Researchers from the University of Sheffield partnered with industry to conducts a head-to-head clinical trial comparing the rate of change of vitamin D status in response to a vitamin D3 (3000IU per day) dose, in both capsule and oral spray (sublingual) methods of delivery.

Healthy volunteers took vitamin D over the course of six weeks in 2017 during the height of winter – a time when many people’s stores from the summer months are depleted.

Published in the European Journal of Clinical Nutrition the study concluded that the oral spray method of vitamin D was equally effective as taking a capsule and supported the same rate of improvement in vitamin D levels amongst the trial volunteers.

Dr Bernard Corfe, Senior Lecturer in Molecular Gastroenterology at the University of Sheffield and Principal Investigator for the trial, said: “All participants achieved adequate levels of vitamin D after just 21 days of using an oral spray, with those individuals who were considered severely deficient at the beginning of the trial (with levels lower than 25(OH)D) experiencing the most effective uptake of the supplement.”

A 2016 Scientific Advisory Committee on Nutrition report, highlighted the need for all UK adults and children to take a vitamin D supplement throughout the winter months, and the National Institute for Health Care Excellence extended this recommendation for children and young people to take a vitamin D supplement all year round.

“Vitamin D is essential to keep bones, teeth and muscles healthy, and is especially important for children’s development,” Dr Corfe added. “It’s difficult for people to get enough vitamin D through their diet, and during the winter the sun isn’t strong enough to help the body boost its levels.

“There is now more awareness of the need for people to supplement their vitamin D, but only around 40% of adults in the UK are considered to have sufficient levels. So this research is the opportunity to highlight the importance of this essential vitamin in supporting overall health, and in providing a valuable alternative source for those who may struggle to, or prefer not, to take tablets.”

Of the participants that expressed a preference, 70% said they preferred taking vitamin D by an oral spray for ease of use and better taste.

Dr Corfe said: “Often people can forget, or don’t want to take a daily supplement, especially those who take multiple medications. Children and people who have trouble swallowing due to medical conditions also can also have difficulty taking tablets, so to find that a spray is just as effective at raising people’s vitamin D levels provides a real alternative for those whose vitamin D levels are low.”

The scientists also implicate the neurodegenerative condition in a higher risk of depression, anxiety and a lower mean bone mass density (BMD) of the lumbar spine and femoral neck.

“These results indicate that vitamin D deficiency may play a role in Parkinson’s Disease [PD] pathogenesis, while vitamin D supplementation may be used to treat the non‐motor symptoms of PD,”​ says the team from Soochow University in China.

Initial findings

The team began by enrolling 182 patients with PD and 185 healthy controls. Serum vitamin D [25(OH)D] levels were measured along with BMD of the lumbar spine and femoral neck. They found that:

• Parkinson’s patients had significantly lower serum 25(OH)D levels relative to healthy controls
• Those with lower vitamin D levels had a significantly higher frequency of falls and insomnia
• They also had significantly more depression and anxiety
• People with Parkinson’s also had a significantly lower mean BMD of the lumbar spine and femoral neck

These findings remained true even after adjusting for  age, sex, and body mass index.

Symptoms of deficiency

Vitamin D deficiency is widespread in people with neurodegenerative diseases; studies showing around 55% of patients with Parkinson’s , 41% of those with Alzheimer’s have low levels – compared to 36% of a control population.

Vitamin D also has a vital role in bone metabolism and a lack of vitamin D which can help explain the increased risk of falls and fractures found in this study.

Studies have also shown that vitamin D levels are associated with cognition and mood in patients with Parkinson’s as well as gastrointestinal dysfunction, mainly delayed gastric emptying time.

Regarding the increase in falls, the authors write: “The most commonly cited theory for the connection between falls and vitamin D levels is related to reduced muscle mass and strength.”​

Connections between vitamin D, mood and sleep disorders are a little less clear.

The researchers also acknowledge a limitation of the study, having only evaluated 25(OH)D levels. An assortment of different sources of vitamin D, open up possibilities that different vitamin D forms may produce other results. They note, also, that vitamin D levels decrease and can be affected by many variables including  vitamin D‐rich food intake, sunlight exposure and skin colour.  These things, they say, require more careful study.

