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Vitamins for

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

Recommended intakes and requirements


Micronutrient
Figure 1: Micronutrient intake
intake panelpanel in Germany,
in Germany, US,
US, UK and theUK and NL
Netherlands
Vit A Vit D Vit E Thiamin Riboflavin Niacin Vit B6 Vit B12 Folic acid Vit C

Modern lifestyles may lead to suboptimal


vitamin intakes, even in affluent countries. A
Germany

recent study reviewed vitamin intakes in


Germany, the UK, The Netherlands and the
USA and compared the data with respective
national recommendations. Data on adults
from the most recently published national
United States

dietary intake surveys for the first three


countries and on adults from the US National
Health and Nutrition Examination Survey from
2003 to 2008 were used as a basis for the
analysis. The proportions of the populations
with intakes below recommendations were
United Kingdom

categorized as < 5, 5–25, >25–50, >50–75 and


>75 % for each vitamin. The data generated
are presented in a ‘traffic light display’,
illustrated in figure 1, using colors from green
to red to indicate degrees of sufficiency.
The Netherlands

The data was compared with the results from


the European Nutrition and Health Report
2009. The study demonstrated that, although
inter-country differences exist, intakes of several
<5% 5–2.5% 25–50% 50–75% >75% below recommendations

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Vitamins for
pharmaceutical applications

DRIs are used by healthcare


providers and government
vitamins are below recommendations in a large DRIs can play an important role in addressing
agencies to establish the
part of the population in each country. The nutritional inadequacies. Stakeholders across
guidelines for how much of
most critical vitamin appears to be vitamin D. the healthcare, nutrition and pharmaceutical
each nutrient an individual
industries can use DRIs and the latest clinical
The variation between the countries is most needs. The DRIs include four
evidence on the benefits of vitamins on
probably due to differences in types of information:
human health to understand appropriate
recommendations, levels of fortification
nutritional requirements for populations • Estimated Average
and local dietary habits. The findings
worldwide. They can then pave the way in Requirements (EAR)
demonstrate that a gap exists between
revisiting approaches to defining appropriate
vitamin intakes and requirements for a
dietary requirements and educating • Recommended Dietary
significant proportion of the population,
consumers on their health needs. Allowances (RDA)
even though diverse foods are available.3
• Adequate Intakes
• Tolerable Upper Intake Level4
Nutrition under clinical conditions
Nutrition inadequacies and malnutrition are even more prevalent under clinical conditions.
There is a particularly high prevalence of malnutrition and low vitamin intake in vulnerable Did you
populations, such as ill and or elderly patients, as well as patients recovering in hospitals and
other care facilities. Malnutrition for such patients can lead to a higher risk of infection and a
know?
longer time spent in hospital. Those affected by, or at risk of,
malnutrition in Europe:
Figure 2: Nutritional status of elderly persons in different settings6
• 5% of the entire population;
Hospital
Malnourished 39% • 10% in those over 65 years;
86%
At Risk 47%
• 15% in ages 75-80 living at
Wellnourished 14%
0 20 40 60
home;
Nursing Home • 35-40% of all hospital
Malnourished 14% admissions; and
At Risk 53%
• up to 60% in care homes.5
Wellnourished 33%
0 20 40 60

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

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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

1.00 • risk of dying from


diseases (mortality).
Figure 3 estimates of the 0.98
Predicted Probability of Survival

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

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Vitamins for
pharmaceutical applications

