Why was the study done?
Vitamin C and vitamin D insufficiency are very prevalent in hospitalized patients, and both vitamins have been linked to psychological abnormalities, including abnormal mood states. Researchers suspected that supplementation might therefore improve mood in hospital in-patients.

How was the study carried out?
This was a small double-blind clinical trial in 55 subjects randomized to either vitamin C (500mg twice daily) or vitamin D (1000 IU twice daily). Reasons for hospitalizations were mixed, and ranged from cancer to cardiovascular disease, diabetes, renal failure and gastrointestinal disease. Before and after 5-10 days of supplementation, participants completed a mood assessment questionnaire using a well validated 30-item questionnaire – the Profile of Mood States (POMS-B). Assessments of mood state were carried out at the beginning and end of the study by the same researcher and at the same time of day. Patients had blood samples drawn to assess their Vitamin C and D status.

What were the results?
Patients with plasma total concentrations of vitamin C less than 28.4 μmol/L were considered vitamin C depleted, while those with concentrations less than 11.4 μmol/L was considered deficient. For vitamin D, blood levels of 25-hydroxy D less than 75 nmol/L was considered deficient.

Fifty-six percent of the vitamin C group had plasma concentrations less than 28.4 μmol/L, while 9% were deficient (<11.4 μmol/L). Eighty-one percent of the vitamin D group had 25-hydroxy D levels less than 75 nmol/L. Vitamin C supplementation for an average of 8.7 days more than tripled plasma vitamin C (P<0.0001) and this was associated with a 34% reduction in total mood disturbance scores (P=0.013). Vitamin D supplementation for an average of 7.5 days increased plasma levels by 20% (p<0.0004). However, vitamin D supplements did not raise 25-hydroxy D into the target normal range (75 nmol/L) and had no effect on mood scores.

What conclusions did the researchers come to?
The researchers concluded that treatment of low plasma vitamin C, so prevalent in hospitalized patients, improved their mood state. Because they saw no response to vitamin D supplementation, the effect of vitamin C on mood is likely to be a real effect, and not simply a placebo response.

Usually, the earlier you find a cancer the sooner you treat it the better the outcome. But current practice is not to treat CLL at the early stages but wait until symptoms develop before offering chemotherapy. This is because clinical studies have found no advantage in early treatment. But this watch-and-wait approach can be hard for patients to handle and many diagnosed with the early stages of CLL feel powerless because there seems to be nothing they can do to help themselves.

Now a new study from the Mayo Clinic provides hope that there is something very important that such patients can do to help prevent progression – they can make sure that their blood levels of vitamin D are high. Researchers found a significant difference in cancer progression and death from CLL in patients with sufficient vitamin D in their blood compared to those who did not. They also found that the higher the starting vitamin D level a patient had, the longer the survival, whereas decreasing blood levels, as is common at northerly latitudes during the winter months, predicted shorter intervals between diagnosis and progression of leukemia.

If you have been diagnosed with CLL and are in the wait-and-see patient category, work with a knowledgeable physician or health care practitioner who will test your blood for 25-hydroxy D – the storage form of vitamin D in blood and a reliable indicator of vitamin D status – and make sure you take enough vitamin D to keep you in the cancer protective range.

Click here to watch a video made by one of the Mayo Clinic researchers involved in this research: www.youtube.com/watch?v=VOOFljuXtgI

Reference:Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia (CLL).Shanafelt TD et al. Blood. 2010 Nov 3. [Epub ahead of print]

Not according to a new study which found that probiotics did survive in the freezer under usual storage conditions [1]. A previous study of probiotic ice cream found that regular consumption of probiotic ice cream increased the numbers of good bacteria and also reduced the number of potentially harmful streptococcal organisms in the mouth [2]. So probiotic ice cream might be a good thing, except for the extra calories and sugar you would be consuming if you ate it every day. But for an occasional treat it may be an improvement on the standard confection. Otherwise, for a daily intake of probiotics, stick to yogurt or (calorie-free) supplements.

References:

1. Production of functional probiotic, prebiotic, and synbiotic ice creams.
Di Criscio T et al. J Dairy Sci. 2010 Oct;93(10):4555-64.

2. Short-term effect of ice-cream containing Bifidobacterium lactis Bb-12 on the number of salivary mutans streptococci and lactobacilli.
Caglar E et al. Acta Odontol Scand. 2008 Jun;66(3):154-8

After a run-in period of 6 weeks on a standardized diet, 62 patients were randomized to receive either simvastin alone, or simvastin plus omega 3 fats. Fifty subjects completed the 6-week prospective, randomized, open-label study, with 7 drop outs in the combination therapy group and 5 in the simvastatin-only group.  In the omega-3 plus statin group there was an average decreases in triglyceride levels of 41.0 percent, compared to 13.9 percent in the statin only group. Additionally, there were significant reductions in LDL cholesterol levels in both groups, while HDL levels (“good” cholesterol) were not affected by either intervention.

