295. Vitamin D: Are We Getting Enough?

Rheumatoid arthritis

A recent paper reports on research conducted at the University of Birmingham has discovered that maintaining sufficient vitamin D levels may help to prevent the onset of inflammatory diseases like rheumatoid arthritis (1). The scientific paper is available here (2). It was also found that although Vitamin D can help to prevent the onset of inflammation, it is less effective once inflammatory disease is established because diseases such as rheumatoid arthritis leads to vitamin D insensitivity.

Because Vitamin D is a potent modulator of the immune system, it can suppress inflammation in autoimmune diseases such as rheumatoid arthritis. Patients with rheumatoid arthritis are frequently vitamin D deficient and may receive vitamin D supplementation. When clinicians are using Vitamin D to treat rheumatoid arthritis, they may need to prescribe much higher doses than currently employed.

This is just one more example, which indicates that relatively high doses may be needed to ensure that Vitamin D can function effectively.

The official recommendations

In the UK, the Scientific Advisory Committee on Nutrition (SACN) produced a report entitled “Vitamin D and Health” that was released in July 2016 (3). Prior to this report the recommendations were based on the prevention of rickets in children and osteomalacia in adults. A dietary intake of vitamin D was not considered necessary for individuals with adequate exposure to sunlight. For those considered at risk of deficiency, which included pregnant and breast-feeding women, adults aged 65y and above, those with limited exposure to sunlight (e.g., confined indoors or wearing concealing clothing) and people of Asian ethnic origin it was recommended the daily intake should be 400 IU/10 µg per day.

Rationale for the recommendations

An estimation of Vitamin D status can be derived from measuring the concentration of 25(OH)D in the blood serum. The SACN report noted that in the majority of studies this value was < 25 nmol/L in children with rickets and that most children in the general population with a serum 25(OH)D concentration < 25 nmol/L will not develop rickets. For osteomalacia, there was some indication that there was an increased risk when the serum 25(OH)D concentration < 20 nmol/L. There a suggestion that there was an association between the serum 25(OH)D content of the pregnant mother and the bone health of the foetus/newborn but

“the physiological significance of this is not known.”

There were also possible benefits in those >50 years old with respect to bone health and susceptibility to fractures. In those <50 years old, supplementation with Vitamin D may improve muscle strength and function if the mean serum 25(OH)D concentration < 30 nmol/L.

The group considered the evidence on the relationship between vitamin D and a range of non-musculoskeletal health outcomes. These included reproductive health (on maternal & newborn outcomes), cancers, CVD, hypertension, all-cause mortality, immune modulation (asthma, atopic disorders, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis), infectious diseases (TB, acute respiratory tract infections), neuropsychological functioning (cognitive function, dementia, autism, depression, schizophrenia), age-related macular degeneration and oral health.

Regrettably this was dismissed as follows:

“Evidence for the proposed benefits of vitamin D on non-musculoskeletal health outcomes is drawn mainly from observational studies so findings might be due to reverse causality (i.e., low 25(OH)D concentration is a consequence of the illness rather than the cause) or confounding by other factors associated with a specific health outcome.  Findings from RCTs of vitamin D supplementation and nonmusculoskeletal health outcomes are inconsistent.  Overall, there was insufficient evidence on vitamin D and non-musculoskeletal health outcomes to inform the setting of DRVs for vitamin D.”

As a consequence, the basis for making the dietary recommendations was restricted to evidence relating to rickets, osteomalacia, falls and muscle strength and function.

Getting up to date

In my view, SACN has failed miserably to do an objective evaluation of the totality of evidence on the role of Vitamin D in the maintenance of good health. In fact there is an accumulation of information, which demonstrates the importance of this vitamin. Much of this has been initiated and collated by Grassroots Health (GRH) in the USA, which is the brainchild of Carole Baggerley who recovered from cancer partly by the consumption of high levels of Vitamin D.

Here is a selection of the information, which I have accessed from the Grassroots Health website (4). It is highly significant that much of this was available long before the publication of the SACN report.

Preterm births

Based on an analysis of information from 509 pregnant women participating in Vitamin D supplementation, there was a clear association between 25(OH)D serum concentration within six weeks of delivery and preterm birth (5). In those women with a 25(OH)D serum concentration of ?100nmol/L there was a significantly decreased the risk of preterm birth compared to those with values ?50 nmol/L. Although women with 25(OH)D concentrations between 50 and 100 nmol/L also had a decreased risk of preterm birth, this was less of a decrease (41% vs. 59% in women with 25(OH)D ?100 nmol/L) and it was not statistically significant. These findings support the premise that 25(OH)D concentrations of 100 nmol/L and above are needed to significantly reduce the risk of preterm birth.

Cancer

Data from 2304 women who participated in 2 different studies were analysed to determine the relationship between the serum 25(OH)D content and the incidence of cancer(6). Over the period of the trials, there were 58 cases of cancer (43% were diagnosed as breast cancer. It was found that women with 25(OH)D concentrations ?100 nmol/L had a significantly lower risk of cancer (~70%) compared to women with concentrations <50 nmol/L. The paper also noted that there had been several other studies, which produced similar results. One of these was a hospital-based case control study that women with serum concentrations of >150 nmol/L had an 83% reduction in breast cancer risk compared to women with concentrations <50 nmol/L (7).