Examples of additional benefits


provided by vitamins in higher doses
Emerging scientific findings show the benefits of vitamin intake Vitamin B2 and CVD patients
beyond currently recognized health effects and the nutritional range
A recent study investigated 197 premature CVD patients, prescreened
for risk groups like elderly or people with certain malfunctions. The
for the MTHFR 677C-->T polymorphism, from an original cohort of 404
following examples highlight how a higher intake of nutrients beyond
to select those with the TT genotype (n = 60) and a similar number
nutritional requirements may provide additional benefits in defined
with heterozygous (CT; n = 85) or wild-type (CC; n = 75) genotypes. Of
groups; playing a part in supporting human health during illness. The
these, 181 completed an intervention in which participants were
diseases listed include diabetes, cancer, multiple sclerosis (MS),
randomized within each genotype group to receive 1.6 mg per day
cardiovascular disease (CVD), non-alcoholic fatty liver disease and
vitamin B2 (riboflavin) or placebo for 16 weeks. Among patients
Alzheimer’s disease. These are prevalent issues worldwide, affecting
taking one or more antihypertensive drugs at recruitment (82%), the
a significant number of people.
results show that target blood pressure (<140/90 mmHg) had been
Vitamin B1 and diabetic patients achieved in only 37% patients with the TT genotype compared with
59% with the CT and 64% with the CC genotype (P < 0.001).
There is evidence of thiamine (vitamin B1) deficiency in diabetics.
Vitamin B1 is important for maintaining a healthy nervous system and Vitamin B2 intervention reduced mean blood pressure specifically in
improving the cardiovascular functioning of the body. Its benefits those with the TT genotype (from 144/87 to 131/80 mmHg; P < 0.05
stretch further according to a new study. A high-dose therapy with systolic; P < 0.05 diastolic), with no response observed in the other
vitamin B1 in a rat model (experimentally induced diabetes in rats) genotype groups. The systolic blood pressure response to vitamin B2
prevented development of diabetic nephropathy, otherwise known as intervention in patients with MTHFR 677 TT genotype therefore
kidney disease. In humans, these preliminary results led to a double- demonstrates that genetically susceptible individuals may benefit the
blinded, placebo-controlled pilot study. In this study, high dose most from vitamin B2 supplementation. The study demonstrates that
vitamin B1 therapy was shown to reverse early stage diabetic it would take about 10 kilos of weight loss to achieve the blood
nephropathy – 300 milligrams (mg) vitamin B1 per day decreases pressure lowering that was reported by vitamin B2.10,11 The findings of
microalbuminuria. The use of vitamin B1 in this range is safe and the study may have important implications for the prevention and
further large-scale long-term clinical studies are still required. treatment of hypertension, especially as the TT genotype has a high
prevalence in many countries.12

Figure 5: Effect of thiamine on urinary albumin excretion (UAE) 9


Lifestyle factor SBP decreas (mmHg)
Study period (months)
0 1 2 3 4 5 Weight loss (per 10 kg) 5–20
0
Riboflavin (genotype-specific) 6–13
*
Change in urinary albumin (mg/24 h)

-5 *** * Physical activity 4–9


††
**
† Sodium reduction 2–8
-10 Placebo ***
Limit alcohol 2–4

-15
***

Did you know?


-20 ***

-25 ***
Thiamine †

-30 Elevated blood pressure is a leading risk for


Change from baseline of UAE in type 2 diabetic patients receiving Thiamine | Placebo.
death worldwide. Optimizing vitamin B2 status
Median values are shown: *p < 0.05 ** p < 0.01 *** p < 0.001 compared with baseline; offers a promising low-cost targeted strategy for
† p < 0.05 †† p < 0.01 compared with baseline change for the placebo. managing elevated blood pressure in genetically
at-risk groups.
Page 5
Vitamins for
pharmaceutical applications

Figure 6: Vitamin C may reduce the incidence,


Incidence of colds
duration and severity of a common cold20
100
Biotin (Vitamin B7) and MS patients Incidence of colds
100
80
A recent Phase III clinical trial on vitamin B7 and patients suffering from
progressive multiple sclerosis (MS) produced positive results. The
study found evidence of the efficacy and safety of a highly- 80
60

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

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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

Event free survival (%)


vitamin E; sub-populations with specific genetic makeup may profit 0.98
from this vitamin. A recent study into vitamin E and CVD showed that
vitamin E supplementation at a dose of 400 mg reduces and 0.96 HP 1-1 | Hp 2-1
normalizes the risk for cardiovascular events in diabetics with Hp 2-2: Vitamin E
Hp 2-2: Placebo
haptoglobin genotype 2-2 (Hp 2-2). The Hp gene exists in two variants, 0.94
the Hp1 and the Hp2 variant. In Western societies, 36% have Hp 2-2. Log-Rank P = 0.003
Diabetic individuals with Hp 2-2 have a marked increased oxidative 0.92
stress. Increased risk for cardiovascular events has been linked to Hp
2-2 genotype in diabetics. 0.90
0 100 200 300 400 500
Days