While those results might look good on the surface, they may not tell the whole story.  The purpose of conducting clinical trials like this one is to inform clinical decision making and correctly identify therapies that are beneficial, non beneficial, or harmful. Optimal therapy would be the treatment or combination of treatments that gave the best results with fewest side effects that was also cost effective.

What we do not know from this study is what would have been the outcome if high dose omega-3 fats had been tested alone. A more scientifically rigorous study would have included a third intervention group: High dose omega-3 fats alone. As it stands, we do not know if the dose of omega-3 fats used in this study – about three times the standard dose commonly recommended for prophylactic use – would have outperformed the statins alone, and be as good, or even better than the combination treatment.

So, without testing each of the components used in this trial separately we cannot conclude that statins combined with fish oil is the optimal treatment for dyslipidemias.

Reference: Kim SH, et al. Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability. Eur J Clin Nutr. 2011;65(1):110-6.

Researchers followed nearly 1000 men and women for 9 years to see if those who gained weight or whose waist circumference increased over that period would be more likely to become diabetic. After adjustment for other risk factors at baseline, increases in both waist circumference and weight were individually found to be associated with increased incidence of diabetes.

The surprising thing was that the risk of becoming diabetic was greatest in those who had normal BMI* (>25 Kg/m²) at the start of the study. For them, an increase in BMI or waist size over the next few years increased the likelihood of becoming diabetic by nearly 80 percent. Note that a normal waist measurement in less than 35” for women and under 40” for men.

“It is important to monitor and prevent increases in waist circumference, in particular for those with BMI<25 kg/m²,” the study authors write.

* BMI is a measure of a person’s weight in relation to height, and you can calculate yours at many sites on the internet. A BMI of 19-25 is considered normal, 26-30 is considered overweight, and a BMI greater than 30 is obese. Waist measurement should be taken at or just below the belly button. Use a mirror or get someone to check that you keep the tape measure straight while measuring.

Reference:Increases in waist circumference and weight as predictors of type 2 diabetes in individuals with impaired fasting glucose: influence of baseline BMI: data from the DESIR study. Gautier Aet al. Diabetes Care. 2010 Aug;33(8):1850-2

Now this excellent paper points out that laboratory animals are not healthy to begin with. Compared to their free-living counterparts they are sedentary, obese, glucose intolerant, and on a trajectory to premature death. The authors point out that failure by researchers to recognize this may lead to errors in the interpretation of the outcome of studies.

Reference: “Control” laboratory rodents are metabolically morbid: why it matters. Martin B, Ji S, Maudsley S, Mattson MP. Proc Natl Acad Sci U S A. 2010;107(14):6127-33

Why was the study done?

As distance from the equator increases, serum levels of 25-hydroxyvitamin (25-(OH)D), the storage form of vitamin D, fall during the winter months. Since fall and winter are peak seasons for colds and flu, it has been speculated that higher circulating levels of 25-(OH)D may increase resistance to infection and conversely, lower levels in the winter would increase vulnerability. The study was done to see if there was a link between circulating blood levels of 25-(OH)D and the incidence of acute viral respiratory tract infections.

How was the study carried out?

During the fall and winter of 2009-2010, blood levels of 25-(OH)D were tested monthly in 198 healthy adults, who were not informed as to what substance was being measured in their blood. Investigators tracking the development of any acute respiratory tract infections were not aware of the participants’ serum 25-hydroxyvitamin D concentrations. At the end of the study the incidence of infection in participants with different blood levels of 25-(OH)D was determined.

What were the results?

In this study, those who supplemented with vitamin D, or had light skin pigmentation, and those with lean body mass generally had higher concentrations of 25-(OH)D. Blood levels of 38 ng/ml (about 98 nmol/L) had a significantly reduced risk (p<0.0001) of developing acute respiratory tract infections, and a marked reduction in the percentages of days ill.

What conclusions did the researchers come to?

By maintaining a blood level of 25-(OH)D of around 100 nmol/L or higher, those living in temperate zones could significantly reduce colds and flu during the fall and winter. The researchers call for future studies examining the efficacy of vitamin D supplementation to reduce the incidence and severity of specific viral infections, including influenza, in the general population. They also suggest that those known to have generally lower circulating levels of 25-(OH)D such as pregnant women, dark skinned individuals, and the obese might be particularly helped by supplementation.

AILEEN’S COMMENTARY

The findings of this study confirm what vitamin D researchers have long suspected: It is not just coincidence that we suffer more from coughs and colds during the winter months. Increased susceptibility is likely to be related to the fact that circulating blood levels of vitamin D plummet as summer memories fade and winter sets in.

