Tuesday, October 15, 2013

Milky mismatch: Vitamin D levels in human milk and legacies of past behaviors

I have been thinking a lot about Vitamin D lately. Wrapping up field work at high altitude, coupled with my love of outdoor running means I have spent a near fortune on sunscreen as of late. We also had a baby with early stage jaundice in our study. His parents were understandably concerned, and treated the jaundice with lots of breastfeeding (see ABM treatment protocol here: http://www.ncbi.nlm.nih.gov/pubmed/20387269 ) and sunshine. In fact, he was put in his bassinet outside under a mosquito net every time the monsoon eased up. 

It was a stark contrast to my skin cancer concerns, where twice daily I coated myself in any number of sunblocking chemicals. Reading the labels, the products were safe for infants older than six months . . . below that, ask a physician.  The general recommendation is to keep infants out of the sun and reduce the risk of sunburn and UV exposure. The source of Vitamin D for infants is breast milk (or formula). The Vitamin D in human milk comes from maternal synthesis. 

Vitamin D synthesis by the body requires a UV wavelength of 290-300nm; this is only available when the UV index is above 3. The UV rays absorbed by the skin convert the prohormone 7-dehydrocholesterol into cholecalciferol. This travels via the bloodstream to the liver, where it is metabolized into 25-hydroxyvitamin D. Synthesis is then almost done: the hydroxyvitamin D travels to the kidneys, where it is converted to the metabolically active dihydroxyvitamin D (Vitamin D). Vitamin D aids the body in calcium absorption, and appears to play a major role in regulating insulin, calcium, and phosphorus levels in the body. 

And as most people know, skin color is directly associated with UV absorption and Vitamin D production. Skin pigmentation is determined largely by the amount of melanin – more melanin = darker skin. More melanin results in increased UV deflection which means decreased risk of harmful UV rays being absorbed (and a decreased risk of skin cancer) but increased risk of Vitamin D deficiency at higher latitudes. UV light, and Vitamin D synthesis, is thought to have played a major role in the evolution of skin color, with darker skin colors found around the equator, where there is plenty of sunlight and opportunity to make Vitamin D and UV damage is a bigger risk. Lighter skin colors are found at higher latitudes as the amount of daily and direct sunlight decreases: less melanin increases UV absorption (Antoniou et al., 2009). This may be beneficial in preventing Vitamin D deficiency, including rickets. Some populations, like Inuit, may also supplement through dietary sources of Vitamin D (whale liver anyone?). Sunscreen is incredibly effective at blocking UV rays: a SPF of 8 blocks 95% of the UV; SPF 15 99%.  Other factors influencing vitamin D levels are body size, specifically the amount of body fat individuals may have. Vitamin D is fat soluble. Extra Vitamin D is stored in fat cells, and may not be accessible unless the fat is metabolized.

So how do you get enough Vitamin D without exposure to too much sun? The good news is for most of us, especially during the summer, we get enough in short bursts that our Vitamin D levels are pretty good. On a sunny day, walking to and from your parking space at work or the grocery store or similar is probably enough. The best estimates are 5-30 minutes of exposure, from 10am to 3pm, 2-3 times a week are sufficient to meet most individual’s Vitamin D needs, provided the face, arms, and neck are uncovered. Darker skin tones will need more exposure. There is a handy online calculator where you can put in your data (including latitude) and it will generate an estimate. The human body is remarkably efficient at making Vitamin D: 10,000-20,000 IU can be synthesized in 30 minutes. 

Figure 1: Capacity for Vitamin D synthesis in light skinned (low melanin) individuals by latitude during winter. Image is from: Tavera-Mendoza and White, Scientific American, Nov. 2007, by way of http://www.medicine.mcgill.ca/physio/whitelab/research.htm

However, nursing mothers will need more Vitamin D, as will individuals with limited sun exposure, heavy use of sunscreen, darker skin colors, living at higher latitudes (especially during the winter), higher body fat, and vegetarians. Most milk sold in the United States is fortified with Vitamin D, as are many breakfast foods. Between sunshine and food fortification, most women are likely meeting their own needs. 

But the real question you came for is about babies. Should breastfed babies, especially exclusively breastfed babies, receive Vitamin D supplementation? Or is supplementing mothers with extra Vitamin D an alternative treatment strategy?

Vitamin D deficiency is probably fairly common: Choi et al., (2013) reported a prevalence of 48.7% in Korean infants, with breastfed infants more likely to be vitamin D deficient than formula fed infants, likely reflecting fortification of infant formula with supplemental vitamin D. Similarly high rates of Vitamin D deficiency were reported in Turkish infants (Halicioglu et al., 2012). In the United States, the incidence rate is approximately 25-40% for unsupplemented exclusively breastfed infant. Infants need approximately 400 IU of Vitamin D per day, and based on current estimates for human milk, infants are unlikely to get sufficient Vitamin D from human milk alone. 

 “Despite the association between sunlight exposure and human milk vitamin D concentration, there are no reports of the effect of long-term sunlight exposure of the mother on her milk vitamin D concentration.”  Dawodu A, Tsang RC. 2012 Adv Nutr 3: 353-361. 

However, we do have some evidence: a few studies do exist looking at the relationship between maternal and milk Vitamin D levels, often called antirachitic activity, as the measure includes both the biological activity of Vitamin D and its metabolites. Most of these studies are supplementation studies – providing mothers with additional vitamin D, rather than relying on maternal synthesis. 

