Professional Documents
Culture Documents
pharmaceutical
applications
Executive summary
Micronutrients play a critical role in overall nutrition and health. This studies demonstrate the benefits for specific groups when they take
is highlighted by the plethora of continuous research published in high dose vitamins. Studies also show that vitamins taken in
high profile scientific journals focused on the benefits of vitamins and pharmaceutical applications support human health.
minerals. However, evidence shows that many people worldwide fail
This whitepaper explains the role and importance of vitamin dietary
to meet recommended intake levels. The impact of low micronutrient
reference intakes (DRIs) and draws on the latest clinical data to show
intake is a major public health concern, resulting in vulnerability to
the benefits of vitamin intake beyond currently recognized health
infection and disease.
effects and the nutritional range. Highlighting key studies, it also
Optimal intake is therefore essential to reduce these and other risks. describes the vital function of nutrition under clinical conditions and
But what is an optimal intake? Existing data indicates that there is a demonstrates the significance of drug-nutrient interactions on health.
need to revisit approaches to defining appropriate nutritional In addition, a summary of the use of vitamins in pharmaceutical
requirements for a variety of vitamins, such as vitamin E. Recent applications is provided.
January 2017
Vitamins for
pharmaceutical applications
Introduction
Emerging data suggest that intake of micronutrients in higher doses cognitive function.1,2 Understanding the role of vitamins beyond the
holds promise for roles beyond currently recognized health effects for nutritional range and their use in the pharmaceutical industry can lead
selected individuals and population groups. For example, research to the creation of innovative, safe and high quality products that will
shows that vitamin E protects essential fatty acids from lipid serve the interests of consumer health.
peroxidation and that improved vitamin E status is protective for
Page 2
Vitamins for
pharmaceutical applications
Community
Malnourished 6%
At Risk 32%
Wellnourished 62%
0 20 40 60
Rehabilitation
Malnourished 50%
91%
At Risk 41%
Wellnourished 9%
0 20 40 60
Page 3
Vitamins for
pharmaceutical applications
Malnutrition can
lead to increased:
The implications for malnourished patients does not always stop there. A recent study
investigated undernutrition and risk of mortality in elderly patients within one year of hospital • need of care;
discharge and found that being undernourished at the time of hospital discharge is an
• risk for infections;
independent risk factor for 1-year mortality in elderly patients. The severity of the nutritional
depletion was assessed using body mass index (BMI), weight loss indices, and arm • risk for complications
circumferences. Even after controlling for functional status and other indicators of illness (morbidity);
severity, the relationship between each of these nutritional indices and the outcome remained
• need for treatments in
significant — the more nutritionally depleted, the greater the risk. The study found indicators
hospitals;
of chronic nutritional depletion (e.g. low BMI and long-term weight loss) to be the best
predictors of post discharge mortality.7 • length of stay; and
survivorship function as
0.96 20-30 Million Europeans are
generated by the Cox
regression model for affected by malnutrition and
0.94
specific sets of covariate
values. The upper curve is
the cost for Europe is €120-170
for body mass index (BMI)
0.92 BMI (kg/m2) billion/year.8
> 20 kg/m2 with all of the > 20 (n = 455)
0.90
other independent
variables in the model set 0.88
Did you
equal to their population
means. The lower curve 0.86
know?
was produced in the same
manner except it is for 0.84
BMI <20 kg/m2. ≤ 20 (n = 205)
0.82
0 100 200 300 400 Nutritional management can
Days be introduced as
part of a medically supervised
diet to meet specific dietary
Reduced Factors predisposing
mobility
needs as a result of a disease
malnutrition and micronutrient
or condition. This management
deficiency can include poor
could help support optimal
Reduced capacity nutrient intake, caused by
to feed oneself Malnutrition patient health before, during
issues like having difficulty
eating, medication, depression
and after medical treatment
and dementia, as well as and subsequently help reduce
suboptimal nutrient utilization, predisposition to higher risk of
such as malabsorption or infection and mortality after
Loss of Apathy, depression, nutrient loss. In the elderly hospital discharge.
muscle mass reduced attention particularly, malnutrition is a
prevalent issue which can form
Reduced a cycle that is difficult to break
appetite if left untreated:
Figure 4
Page 4
Vitamins for
pharmaceutical applications
-15
***
†
-25 ***
Thiamine †
Percentage
concentrated pharmaceutical-grade vitamin B7 administered at a dose
60
Percentage
of 300 mg per day in the treatment of primary and secondary 40
progressive MS, a major area of unmet medical need.