This was an observational study done in adults, and the researchers have not yet confirmed their hypothesis in intervention studies, where the effect of supplementing vitamin D over the winter months is compared with placebo to see if vitamin D supplements reduce risk of winter colds and flu in healthy adults. However, other recent studies suggest that boosting wintertime vitamin D with supplements above current recommended daily intakes might indeed be beneficial, and is unlikely to be harmful.

Vitamin D supplements prevent seasonal flu in school-age children

A recently published study gave Japanese schoolchildren either 1200 IU vitamin D3 or placebo from Dec ‘08 – March ’09 and tracked the incidence of seasonal influenza A.¹ The diagnosis of flu was correctly made – that is, in the laboratory – by examining nasal swabs for evidence of the virus. This is important, as so often a diagnosis of flu is made based on the presence of symptoms alone. And since the symptoms of flu may be confused with those of colds or allergy, it is critical in this type of research that an accurate laboratory diagnosis is made.

In this study, Influenza A occurred in 18/167 (10.8%) of the children on vitamin D(3) supplements compared with 31/167 (18.6%) on placebo. As a secondary outcome, children included in the study who also suffered from asthma were followed to see if supplementing with vitamin D had any positive effect on the number and severity of asthma attacks over the winter. They found a significant reduction in asthma exacerbations among children taking the vitamin D supplements.

Vitamin D and innate immunity

So how might vitamin D work to protect against colds and flu? In healthy individuals, immune cellspatrol tissues,seeking out pathogens. This is our first line of defence against infection and is known as the innate immune response. Molecules on the surface of immune cells – toll-like receptors – sense the presence of strings of amino acids common to a wide range of potentially infective organisms, but foreign to our own tissues. Innate immunity is particularly important to enable us to fight viruses like Clostridium difficile and other microbes to which we have not previously been exposed.  The presence of toll-like receptors on the surface of our cells depends on adequate vitamin D stores. ²

Clostridium difficile-associated diarrhea is an increasingly common infection often first encountered in a hospital setting. It can be difficult to control.  A recent study among hospitalized patients with confirmed C. difficile infections showed that infected patients were less likely to clear the infection within 30 days when they had low vitamin D levels. Moreover, mortality rates from any cause were also higher – there was a 56% increase in mortality in patients with low vitamin D compared with 33% for those with serum 25(OH)D levels of 21 ng/dL (52 nmol/L) or above.

The study was presented recently as an abstract at a meeting (Digestive Disease Week 2010). So the findings should be considered preliminary until the full paper is published in a peer-reviewed journal. The effect of supplementing patients with low vitamin D and recovery from C. difficile infection also remains to be seen.

Other nutrients are required for a healthy immune response

Following activation of the innate immune response by vitamin D dependent mechanisms, other nutrients such as the antioxidant vitamins A, C and E, and the minerals manganese, selenium and zinc also come into play.

Once a pathogen is identified, the immune system begins the elaborate process of disabling and eliminating it. First the pathogen is engulfed and ingested by immune cells (phagocytes), and then it is killed by rapid bursts of free radicals, also known as reactive oxygen species (ROS). As well as disarming invading pathogens ROS also injure host tissues, and this produces the nasty symptoms of flu – the sore throat and achy joints.³ If left unchecked the ROS response also damages immune cells, prolonging symptoms.⁴ The antioxidant vitamins and minerals work synergistically to neutralize free radicals,⁵ and good tissue stores of antioxidants are therefore needed to prevent such tissue injury.⁶

There are some interesting studies from the late 1980s where the transmission of influenza between family members over the winter months was tracked. What these studies showed was that not everyone who gets a virus ends up sick. Some individuals, although shown to be infected and harbouring the virus managed to remain symptom free.⁷ One has to wonder if these individuals were lucky enough to have higher tissue stores not only of vitamin D, but also antioxidants.

Are higher than recommended doses of vitamin D safe in pregnancy?  

Pregnant women are vulnerable to infection during pregnancy, and it has been suggested that intakes of vitamin D higher than recommended might be helpful for mother and baby. But the issue is controversial and raises issues of safety. The Canadian Paediatric Society suggests pregnant women take 2000 IU of vitamin D daily, while the American Academy of Pediatrics recommends 200 IU a day, a 10-fold difference. But are higher levels safe? Recent research suggests they are not only safe but prevent many complications of pregnancy.

Carol Wagner, MD, of the Medical University of South Carolina in Charleston and colleagues enrolled 494 pregnant women in a randomized trial of three daily doses of the vitamin – 400, 2,000, and 4,000 IU a day – to see if higher doses reduced complications of pregnancy,⁸ and also to test the safety of each dose. Not only were all doses shown to be safe, but the highest dose – 4000 IU per day – was associated with reduced rates of pre-term labor, pre-term birth and infection, as well as higher blood levels of vitamin D levels in the newborns. According to Carol Wagner, pregnant women can safely take 4,000 International Units a day and would benefit from so doing.   