Non-alcoholic fatty liver disease Burns


Meanwhile, vitamin E has also been shown to reduce the risk of non- In a study to test whether burn injury reduces body stores of vitamin
alcoholic fatty liver disease, which is a prevalent and increasing issue E, α-tocopherol concentrations were measured in adipose tissue
worldwide, due to rising obesity levels. Data shows that samples. After receiving a burn injury, pediatric patients were
supplementation with vitamin E at a dose of 400 mg was superior to a assessed. Surgically obtained samples were taken at various
placebo for the treatment of nonalcoholic steatohepatitis in adults intervals and stored at −80°C in a biorepository. α- and
without diabetes.22 γ-Tocopherols, cholesterol, and triglycerides were measured in the
same tissue.
Cognitive health
The results found that the burn injury experienced by the pediatric
Vitamin E (at a dose of 2000 IU) has also been proven to delay
patients changed their metabolism so that vitamin E status
pathologies in Alzheimer’s disease – an age-dependent and
decreased during the month after injury. Further studies are needed
progressive neurological disease and the fourth-leading cause of
to evaluate the mechanism and consequences of the observed
death in industrialized societies.
vitamin E depletion. In addition, research on vitamin E
Figure 8: Alzheimer’s disease and vitamin E study: survival time supplementation in a higher dose in burn patients should be
without pathological “event”:23 undertaken to determine whether it could help restore the depleted
stocks of vitamin E in the body.24
100

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.

How should vitamins be used However, aggressive


lowering of lipids by statins
in pharmaceutical applications? comes with the risk of
decreasing EPA and DHA
So far, it is clear from emerging scientific In addition, certificates of suitability (CEPs) levels simultaneously. EPA
research that vitamins can go beyond and US Drug Master Files (DMFs) for essential and DHA can be considered
currently recognized health effects and the micronutrients are a necessary measure to as an alternative way to help
nutritional range, supporting human health in ensure that new products are developed to reduce plasma triglyceride
higher doses. Such clinical data and a clear be safe and of high quality for high dose levels and to beneficially
understanding of drug-nutrient interactions applications and specific claims. Pharma-grade influence the levels of other
must be used to define how vitamins should vitamins, carotenoids and lipids can be used blood lipids as well. Clinical
be used within the pharmaceutical industry. as Active Pharmaceutical Ingredients (APIs) trials have shown that EPA
Grading of Recommendations Assessment, to support the development of customized
and DHA as supplementation
Development and Evaluation (GRADE) is a solutions to suit specific applications.
is also effective when
method for assessing the quality of the
The pyramid (figure 9) shows the distinction added in combination with
evidence found for specific vitamins for use in
pharmaceutical applications. This can be
between general food and nutrition, other lipid-lowering drugs
specialist nutrition or dietary like statins.26
used as a reference, for example, by
supplementation and pharmaceuticals or
pharmaceutical and healthcare professionals. • Nonsteroidal anti-flammatory
prescribed medical treatments.
drugs (NSAIDs), such as
Aspirin, Ibuprofen and
Naproxen, can cause peptic
Rx
ulcus, diminish renal
function and impair Vitamin
OTC B6 metabolism. However,
they may have additive or
synergistic effects with certain
Dietary micro- or macronutrients, for
Supplements
example, to reduce pain. If an
adequate dose of EPA and
Fortification DHA (which have anti-
inflammatory properties)
is provided, NSAIDs might
be taken at a lower dose to
Nutrition
have a clinical benefit and
Figure 9
reduce potential side effects
of the drug.27
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Vitamins for
pharmaceutical applications