40 ~3% ~50%
The vitamin B7 studied will require a chronic administration of a very 20 less less
high dose to treat patients with progressive MS, corresponding to ~3% ~50%
20
0 less less
10,000 times the recommended daily intake, which requires a
Total colds General Severe
pharmaceutical grade extra-pure source of vitamin B7.13 > 200mg population stress
0
Vitamin
Total C
colds + General
Vitamin C + Vitamin
Severe C
Vitamin C and cancer > 200mg population stress
Vitamin C + Vitamin C + Vitamin C
Despite the FDA not having approved the use of IV high-dose vitamin C
as a treatment for cancer, studies show that application of high-dose
Duration of common cold
IV vitamin C improved quality of life for cancer patients.14, 15
10
Improvements in physical, mental and emotional functions, symptoms Duration of common cold
of fatigue, nausea, vomiting, pain and appetite loss were 10
8
documented.16 In addition, a meta-analysis on vitamin C and breast
cancer indicates that post-diagnosis use of vitamin C supplementation 8
6
may be associated with a reduced risk of mortality.17
Days Days
New research demonstrates that cancer cells are much less efficient in 64
removing hydrogen peroxide than normal cells, and more disposed to ~1 ~1 ~1
day day day
damage and death from a high amount of hydrogen peroxide. This 24 less less less
explains why the high levels of vitamin C do not affect normal tissue, ~1 ~1 ~1
8%
day 14%
day 18%
day
but can be damaging to tumor tissue.18 2 less less less
0
Without 8%
Children 14%
Adults 18%
Children
Vitamin C and the common cold 0 Vitamin C > 200mg > 200mg 1–2g
supplement
Without Children Adults Vitamin
ChildrenC
The common cold is a viral infectious disease of the upper respiratory tract. Vitamin C > 200mg > 200mg 1–2g
Colds can lead to the upper respiratory system becoming less resistant Severity of supplement
the colds Vitamin C
to secondary bacterial infection, resulting in issues such as middle ear
Indicators of common cold severity:
infection, pneumonia, bronchitis, sinus infection or strep throat.19
• 0.1% less days indoors of off work or school (7 trials) (p=0.00035)
The body’s immune system can fight the infection after producing • 0.14% less on symptom severity score (9 trials) (p=0.0018)
antibodies, but there are currently no medicines that will cure the
• Total: 0.12% (p<0.00001)
common cold. However, there may be a way to reduce the risk of
contracting the common cold. A recent Cochrane meta-analysis shows
that vitamin C reduces the incidence, duration and severity of the
common cold when ≥ 200 mg/d is taken daily.20
Page 6
Vitamins for
pharmaceutical applications
Vitamin E and a range of health issues Figure 7: Results from ICARE study (Milman 2008)21
CVD 1.00
New research indicates that genotype matters also when it comes to
80
Event free survival (%)
α-tocopherol
60
40
Placebo
20
0
0 100 200 300 400 500 600 700
Days
Page 7
Vitamins for
pharmaceutical applications
Did you
EPA and DHA consumption for CVD patients know?
A systemic review and meta-analysis of the lipid-modulating effects of n-3 PUFAs combined • Lipid-lowering therapy with
evidences from 10 randomized controlled trials including 557 patients with end-stage renal statins can significantly
disease. Pooled analysis revealed that n-3 PUFA intake significantly reduced serum triglyceride
reduce the incidence of
levels by 0.78 mmol/L (95% confidence interval: -1.12 to -0.44 mmol/L, P < .0001).25
cardiovascular disease and
the risk of coronary events.
DSM is currently the only company in the world to hold both US DMFs
For further information, please visit:
and CEP certificates for all 13 essential vitamins. DSM offers its www.dsm.com/pharmaceuticalsolutions
pharmaceutical customers worldwide unparalleled sustainability of
Or contact: Kristina Cselovszky:
supply and speed to market, accelerating the registration process to get kristina.cselovszky@dsm.com,
products to market faster. With extensive experience in pharma-grade Business Development Director
vitamins, carotenoids and lipids Active Pharmaceutical Ingredients Pharma at DSM Nutritional Products.
(APIs), DSM provides customers with entirely customized support Manfred Eggersdorfer:
throughout every stage of a project. DSM’s full regulatory, scientific and manfred.eggersdorfer@dsm.com,
Senior Vice-President Nutrition
quality expertise and GMP-qualified production sites ensure that Science and Advocacy at DSM
projects are both safe and compliant. In addition to its strong IP Nutritional Products
portfolio, including carotenoids and DHA and EPA, DSM’s 400-strong
R&D team provide expertise in clinical trials. DSM also has a global
network of regulatory specialists, equipped to cater support in response
to customers’ local regulations.
For DSM, quality is a way of life. Quality for Life™ symbolizes quality,
reliability and traceability. This means that our customers are getting
the best ingredients, knowing the source on which they depend. Quality
for Life™ means sustainability. It is our commitment to our environment,
consumers, our business partners, our people and the regulatory
framework that governs our operations.
