'The Widespread Effects of Magnesium & Vitamin D: Natural Therapies ’'
sponsored by Rio Health

Please note, this is a transcript of the questions received and have been reproduced verbatim in relation to any grammatical errors.

Which type and what dosage of magnesium is best to counteract losses from PPIs? Also, when to take for best results?

Excellent question.

As explained in the webinar, proton pump inhibitors (PPIs) can cause significant magnesium deficit even after a few weeks of use. This is because PPIs affect intestinal absorption, reducing the ability to release magnesium from food. Long-term use of PPIs may therefore induce magnesium deficiency.

During research for the webinar, I read that supplementing with magnesium won’t correct the deficiency. However, I have also seen mention that ‘the defect in magnesium absorption is clearly reversible…. Hypomagnesaemia improved upon withdrawal of PPIs….it is possible that intermittent use of PPIs might not cause hypomagnesaemia.’[i] The authors report that high-dose oral magnesium supplements (two to three times the typical daily intake) provided partial resolution of hypomagnesaemia. They further suggest that the passive magnesium transport was intact and the PPI likely induced defective function of the active transport mechanism.

Note that the above-mentioned study reported that ‘the problem (of severe magnesium depletion) only became evident after several years…..The long delay in the development of severe hypomagnesaemia (9 and 5 years, respectively) presumably reflects the time it took for magnesium stores to become depleted’ and ‘in short-term studies, PPIs have no detectable effect on magnesium absorption.’ 

PPIs, for example, omeprazole, with prolonged use, reduces absorption of magnesium and vitamin B12.  PPIs also increase the risk of intestinal infection (e.g. Clostridium difficile).  Hypochlorhydria caused by chronic use of PPIs can also lead to respiratory and urinary tract infections and may associate with gastric cancer. Practitioners may wish to suggest to clients who are using PPIs long-term to discuss alternatives with the prescribing practitioner.

For clients taking PPIs (whether short-term or long-term) I recommend using Liposomal Magnesium (by epigenar®).  Liposomal delivery bypasses the digestive system. Nutrients that are liposomally-delivered readily enter the blood stream and directly absorb through cell membranes. Liposomal magnesium delivers directly to the cells. This is because liposomes are made of the same material as cell membranes thus making access through cell membranes easy.  Note that those on PPIs may also wish to supplement vitamin B12; Liposomal B12 (by epigenar®) is also available.

Magnesium supplements can be taken any time of day; if taking to aid sleep, some suggest taking before bedtime.  Liposomal supplements can be with or without food so at any time of the day.

How much sun exposure is needed by dark-skinned individuals (time wise)?

Another excellent question. 

Dark-skinned people need higher amounts of vitamin D because the higher melanin content of darker skin prevents UVB light entering the skin for production of vitamin D.  This is why the latest government advice is that dark-skinned individuals should supplement daily throughout the year.  The higher melanin content functions like a sunscreen and reduces the ability to make vitamin D by up to 99% which means dark-skinned individuals may need three to six times longer sun exposure to make the same amount of vitamin D that a person with lighter skin tones might need. 

According to a 2002 study[ii] that compared the most lightly pigmented (European, Chinese and Mexican) skin types with the most darkly pigmented (African and Indian) skin types, variation in skin pigmentation is strongly influenced by both the amount and the composition (or colour) of the melanin in the epidermis, with variation in melanosome size also likely having a significant role.   

 ‘The most lightly pigmented (European, Chinese and Mexican) skin types have approximately half as much epidermal melanin as the most darkly pigmented (African and Indian) skin types.  However, the composition of melanin in these lighter skin types is comparatively more enriched with lightly coloured, alki-soluble melanin components (up to three-fold). Regardless of ethnicity, epidermal melanin content is significantly greater in chronically photoexposed skin than it is in corresponding photoprotected skin (up to two-fold). However, by comparison there is only a modest enrichment of lightly coloured, alkali soluble melanin components in photoprotected skin (up to 1.3-fold). Analysis of melanosomes extracted from the epidermis in these subjects indicates that the proportion of spheroidal melanosomes is low in all skin types examined (<10%). This suggests that in human skin, pheomelanin is a very minor component of epidermal melanin, even in the lightest (European) skin types. Analysis of melanosome size revealed a significant and progressive variation in size with ethnicity: African skin having the largest melanosomes followed in turn by Indian, Mexican, Chinese and European.’

The melanin content helps to protect those with dark skin from potentially harmful overexposure to strong sunlight. The melanin content and other structural differences in the skin of some ethnic populations means that their skin is also protected from some of the visible signs of photoaging.

A 2016 discussion of the ageing differences re skin colour[iii] states that the decreased epidermal melanin component predisposes Caucasians to develop earlier signs of photoaging than other populations. And mentions a study that found having black skin is similar to wearing SPF 13.4 sunscreen!

‘Melanin is the major determinant of colour in the skin, and the concentration of epidermal melanin in melanosomes is double in darker skin types compared to lightly pigmented skin types. In addition, melanosome degradation within the keratinocyte is slower in darkly pigmented skin. Overall, darker skin has singly dispersed, large melanosomes that contain more melanin compared with the smaller, aggregated, less melanin-containing melanosomes that occur in lighter persons. The melanin content and melanosomal dispersion pattern is thought to confer protection from accelerated aging induced by ultraviolet (UV) radiation. In fact, Kaidbey et al[iv] demonstrated that black epidermis, on average, provided a SPF of 13.4.’

What is an excessive level of serum vitamin D, and what are the effects?

And, another great question. 