In a Norwegian study of 658 patients with cancers of the breast (n = 251), colon (n = 52), lung (n = 210), and lymphoma (n = 145), it was found that 396 died during follow-up, of whom 343 (86%) died from cancer (8). The death rates from cancer and the serum 25(OH)D levels are shown in Table 1. This shows very clearly that those win the highest quartile had death rates that were one third of those in the lowest quartile. The authors considered it unlikely that results could be due to reverse causality.

Table 1. Relationship between serum 25(OH)D levels and risks of death from cancer in patients with cancer of breast, colon, prostate, or lymphoma.

Type 2 Diabetes (T2D)

This study is especially interested because it compares two different cohorts. One is from the National Health and Nutrition Examination Survey (NHANES) and is designed to be representative of the US population aged >20 years and had no history of T2D in the previous 12 months (9). There were 4078 participants in this cohort. The other was of people who had been participating in a GRH study and were encouraged to take Vitamin D supplements. Data was used from 4933 participants selected to match those in the NHANES cohort.

In this group, 30% reported taking Vitamin D supplements with a median daily intake of 400 IU. However in the GRH group, 77% of participants reported supplements. The median daily intake of Vitamin D was 2400 IU. The 25(OH)D serum concentration was 103 nmol/L in the GRH cohort but in the NHANES cohort it was only 77 nmol/L.

There were 38 individuals who developed T2D in the NHANES cohort but only 10 in the GRH cohort. When adjustments were made for differences in age, gender, race, smoking status, and BMI, the expected number of cases was 25 in the NHANES group compared to the 10 observed GRH cases. There were big differences within the NHANES cohort: those with serum 25(OH)D levels <63 nmol/L had almost 5 times the odds of developing diabetes compared to those with serum 25(OH)D levels >63 nmol/L.

The significance of this study is that the fundamental difference between the two cohorts is that the GRH group had been actively taking steps to increase the level Vitamin D within their bodies and this indicates that one benefit of doing so is a reduction in the incidence of diabetes. The variation in the incidence of T2D in the NHANES group with serum 25(OH)D levels is entirely consistent with this conclusion. The key difference between the two groups is that the GRH one was composed of individuals actively boosting their Vitamin D levels. This strongly suggests that it is beneficial to do so and that the low levels associated with the higher incidence of T2D is not a consequence of the disease.

The paper also refers to other studies that obtained essentially similar results, including the following:

• There was a strong inverse association between serum 25(OH)D concentration and incidence of T2D (10). Those with serum 25(OH)D >80 nmol/L had a 41% lower risk of diabetes compared with those with <50 nmol/ L. This was based on a meta-analysis of 11 prospective studies involving a total of 3,612 cases and 55,713 non-case participants.
• A study presented at the 2014 Endocrine Society Meeting found a 58% reduction in the progression from prediabetes to diabetes in a group treated with calcium and 60,000 IU/week of vitamin D for eight weeks and then monthly compared to a group given only calcium supplements (11).

Conclusion

It is abundantly clear that the SACN report does not address the issue properly. It simply does not make sense to dismiss non-musculoskeletal conditions. It is obvious from the evidence cited here that there is a link between the level of Vitamin D in the body and the incidence of various diseases. It is especially noteworthy that the difference between the two groups in the T2D study was the Vitamin D supplementation in the GRH cohort. The basis of the SACN recommendation of a serum concentration of 20 nmol/L for 25(OH)D is simply far too low. The work of the GRH suggests that it should be very much higher. There are convincing reasons that the SACN recommendation of 400IU/day should be increased by a factor of at least 10. As a consequence, there must be large numbers of people in the UK who assume quite wrongly that they are meeting the requirements for Vitamin D when there is every possibility that they would benefit from a much higher daily intake.

References

1. https://www.birmingham.ac.uk/news/latest/2017/11/vitamin-D-arthritis-inflammation-research.aspx
2. L E Jeffrey et al (2017). https://ac.els-cdn.com/S0896841117304201/1-s2.0-S0896841117304201-main.pdf?_tid=488acb02-cea7-11e7-a2fe-00000aab0f6b&acdnat=1511260533_972b25f684bc69de5eb8086e212aeb6d
3. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/537616/SACN_Vitamin_D_and_Health_report.pdf
4. https://grassrootshealth.net/research/
5. C L Wagner et al (2016). https://ac.els-cdn.com/S0960076015301242/1-s2.0-S0960076015301242-main.pdf?_tid=8bcbbce8-cf9a-11e7-a5ed-00000aab0f02&acdnat=1511365013_3c8c52d35b9d568add6c1ed87b2b33d0
6. S L Mc Donnell et al (2016). https://grassrootshealth.net/document/cancer-risk/
7. L C Lowe et al (2005). https://www.ncbi.nlm.nih.gov/pubmed/15911240
8. S Tretli et al (2012). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261400/
9. S L Mc Donnell et al (2016). Journal of Steroid Biochemistry & Molecular Biology 155 pp 239–244
10. N G Forouhi et al (2012). https://link.springer.com/content/pdf/10.1007%2Fs00125-012-2544-y.pdf
11. D Dutta et al (2014). Presented at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014, Chicago, USA