References
1 Traber et al, Vitamins C and E: beneficial effects from a mechanistic 11 Modified from Chobanian et al, The Seventh Report of the Joint 23 Ortega et al, Cognitive Function in Elderly People Is Influenced by
perspective. Free Radic Biol Med 2011 National Committee on Prevention, Detection, Evaluation, and Vitamin E Status. J of Nutr 2002
2 Witting et al, Effect of degree of fatty acid unsaturation in Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003 Sano et al, A controlled trial of selegiline, alpha-tocopherol,
tocopherol deficiency-induced creatinuria. J Nutr 1964 12 McNulty et al, Riboflavin, MTHFR genotype and blood pressure: or both as treatment for Alzheimer’s disease. The Alzheimer’s
3 Troesch et al, Dietary surveys indicate vitamin intakes below A personalized approach to prevention and treatment of Disease Cooperative Study. N Engl J Med 1997
recommendations are common in representative Western hypertension. Mol Aspects Med 2016 Dysken et al, Effect of Vitamin E and Memantine on Functional
countries. Br J of Nutr 2012 13 http://www.dsm.com/corporate/media/informationcente Decline in Alzheimer Disease: The TEAM-AD VA Cooperative
4 https://fnic.nal.usda.gov/sites/fnic.nal.usda.gov/files/uploads/ rnews/2015/06/2015-06-17-medday-and-dsm-announce- Randomized Trial. JAMA 2014
recommended_intakes_individuals.pdf apartnership-to-produce-pharmaceutical-grade-d-biotin-to- Mohajeri et al, Effects of Vitamin E on Cognitive Performance
treatprogressive-multiple-sclerosis.html during Ageing and in Alzheimer’s Disease. Nutrients 2014
5 Nutrition Day Conference 2010, Malnutrition and appropriate
nutritional care, Cornel Christian Sieber, Chair Geriatric Medicine 14 Padayatty et al, Vitamin C Pharmacokinetics: Implications for Oral 24 Traber et al, α-Tocopherol adipose tissue stores are depleted after
Friedrich-Alexander-University Erlangen-Nürnberg Institute for and Intravenous Use. Ann Intern Med 2004 burn injury in pediatric patients. Am J of Nutr 2010
Biomedicine of Aging Centre for Medicine of Aging Nuremberg 15 Fritz et al, Intravenous Vitamin C and Cancer: A Systematic Review. 25 Pei et al, The effect of n-3 polyunsaturated fatty acids on plasma
6 Kaiser et al, Frequency of Malnutrition in Older Adults: A Integrative Cancer Therapies 2014 lipids and lipoproteins in patients with chronic renal failure--a
Multinational Perspective Using the Mini Nutritional Assessment. 16 Yun et al, Vitamin C selectively kills KRAS and BRAF mutant meta-analysis of randomized controlled trials. J of Renal Nutr 2012
J of the Am Geriatrics Society 2010. Institute for Biomedicine of colorectal cancer cells by targeting GAPDH. Science 2015 26 Pirillo et al, Omega-3 polyunsaturated fatty acids in the treatment
Aging, Friedrich-Alexander University Erlangen-Nürnberg 17 Harris et al, Vitamin C and survival among women with breast of atherogenic dyslipidemia. Atherosclerosis Supplements 2013
7 Liu et al, Undernutrition and Risk of Mortality in Elderly Patients cancer: a meta-analysis. Eur J Cancer 2014 27 Miles et al, Influence of marine n-3 polyunsaturated fatty acids
Within 1 Year of Hospital Discharge. J Gerontol 2002 18 Doskey et al, Tumor cells have decreased ability to metabolize on immune function and a systematic review of their effects on
8 Nutrition Day Conference 2010, Malnutrition and appropriate H2O2: Implications for pharmacological ascorbate in cancer clinical outcomes in rheumatoid arthritis. Br J of Nutr 2012
nutritional care, Cornel Christian Sieber, Chair Geriatric Medicine therapy. Redox Biol 2016. 28 Genser, Food and drug interaction: consequences for the
Friedrich-Alexander-University Erlangen-Nürnberg, Institute for 19 http://medical-dictionary.thefreedictionary.com/common+cold nutrition/health status. Ann Nutr Metab 2008
Biomedicine of Aging Centre for Medicine of Aging Nuremberg
20 Hemilä H., Chalker E.: Cochrane Database Systematic Review 2013 29 McPartland et al, Update on Immunosuppressive Drugs Used in
9 Rabbani et al, High-dose thiamine therapy for patients with type Solid-Organ Transplantation and Their Nutrition Implications. Nutr
2 diabetes and microalbuminuria: a randomised, double-blind 21 Blum et al, Vitamin E reduces cardiovascular disease in individuals
with diabetes mellitus and the haptoglobin 2-2 genotype. Clin Pract 2007
placebo-controlled pilot study. Diabetologia 2009
Pharmacogenomics 2010 30 Herb, Nutrient, and Drug Interactions, 1st Edition Clinical
10 Horigan et al, Riboflavin lowers blood pressure in cardiovascular Implications and Therapeutic Strategies. Authors: Mitchell Bebel
disease patients homozygous for the 677C-->T polymorphism in 22 www.who.int / Sanyal et al. N Engl J Med, 2010 / Pacana et al. Curr
Opin Clin Nutr Metab Care, 2012 / Lomonaco et al. Drugs, 2013 Stargrove & Jonathan Treasure & Dwight L. McKee
MTHFR. J Hypertens 2010
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