One of the first major supplementation studies is that of Hollis and Wagner (2004). Eighteen mothers at one month postpartum were enrolled into one of two treatment groups: 1600 IU D2 + 400 IU D3 or 3600 IU D2 + 400 IU D3. Mothers continued in the study for 3 months when milk antirachitic activity was tested. Both groups showed an increase in milk antirachitic activity: group one had a milk mean of 34.2 IU/L and group 2 a milk mean of 94.2 IU/L. However, neither increase was sufficient to meet infant metabolic requirements. 

This was followed by a study by Saadi et al., (2009).  Working with a sample of Middle Eastern women, Saadi et al., used two treatment groups: one receiving 2000 IU/day of Vitamin D and the other receiving 60,000 IU/month. Mothers reported seven minutes per week of sun exposure, low dietary intakes of Vitamin D rich fish, and had undetectable antirachitic activity in their milk prior to entering the study. Supplementation increased milk antirachitic levels in these women to 50 IU/L (10-63 IU/L), within the range of US women relying only on incidental sun exposure for synthesis. The 50 IU/L levels are considered low, and well below the recommended intake for infants.  

In a large meta-analaysis of available studies on Vitamin D supplementation of mothers as a way of managing infant Vitamin D needs, Dawodu and Tsang (2012) conclude that based on the evidence currently available, it is unlikely that maternal supplementation could increase the antirachitic activity of milk enough to meet infant requirements. 

While human milk is almost always the ideal first food for human infants, that does not mean it meets 100% of needs 100% of the time. Specifically, given that human babies likely had plenty of sun exposure for the majority of human evolutionary history (including as recently as our grandparents and still in many parts of the world) there would have been minimal selective pressure on increasing Vitamin D transfer into milk. Babies, especially in tropical climates and during certain seasons of the year, may have received plenty of sunlight, certainly enough for individual synthesis of Vitamin D. Long term exposure to damaging UVs would have a byproduct, but probably not as important as synthesizing enough Vitamin D to prevent rickets, seizures, and other factors associated with low Vitamin D synthesis. Mothers also, likely had plenty of exposure to sunlight, probably had much higher levels of circulating Vitamin D, and greater amounts of it in milk.  Vitamin D requirements were probably meet by the mutual sun exposure of mothers and infants, and Vitamin D requirements during infancy and childhood may have contributed to selection against melanin at high latitudes and a reduction in skin pigmentation to maximize synthesis.

Figure 1: A mother and baby from Nurbi, Nepal. Babies are typically worn on the back or carried in baskets and receive plenty of daily sun exposure. Photo: Geoff Childs, used with permission.

In evolutionary medicine, we use the term mismatch to describe situations where current behaviors have changed dramatically from similar behaviors throughout human evolutionary history. That is not to suggest some sort of fictionalized single environment that humans are perfectly adapted to, but a general observation about how we likely cared for babies during most of our evolutionary history and even today in many parts of the world, including my field sites in the Philippines and the Himalayas.  Babies and mothers were outside in the sun, and had plenty of opportunities for Vitamin D synthesis . . . and also exposure to harmful UV rates and sunburn. Further, with the continued degradation of the ozone layer, the potential for sunburn and skin damage is high. And Vitamin D supplementation of moms and babies is great solution. 

Mismatch does not have to mean pathology, and this is one of those great situations where understanding why something isn’t present in milk can help us better understand current clinical practice.

Antoniou C, Lademann J, Schanzer S, Richter H, Sterry W, Zastrow L, Koch S. 2009. Do different ethnic groups need different sun protection? Skin Res Technol. 15(3):323-9. doi: 10.1111/j.1600-0846.2009.00366.x.

Choi YJ, Kim MK, Jeong SJ. 2013. Vitamin D deficiency in infants aged 1 to 6 months. Korean J Pediatr. 56(5):205-10. doi: 10.3345/kjp.2013.56.5.205. 

Dawodu A, Tsang RC. 2012. Maternal vitamin D status: effect on milk vitamin D content and vitamin D status of breastfeeding infants. Adv Nutr. May 1;3(3):353-61. doi: 10.3945/an.111.000950.

Halicioglu O, Aksit S, Koc F, Akman SA, Albudak E, Yaprak I, Coker I, Colak A, Ozturk C, Gulec ES. 2012. Vitamin D deficiency in pregnant women and their neonates in spring time in western Turkey. Paediatr Perinat Epidemiol. 26(1):53-60. doi: 10.1111/j.1365-3016.2011.01238.x.

Hollis BW, Wagner CL. 2004. Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant. Am J Clin Nutr. 80(6 Suppl):1752S-8S.

Saadi HF, Dawodu A, Afandi B, Zayed R, Benedict S, Nagelkerke N, Hollis BW. 2009. Effect of combined maternal and infant vitamin D supplementation on vitamin D status of exclusively breastfed infants. Matern Child Nutr. 5(1):25-32. doi: 10.1111/j.1740-8709.2008.00145.x.

Wagner CL, Hulsey TC, Fanning D, Ebeling M, Hollis BW. 2006. High-dose vitamin D3 supplementation in a cohort of breastfeeding mothers and their infants: a 6-month follow-up pilot study. Breastfeed Med. 1(2):59-70.