The study appeared in the journal Acta Neurologica Scandinavica​.

A diet rich in B vitamins is recommended to maintain optimal health of body and mind. Insufficient intake, on the other hand, has been linked with elevated levels of oxidative stress and neural inflammation, as indicated by abnormally high blood levels of the amino acid homocysteine.

At the same time, the effect of increased oxidative stress in the brain is not well studied, thus researchers at Swinburne University and Austin Hospital in Melbourne (backed by supplement manufacturers Blackmores) conducted a small randomised controlled trial to assess the direct impact of six months of high-dose B vitamin supplementation on brain health and levels of homocysteine and other biomarkers in the brain.

They recruited 32 healthy adults (12 male, 20 female) between the ages of 30 and 65, who were given either Blackmores’ Executive B Stress Formula tablets, or placebo that contained a small amount of glucose and riboflavin (2mg of B2).

The findings were published in the journal Nutrients.

Brain changes

Each participant took two tablets daily – one at breakfast and one at lunch – for six months. The researchers performed a series of blood tests, including tests for vitamins B6 and B12, folate and homocysteine levels at baseline and after the trial.

The team also used magnetic resonance spectroscopy to look at the posterior cingulate cortex (PCC, linked to memory and emotions) and dorsolateral prefrontal cortex (DLPFC, involved in as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning) in the study participants before and after supplementation.

What they found was that the supplemented group experienced an increase in blood plasma vitamin B6 and B12 levels, as well as a decrease in blood plasma homocysteine.

Additionally, the researchers observed significant relationships between vitamin B6 and N-acetylaspartate (NAA, the second-most concentrated molecule in the brain), creatine and choline, as well as between vitamin B12 and creatine.

They also found that within the supplemented group, NAA in the PCC increased, though not enough to be considered statistically significant.

There was, however, no change in the group’s folate levels. However the paper notes that many foods sold in Australia, such as bread and milk, are already fortified with folate which could explain why folate levels did not change with supplementation.

Beyond folate

While folate is usually credited with reducing homocysteine levels, this study found that that although vitamins B6 and B12, along with folate, usually worked together to maintain cardiovascular, neural and psychological health by regulating homocysteine, the results suggested that the higher levels of blood plasma vitamin B6 and B12 was responsible for lowering blood plasma homocysteine levels.

They concluded that since vitamin B6- and B12-dependent enzymes – cystathionine B-synthase and methionine synthase, respectively – drove homocysteine catalysis, supplementation with a high-dose vitamin B multivitamin could “promote the breakdown of homocysteine to a greater extent than folate​”.

Follow-up needed

This was a small study, and the researchers suggest its findings should be treated as “preliminary findings that warrant further investigation with a larger sample”​.

They stated that this was the first study to have assessed the efficacy of high-dose vitamin B multivitamin supplementation in regulating the relationship between blood and neural biomarkers of oxidative stress.

In conclusion, they wrote: “Increasing levels of blood high-dose B-group vitamins were also associated with increased neural metabolism. These findings suggest that high-dose B-group vitamin supplementation might be effective in reducing oxidative stress and inflammation through increasing oxidative metabolism, and may promote myelination, cellular metabolism, and energy storage.​

“Together, these findings highlight the importance of B-group vitamins in the maintenance of brain health in healthy adults, and may have important implications in the prevention and alleviation of disease and disability.”

Researchers from the University of Leuven in Belgium studied 935 randomly recruited Flemish people around the age of 40.

Analysing their vitamin K status, the researchers found a correlation between a participants’ levels of matrix Gla protein, or MGP, which helps keep arteries from clogging. Low levels of MGP can indicate a vitamin K deficiency.

“MGP is abundantly expressed in the eye, where it takes part in preserving the structural integrity of the trabecular meshwork, the sclera, and the retinal ganglion cells,”​they wrote. In other words, MGP supports healthy tissue, balances ocular pressure and circulation supports the transmission of visual information to the brain.

Considering that activation of MGP requires vitamin K, the researchers hypothesised that there could be a link between vitamin K intake and eye health.