Reference

1. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Urashima M et al. Am J Clin Nutr. 2010 May;91(5):1255-60

2. 1-alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR 2 and TLR4 in vitro. Scherberich JE, Kellermeyer M, Ried C, Hartinger A. Eur J Med Res. 2005 Apr 20;10(4):179-82

3.  Herman Award Lecture, 1995: infection-induced malnutrition–from cholera to cytokines. Beisel WR. Am J Clin Nutr.1995 Oct;62(4):813-9.

4. Reactive oxygen species in immune responses. Grisham MB. Free Radic Biol Med. 2004 Jun 15;36(12):1479-80.

5. Increased antioxidant capacity in healthy volunteers taking a mixture of oral antioxidants versus vitamin C or E supplementation. Lara-Padilla E et al. Adv Ther. 2007 Jan-Feb;24(1):50-9

6. Effects of dietary antioxidants on the immune function of middle-aged adults. Hughes DA. Proc Nutr Soc.1999 Feb;58(1):79-84.

7. Influenza B in households: virus shedding without symptoms or antibody response. Foy HM et al. Am J Epidemiol. 1987;126(3):506-15

8. Wagner CL et al. “Vitamin D supplementation during Pregnancy Part I, NICHD/CTSA Randomized Clinical Trial (RCT): Safety Considerations” PAS 2010; Abstract 2630.7

The product used was a high dose B-complex, with 500mg of vitamin C plus the minerals calcium (100mg), magnesium (100mg) and zinc (10mg).  Many of these nutrients are in short supply in typical modern diets and all of them are known to be critical for optimal brain and central nervous system functioning. The participants received either placebo or the multi-vitamin/mineral supplement in identical effervescent tablets each morning for 1 month.

Before the study began all participants received a battery of tests designed to assess their self reported stress levels, and the mental fatigue that is induced by the continuous repetition of cognitively demanding tasks. The same tests were repeated at the end of the study and the effect of treatment on mood, mental fatigue, accuracy and speed of performance was assessed. The assessments were repeated  after a state of fatigue was induced, either by continuous repetition of a complex cognitive task or by physical activity.

At the end of the study the vitamin/mineral group rated themselves as less ‘mentally tired’ both before and after completion of the battery of cognitive tests. Supplementation led to improved ratings of stress, mental health and vigour, and improved performance under mental and physical stress. All the components in the active intervention were water soluble, and these essential nutrients therefore need to be replaced on a daily basis. B-vitamins, vitamin C, zinc and magnesium are also nutrients that are very vulnerable to depletion by stress.

Until now, studies evaluating the relationship between vitamin and mineral supplementation and psychological functioning have been in the sick or the elderly.  So it is refreshing to see such studies being carried out in younger, healthy individuals. The researchers conclude that healthy members of the general population may benefit from higher levels of vitamins and minerals through direct dietary supplementation.

Reference: Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Kennedy DO et al. Psychopharmacology (Berl). 2010 July; 211(1): 55–68.

Researchers led by Dr. Bonnie Kaplan at the University of Calgary in Alberta were concerned about swallowing problems because of potential dropout rates in clinical trials. So they developed and published a method to train children in how to swallow pills¹. They have also produced a video showing their methods. It should be useful to adults too. Check out the video at  http://www.ucalgary.ca/research4kids/pillswallowing

1. Successful treatment of pill-swallowing difficulties with head posture practice

BJ Kaplan, RA Steiger, J Pope, A Marsh, M Sharp, SG Crawford Paedriatr Child Health 2010;15 (5):el-e5

Researchers at the Cleveland Clinic Bone Clinic wondered why it was that some of the patients with vitamin D deficiency failed to increase their vitamin D blood levels (25-hydroxy D) when put on supplements and retested 2-3 months later.  Normally, when you start to take vitamin D supplements, blood levels slowly climb and then plateau. Continuing on with the same dose of vitamin D will not substantially increase blood levels after this point.

So the researchers asked a group of vitamin D non-responders to take their usual vitamin D supplement with the biggest meal they ate each day. After 2-3 months average serum 25 hydroxy D levels had increased from 76.25 nmol/L +/- 11.75 (30.5 +/- 4.7 ng/mL) to 118 +/-  27.25 nmol/L (47.2 +/- 10.9 ng/mL), an increase of more than 50%. The patients were on a variety of doses of vitamin D ranging from 1000-50,000 IUs a day. But the dose didn’t seem to matter, as the approximate improvement in vitamin D status was similar for all.

And the improvements were not just seen in patients with bone disorders (osteoporosis or osteopenia). Researchers report that similar increases were observed with a wide range of vitamin D doses taken for a variety of medical conditions.

Reference: Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25-hydroxyvitamin D. Mulligan GB, Licata A. J Bone Milner Res. 2010;25(4):928-30