We hear a lot about vitamin D deficiency but less about vitamin D toxicity. Whilst there is some consensus on what equates to a deficient level, opinion as to sufficient and optimal levels vary.  In terms of what constitutes an excessive level of serum vitamin D, according to nih.gov documents, levels above 125 nmol/L (50ng/mL) are too high and might cause health problems. And it is generally accepted that serum levels of 375 nmol/L (150ng/mL) are considered to pose a significant risk of vitamin D toxicity.

Clinical symptoms of vitamin D toxicity include: confusion, apathy, recurrent abdominal pain, recurrent vomiting, polyuria (frequent urination), polydipsia (excessive thirst) and dehydration.  The clinical manifestation of vitamin D excess is severe hypercalcemia (high calcium in blood).  Excess blood calcium can weaken bones, create kidney stones,  and interfere with how the heart and brain work.  

Please note that vitamin D toxicity is rare, but it is serious. From my understanding, only excessive supplementation of vitamin D, malfunctions of the vitamin D metabolic pathway, or the existence of a disease that produces active vitamin D metabolite locally can cause vitamin D toxicity.

 As mentioned in the webinar (please read the quote on slide 52), the IOM (Institute of Medicine) have established an upper limit of 4000 iu for chronic intake of vitamin D. [Note that this is based on >50 nmol/L (>20ng/mL) equating to sufficiency and >125 nmol/L (>50ng/L) equating to reason for concern—although the Endocrine Society consider >75 nmol/L (>30ng/mL) equates to sufficiency].  According to a 2018 study,[v] potential chronic toxicity would result from administration of doses above 4000iu/day for extended periods (possibly for years).

 Whilst in situations where a client has very low levels of vitamin D, a higher daily intake might be recommended for a short period of time, serum vitamin D needs to be closely monitored (via testing), especially if either deficiency or excess is suspected.  Indeed, with many more members of the public interested in ensuring sufficient vitamin D level, it is important to ensure all clients obtain sufficient vitamin D supplementation but are not taking more than they require—especially if they are taking daily year-round supplementation of vitamin D for extended periods.

What is more difficult to determine is the target concentration of vitamin D.  There is much controversy about what serum level is sufficient and that level may differ from what is optimal.

The SACN look at advice to maintain a concentration of 25 nmol/L during times when UVB sunshine exposure is low. But for some (likely, most) individuals this amount may not be sufficient to maintain good health. Indeed, some sources would state that under 30 nmol/L is an indication of insufficiency. And, it is thought that some people need 100 nmol/L for optimum health.

Levels of 50 nmol/L (20ng/nL) or more is considered sufficient by some. The Endocrine Society consider serum 25(OH)D concentration of more than 75 nmol/L (30ng/mL) is necessary to maximize the effect of vitamin D on calcium, bone and muscle metabolism. 

At least 75 nmol/L is recommended by the Endocrine Society for pregnant women to avoid deficiency that might result in unfavourable health outcomes for both mother and infant. And, in terms of child development, less than 30 nmol/L predicted a worse performance in cognitive and language skills. 

Studies also show that vitamin D deficiencies (<50 nmol/L) increased the risk of developing Alzheimer’s disease and dementia. 

And 75-100 nmol/L is considered optimal for colorectal cancer risk reduction.

The overall consensus seems to be that whilst serum levels below 30 nmol/L are too low (and may weaken bones and otherwise negatively impact health), levels of 50 nmol/L (20ng/mL) or above are ‘adequate’ for most people for bone and overall health. And, levels above 125 nmol/L (50ng/mL) might be too high and may result in health problems.

A 2017 study[vi] that looked to determine an optimal serum vitamin D level in a middle-aged and elderly population residing in Shanghai, China, concluded that the optimal serum vitamin D level for the whole population was 55 nmol/L.  Males were determined likely to need more vitamin D than females to maintain normal bone mineral density and metabolic state. The authors also discuss that controversy persists regarding a standard cut-off point because a single cut-off point may not be suitable for all populations (for example, young/old, men/women). They also point out that too-high a cut-off point may lead to some individuals using aggressive treatment of vitamin D supplementation with potential risk for vitamin D intoxication.

As practitioners, we need to enquire about the vitamin D status of our clients. Many GPs now more commonly test for vitamin D status.  Testing can determine if there is concern over insufficiency or excess.  Many (perhaps most) clients will need supplementation year-round and not just during the dark winter days.

Remember to supplement alongside vitamin K2 and magnesium.

References

[i] Cundy T, Dissanayake A (2008) Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrin 69(2):338-341.

[ii] Alaluf S, Atkins D, Barrett K, Blount M, Carter N, Heath A (2002) Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin. Pigment Cell Res 15(2):112-118.

[iii] Vashi NA, Buainanin de Castro Maymone M, Kundu RV (2016) Aging Differences in Ethnic Skin. Journal of Clinical Aesthetic Dermatology 9(1):31-38.

[iv] Kaidbey KH, Agin PP, Sayre RM, Kligman AM (1979) Photoprotection by melanin—a comparison of black and

Caucasian skin. J Am Acad Dermatol 1(3):249–260.

[v] Marcinowska-Suchowierska E, Kupisz-Urbanska M, Lukaszkiewica J, Pludowski P, Jones G (2018) Vitamin D Toxicity—A Clinical Perspective. Front. Endocrinol. 9:550. doi: 10.3389/fendo.2018.00550

[vi] Aleteng Q, Zhao L, Lin H, Xia M, Ma H, Gao J, Pan B, Gao X (2017) Optimal Vitamin D Status in a Middle-Aged and Elderly Population Residing in Shanghai, China. Medical Science Monitor 23:6001-6011.