Over the 11 year follow up, higher levels of MGP did indeed point to a much healthier microvascular structure in the eyes which in turn supports overall eye health.

Writing in the journal Scientific Reports​​​ they say the findings suggest that supplementing with vitamin K could help promote eye health as we age.

Since the study did not look at vitamin K supplementation directly, more study is needed in this area and also to see if these results can be repeated in larger and more diverse populations but initial results are encouraging.

Getting more in your diet

Vitamin K is a fat-soluble vitamin that comes in two main forms: phylloquinone, also known as phytonadione, (vitamin K1) which is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90% of the vitamin K in a typical Western diet;

Menaquinone (vitamin K2), makes up about 10% of Western vitamin K consumption, and can be produced in the gut by microflora.

Like vitamins C and E vitamin K is a ‘family’ and other types of menaquinones can also be found in the food we eat; MK-4 can be found in animal meat, MK-7, MK-8, and MK-9 are found in fermented food products like cheese, and natto is also a rich source of MK-7.

A diverse diet and a healthy gut can help ensure you get enough vitamin K.

A secondary analysis of the UK National Diet and Nutrition Survey, published in Frontiers in Nutrition, highlights a tendency to report micronutrients intakes collectively for adults, with broad age ranges being used. This means that certain sub-population groups such as younger adults are often overlooked.

The current analysis, which looked at these subpopulations, noted that improvements in dietary quality are needed in young adulthood and mid-life. To achieve this, they note, supplementation strategies could help young adults be where they should be at these ages – in their “nutritional prime.”

The analysis found sizeable deficiencies in several important nutrients. For magnesium in both men and women, 19% of young people in their twenties having intakes below the Lowest Recommended Nutrient Intake (LRNI). There were also considerable gender gaps in dietary selenium intakes, with 50% females and 26% of males having total intakes beneath the LRNI.

Furthermore, a quarter of women had both iron and potassium intakes below the LRNI, while among UK males, vitamin A and zinc shortfalls were apparent.

The researchers say that an adequate micronutrient profile for women is not only important for fertility but also to prepare the body for the extensive physiological demands should pregnancy occur. Selenium, for example, has been highlighted as a crucial nutrient for women seeking to become pregnant.

By increasing their risk of preeclampsia, mothers with low selenium levels may also be at increased risk for heart disease, stroke and high blood pressure later in life. The summary calls for higher levels of supplementation of high selenium yeast to combat heart health threats.

Male fertility at risk too

Zinc, of course, is a known antioxidant with research showing that fertile males tend to have higher seminal zinc levels than their infertile men. Zinc also helps to support immunity and avert age-related diseases.

Zinc shortfalls are somewhat surprising to see, the researchers add, especially among males, given that meat and meat products are one of the main providers of zinc. It is possible that younger men in their twenties are eating less meat which could have contributed to lower zinc intakes in this age group, the researchers note. This is an important finding and worthy of consideration in the context of public health given current trends toward plant-based diets, they explain.

In terms of the low vitamin A intake found in males, the researchers found that young men’s mean intakes of fruit and vegetables were slightly lower at 3.9 portions daily compared with 4.1 portions daily among women aged 19 to 64 years. It has also been found that fruit and vegetable variety tends to be lower in men, especially in instances where education and social class is lower.

Why are levels so low?
Adequate nutrition at this stage of life can also help to future-proof health against debilitating and chronic diseases that can occur in later life.

The researchers suggested that when it comes to women’s nutritional shortfalls, societal pressures around body image could be a factor. They cite a recent survey of 1,035 social media tweets typically used by young adults that found that 67% related to body image, eating disorders, fitness, food or dieting. This, in turn, could have wider ramifications impacting on dietary habits and micronutrient profiles of young women.

Emerging food trends and the avoidance of food groups could also be impacting on micronutrient intakes. For example, the consumption of eggs, milk, and dairy correlates strongly against female nutritional iodine status while veganism has also been found to impact on vitamin D, calcium and vitamin B12, iodine and selenium intakes. They further add that UK females having diets lower in red meat (less than 40 g daily) have reduced micronutrient intakes, especially zinc and vitamin D.