How to develop safe and customized treatments


Food-drug interactions are defined as with grapefruit juice and increase the risk of these agents to affect the nutrition status of
alterations of pharmacokinetics or adverse effects. The use of certain drugs may the transplant recipient. As many patients
pharmacodynamics of a drug or nutritional affect gastrointestinal (GI) tract function and undergoing transplantation are catabolic and
element or a compromise in nutritional status result in a loss of bodily electrolytes and fluid. vulnerable to malnutrition, it is particularly
as a result of the addition of a drug. Therefore, limiting drug prescriptions to important for carers of these patients to be
Pharmacokinetic is the word used to describe essential medications for as short a period as familiar with the nutrition implications of
when the absorption, distribution, possible and periodic re-evaluations of the immunosuppressive drugs.29
metabolism, or elimination (ADME) is altered. treatment chosen are needed to minimize
Comprehensive clinical data on the effects of
Meanwhile, pharmacodynamic refers to a adverse drug-nutrient interactions.28
combining pharmaceuticals with
situation where the pharmacological effects
The same study indicates that some people supplements can help companies understand
of two products are additive or oppositional.
are more at risk of nutritional compromise. how to develop safe, individualized treatment
Examples of where drug-nutrient interactions For example, elderly patients are particularly strategies for patients.30
occur include statins, contraceptives, proton at risk because more than 30% of all the
pump inhibitors, and cases where vitamins prescription drugs are taken by this Key take-away messages
have a synergistic effect with drugs. Drug- population. Failure to identify and properly
• Stakeholders across the
nutrient interactions can lead to a raising or manage drug-nutrient interactions can lead
healthcare, nutrition and
lowering of bioavailability of a nutrient induced to serious consequences. Other patients at
by drug intake. For example, according to a increased risk include those with cancer, AIDS pharmaceutical industries
study, drug-nutrient interactions can result in and organ transplant recipients. should use DRIs and the
reduced absorption of certain oral antibiotics. latest clinical evidence on the
Successful organ transplantation has become
This can lead to suboptimal antibiotic
the norm, now that improved
benefits of vitamins, EPA and
concentrations at the site of infection,
immunosuppressive agents have been DHA on human health to
increasing the risk of treatment failure. understand appropriate
introduced. The emphasis of
Nutrients can lead to an induction or inhibition immunosuppressive therapy has moved from nutritional requirements for
of enzymes in the gut, which may cause a preventing rejection to balancing acceptable populations worldwide
change in oral bioavailability of drugs or vice rates of rejection with moderation in adverse
versa. Grapefruit juice acts as a selective effects of the immunosuppressive agents.
• Emerging research suggests
intestinal CYP3A4 inhibitor, and can be used as According to scientific research, among the that micronutrient intake in
an example. The exposure of some drugs can many possible adverse effects of higher doses can play a role
be increased by more than fivefold when taken immunosuppressive therapy is the potential for beyond essentiality for
selected individuals and
population groups
Conclusion • Clinical data on the effects of
combining pharmaceuticals
Vitamins are essential micronutrients that the essentiality, can open up new opportunities in
with supplements can
body needs. The health of populations the pharmaceutical and healthcare industries.
worldwide can benefit from optimal intake. More investigation into the effects of
support development of safe
The review of recent clinical data heralds an micronutrient supplementation on health individualized treatment
exciting new phase for the role of vitamins in when used in combination with strategies for patients
pharmaceutical applications. The knowledge pharmaceuticals is needed, as well as a clear
• More investigation into the
that vitamins can play an important role in understanding on drug-nutrient interactions,
effects of micronutrient
patient health beyond their traditional part in to ensure optimal and safe patient treatment.
supplementation on health
when used in combination with
pharmaceuticals is needed
Page 9
Vitamins for
pharmaceutical applications

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

© DSM Nutritional Products 2017


Although DSM has used diligent care to ensure that the information provided herein is accurate and up to date, DSM makes no representation or warranty of the accuracy, reliability,
or completeness of the information. This white paper only contains scientific and technical information on the vitamins for pharmaceutical applications. Any explicit and/or
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