males receiving Supradyn vs. Placebo. No significant differences in carbohydrate oxidation in females receiving Supradyn at any point vs. Placebo.
  2. Metabolic parameter during cognitive tasks
    • Total energy: Significantly higher energy expenditure during cognitive tasks in the Supradyn group vs. Placebo.
  3. Subjective mental fatigue/tiredness ratings during physical exercise
    • Significantly lower mental tiredness ratings in the Supradyn vs placebo group during physical exercise on both day 1 and day 28
  4. Subjective physical tiredness/perceived exertion ratings during physical exercise:
    • Significantly lower perceived exertion during physical exercise in the Supradyn vs. placebo group, both on day 1 and day 28
    • Significantly lower physical tiredness ratings in females in the Supradyn vs placebo group during physical exercise on both day 1 and day 28
  5. Subjective stress ratings during cognitive tasks:
    • Significantly lower stress ratings following each repetition of the cognitive tasks in females of the Supradyn group vs. Placebo group.
  6. Recovery biomarkers on day 28
    • Significantly increased ferritin level in Supradyn group vs. Placebo group at Day 28.
    • Trend towards decreased homocysteine level in Supradyn vs. Placebo group at Day 28.
    • Trend towards increased vitamin B12 level in Supradyn vs. Placebo group at Day 28.
    • Recovery biomarkers are not reported due to small sample size.

 

REFERENCES

  1. Neumann, MA, Simmer, K and Gibson, R. A. A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled trial. Pediatrics, 2000. 105(1); 32-38.
  2. Ryan, AS and Nelson, EB. Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clin Pediatr (Phila). 2008. 47(4): 355-62.
  3. SanGiovanni, JP, Parra-Cabrera, s. et al. Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants. 2010. Pediatrics 105(6): 1292-8.
  4. Simmer, K. and Patole, S. Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Systematic Reviews (1): CD000375. 2004
  5. Simmer, K, Schulzke SM, et al. Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Systematic Reviews (1): CD000375. 2008
  6. Maggini S and Spitzer V. Ginseng and micronutrients for vitality and cognition. In: Watson RR and Preedy VR (eds.). 2013. Bioactive Food as Dietary Interventions for the Aging Population, pp. 277-303. San Diego: Academic Press.

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