“It is imperative to continue raising awareness about the importance of healthy and balanced diets and adequate micronutrient intakes. The implications of ‘cutting back or cutting out’ certain food groups also need to be communicated, especially to younger generations who are strongly influenced by social media which is not subject to peer review or monitoring systems,” says author Dr. Emma Derbyshire, Public Health Nutritionist and an advisor to the Health & Food Supplements Information Service (HSIS).

A daily insurance policy
The current research found that females and young adults are at particular risk of micronutrient shortfalls. In an environment, where the public are being encouraged to reduce their energy intakes, it is important to ensure that younger people get the nutrient they need sand that multivitamin and mineral supplements could help.

Supplement, of course, are no substitute for a healthy diet, but as the nutrient content of our food declines and food fads become more prevalent, they may be an important insurance policy for health. For information on choosing the best supplements see our article What to look for in supplements.

The analysis by researchers at University of California San Diego School of Medicine, pooled data from two randomised clinical trials with 3,325 combined participants, plus a prospective study involving 1,713 participants, to examine the association between risk of female breast cancer and a broad range of serum 25-hydroxyvitamin D (or, 25(OH)D) concentrations, the main form of vitamin D in blood.

All women were age 55 or older. The average age was 63. Data were collected between 2002 and 2017. Participants were free of cancer at enrollment and were followed for a mean period of four years. Vitamin D levels in blood were measured during study visits.

Over the course of the combined studies, 77 new cases of breast cancer were diagnosed for an age-adjusted incidence rate of 512 cases per 100,000 person-years.

Official recommendations inadequate

Researchers identified the minimum healthy level of 25(OH)D in blood plasma to be 60 nanograms per millilitre, substantially higher than the 20 ng/ml recommended in 2010 by the Institute of Medicine, now the National Academy of Medicine, a health advisory group to the federal government.

Some groups, such as GrassrootsHealth an California-based nonprofit organisation that promotes vitamin D research and benefits, and which collaborated on this analysis, have advocated higher minimums for health blood serum levels of vitamin D, as much as 50 ng/ml, though the matter remains hotly debated.

“We found that participants with blood levels of 25(OH)D that were above 60 ng/ml had one-fifth the risk of breast cancer compared to those with less than 20 ng/ml,” said principal investigator and co-author Cedric F. Garland, DrPH, adjunct professor in the UC San Diego Department of Family Medicine and Public Health. Risk of cancer appeared to decline with greater levels of serum vitamin D.

A strong association

Even after adjusting for known risk factors for breast cancer such as age, body mass index, cigarette smoking and intake of calcium supplements, the benefits were still apparent, suggesting that increasing vitamin D blood levels substantially above 20 ng/ml could be important for the prevention of breast cancer.

According to Garland, who has previously studied connections between serum vitamin D levels and several types of cancer, said the study builds upon previous epidemiological research linking vitamin D deficiency to a higher risk of breast cancer.

“This study was limited to postmenopausal breast cancer. Further research is needed on whether high 25(OH)D levels might prevent premenopausal breast cancer,” Garland said. The population was also mainly white women so further research is needed on other ethnic groups.

“Nonetheless, this paper reports the strongest association yet between serum vitamin D and reduction in risk of breast cancer,” Garland said.

Results were published in the journal PLOS ONE.

Years of advocacy

Garland and others have advocated the health benefits of vitamin D for many years. In 1980, he and his late brother Frank C. Garland, also an epidemiologist, published an influential paper that posited vitamin D (produced by the body through exposure to sunshine) and calcium (which vitamin D helps the body absorb) together reduced the risk of colon cancer. The Garlands and colleagues subsequently found favourable associations of markers of vitamin D with breast, lung and bladder cancers, multiple myeloma and adult leukaemia.

The current recommended average daily amount of vitamin D3 is 400 IU for children up to one year; 600 IU for ages one to 70 years (including pregnant or breastfeeding women) and 800 IU for persons over age 70, according to the National Academy of Medicine.

To reach 25(OH)D levels of 60 ng/ml, said Garland, would generally require dietary supplements of 4,000 to 6,000 international units (IU) per day, less with the addition of moderate daily sun exposure wearing very minimal clothing (approximately 10-15 minutes per day outdoors at noon). He said the success of oral supplementation should be determined using a blood test, preferably during winter months.

Natural Health News — Two new studies have revealed the importance of vitamin D in both preventing, and lessening some of the inflammation caused by, diabetes.

In the first scientists from California and Seoul in South Korea collaborated to study a group 903 healthy older adults with no indications of either pre-diabetes or diabetes during clinic visits from 1997 to 1999, and then followed the participants through 2009. Vitamin D levels in blood were measured during these visits, along with fasting plasma glucose and oral glucose tolerance.

Over the course of time, there were 47 new cases of diabetes and 337 new cases of pre-diabetes, in which blood sugar levels are higher than normal but not yet high enough to be categorized as type-2 diabetes.

In this study, published in PLOS One, the researchers identified the minimum healthy level of 25-hydroxyvitamin D in blood plasma to be 30 nanograms (ng) per millilitre (ml). That’s 10 ng/ml above the generally recommended level – though increasingly nutritionists argue that higher levels, as much as 50 ng/ml would be a better benchmark.

“We found that participants with blood levels of 25-hydroxyvitamin D that were above 30 ng/ml had one-third of the risk of diabetes and those with levels above 50 ng/ml had one-fifth of the risk of developing diabetes,” said first author Sue K. Park, MD, in the Department of Preventive Medicine at Seoul National University College of Medicine in South Korea.

More is better

According to study co-author Cedric F. Garland, DrPH, adjunct professor in the UC San Diego School of Medicine Department of Family Medicine and Public Health, to reach 25-hydroxyvitamin D levels of 30 ng/ml, would require dietary supplements of 3,000 to 5,000 international units (IU) per day, less with the addition of moderate daily sun exposure with minimal clothing (approximately 10-15 minutes per day outdoors at noon).

The current recommended average daily amount of vitamin D is 400 IU for children up to 1 year; 600 IU for ages 1 to 70 years (less for pregnant or breastfeeding women) and 800 IU for those over 70.  Higher daily amounts of vitamin D are generally considered safe, but as with everything there are limits. Very high blood serum levels exceeding 125 ng/ml have been linked to adverse side effects, such as nausea, constipation, weight loss, heart rhythm problems and kidney damage. This is why many doctors recommend having your blood levels of vitamin D tested before considering high dose supplements.

Reducing inflammation

In a second study – an analysis of 20 high quality trials – Australian researchers from Monash University, Melbourne found that supplemental vitamin D could help reduce inflammation in people with diabetes.

The study looked at vitamin D status and levels of inflammatory biomarkers – substances produced by the body when inflammation is present. A well-known example of this is C-reactive protein (CRP) produced by the liver in response to inflammation, infection and tissue injury. In this study, published in Nutrition Reviews, vitamin D supplementation CRP, as well as other important biomarkers such as tumour necrosis factor alpha and erythrocyte sedimentation rate. It also helped increase levels of leptin a hormone that helps to regulate energy balance by inhibiting hunger.

Chronic low-grade inflammation is widely known to be present in, and precedes, the development of type-2 diabetes and raises the risk of a whole range of diabetes complications such as damage to blood vessels.

“This is the first ever systematic review and meta-analysis on this topic in patients with type-2 diabetes,” commented senior researcher Associate Professor Barbora de Courten. “If vitamin D supplementation can improve inflammation, as shown here, there may be important benefits for patients with type-2 diabetes, given that elevated inflammatory markers promote insulin resistance, dyslipidaemia [an abnormal amount of triglycerides, cholesterol and/or fat phospholipids in the blood] and atherosclerosis.”

Building the case for supplementation

The majority of the trials analysed used vitamin D3 in doses of 200-6000 IU daily. A handful looked at very large doses e.g. 50 000-60 000 IU weekly or bi-weekly or a single bolus dose of 300 000 IU.

The researchers say it is too soon to make the blanket recommendation that everyone with diabetes should be given vitamin D supplements and recommend assessing need the need for and level of supplementation on a case by case basis.

However taken together along with other studies that show that low vitamin D status is linked to metabolic syndrome and poorer mental health in women with type-2 diabetes there is an increasingly strong case for vitamin D supplementation where diabetes is a risk.