Vitamin D - Separating Fact from Fiction

Douglas S. Kalman PhD RD For: https://www.caliscc.org/events/events/may-2015-meeting.html • Miami Research Associates May 26, 2015 Society of Cosmetic Chemists – California Chapter • Florida International University Location: Duke’s, Malibu, CA.

Vitamin D: Wonder Pill or Overkill?

Wouldn’t it be great if one vitamin could build stronger bones and protect against diabetes, multiple sclerosis, cancer, heart disease, and depression? Or even help you lose weight? Researchers have high hopes for vitamin D -- which comes from our skin's reaction to sunlight, a few foods, and supplements. Let us review the latest science, the facts in the slides ahead … and see who's at risk for a "D" deficiency.

Vitamin D: From the Sun to You

How Much Sun?

Most people get some vitamin D from sunlight.

Phytoplankton and zooplankton have existed >500mm years – produces Vitamin D when exposed to sunlight. Spongebob and Patrick have always been tan.

UVB rays at 290 – 315 nm are absorbed by 7-dehydrocholesterol in the skin and converted into previtamin D3.

Latitude above 33.75 degrees and or altitude (>27N) affects vitamin D synthesis (169 – 1400m)

At 3500m, previtamin D3 formation is enhanced by as much as 4-fold.

It is estimated that sun exposure in a bathing suit for 15-20 minutes (1 minimal erythemal dose) = an oral D dose of 10,000 – 25,000 IU of D2. 1MED = minimal time to get a sunburn.

The sun and sunscreen

Melanin acts as a natural sunscreen when it absorbs UVB, diminishes production of D3 in the skin.

Sunscreen with a sun protective factor of 8 (SPF 8) absorbs 92-95% of UVB rays, reduces D3 production by 5-8%. If using 1-ounce, may reduce Vit D3 production by up to 95%.

SPF 15, if used on 1-ounce or more, may reduce Vit D3 production in the skin by up to 99% as it reduces UVB radiation also by ~99%.

African-Americans with very dark skin have a SPF of 15, and their ability to make D3 in the skin is reduced by up to 99%.

Aging, sunscreen and vitamin D

Aging reduces skin levels of pre vitamin D3 - a 70 y.o. has ~25% of pre D3 and 75% reduced capacity to make D3 in the skin as compared to a young adult.

SPF 17 (Australia) prevented rise in blood 1,25dihydroxyvitaminD3 as compared to placebo by a factor of 10, however levels of 25, hydroxyvitamin D3 unaffected. Blood levels for both markers maintained within reference range over the summer test period.

1,25-dihydroxy vitamin D is the most potent vitamin D metabolite, however, levels of the 25-OH forms of vitamin D more accurately reflect the body's vitamin D stores.

Thus, test 25 hydroxyvitamin D3 to assess vitamin D status.

Boney D or Sunny D?

Vitamin D is critical for strong bones, from infancy into old age. It helps the body absorb calcium from food. In older adults, a daily dose of "D" and calcium may help to prevent fractures and brittle bones.

Children need "D” to build strong bones and prevent rickets, a cause of bowed legs, knock knees, and weak bones.

Adding the vitamin to milk in the 1930s helped to nearly eliminate the disorder.

Vitamin D and Body Weight

Studies have shown that people who are obese often have low blood levels of vitamin D.

Body fat traps vitamin D, making it less available to the body. It's not clear whether obesity itself causes a low vitamin D level or if it's the other way around.

One small study of dieters suggested that adding vitamin D to a calorie-restricted diet may help overweight people with low vitamin D levels lose weight more easily.

D Baby Likes it Too

Breast milk is best, but it doesn’t have much vitamin D.

Breastfed babies, infants and children need 200 to 400 IU of vitamin D to meet their minimal needs.

Starting at age 1, babies drinking fortified milk may not any longer need a vitamin D supplement (food intake dependent).

Be careful not to give too much vitamin D to babies. High doses can cause nausea, vomiting, loss of appetite, excessive thirst, muscle aches, or more serious symptoms

Vitamin D and Cancer

Vitamin D levels are inversely associated with cancer. Though, it is hard to tell cause or reaction.

It’s too soon to make a strong case for vitamin D as an overall cancer-fighter. But newer studies suggest that people with higher levels of vitamin D in their blood may have a lower risk for colon and other cancers

Headlines tout vitamin D as a way to prevent breast and prostate cancer. But researchers don’t yet have enough evidence to say that the benefits are totally definitive.

Vitamin D may boost the risk of pancreatic cancer. The VITAL Study -- a Harvard university study -- of vitamin D and omega-3 is following 20,000 volunteers to find answers.

In the meantime, a healthy body weight, regular exercise, and the diet guidelines of the American Cancer Society may help prevent cancer

Does Your Ticker Keep-on Ticking?

Vitamin D and Heart Health

Low levels of vitamin D have been linked to a greater risk of heart attack, stroke, and heart disease.

Still, it’s not clear whether boosting vitamin D will reduce heart risks and how much vitamin D is needed.

Very high levels of vitamin D in the blood can actually harm blood vessels and the heart by increasing the amount of calcium in the bloodstream.

Have your blood levels tested and check them at least 1-2x/year

Test for D3 levels, not D2! [http://www.vitamindcouncil.org/about-vitamin-d/testing-for-vitamin-d/]

Vitamin D and Cognition

Older people are more likely to have vitamin D levels that are too low (lower 25%’tile).

Researchers found that older people with vitamin D deficiency performed poorly on tests of memory, attention, and reasoning compared to people with enough vitamin D in their blood.

Low serum levels of D correlates with mental function.

Continued studies are needed to learn if vitamin D supplements could prevent dementia or slow mental decline.

Supplementing with D at reasonable levels appears might help, cannot hurt…

D does not have to be for depression

Vitamin D plays a role in brain development and function.

One promising study showed that large doses (> RDA, but less than 10,000) of vitamin D could lessen the symptoms of mild depression.

But other studies show mixed results.

The best bet is to talk with your doctor about whether vitamin D could ward off the symptoms of depression.

Multiple Sclerosis and Vitamin D

Multiple sclerosis (MS) is more common far away from the sunny equator.

For years, experts suspected a link between sunlight, vitamin D levels, and this autoimmune disorder that damages the nerves.

One newer clue comes from a study of a rare gene defect that leads to low levels of vitamin D – and a higher risk of MS.

Despite these links, there's not enough evidence to recommend vitamin D (or not to recommend it for that matter) for the prevention or treatment of MS

Vitamin D, Diabetes and You

Some studies have shown a link between a low vitamin D level and type 2 diabetes -- the more common version of this blood sugar disorder. So, can boosting your vitamin D levels help ward off the disease?

Low levels of Vitamin D are strongly correlated with increased risk of impaired glucose tolerance (metabolic syndrome and obesity).

Lower the Vitamin D level, the worse the insulin sensitivity is.

Excess body fat may play a role in diabetes and low levels of vitamin D.

Vitamin D and Weight Status

There is a strong relationship between serum Vit D levels and weight status.

Obesity typically = hypovitaminosis for at least D in children, adolescents and adults.

Studies have shown that people who are obese often have low blood levels of vitamin D. Body fat traps vitamin D, making it less available to the body. It's not clear whether obesity itself causes a low vitamin D level or if it's the other way around. But one small study of dieters suggests that adding vitamin D to a calorie-restricted diet may help overweight people with low vitamin D levels lose weight more easily.

If it does not hurt and may help, why not add it?

Xeroderma pigmentosum

XP is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun. Some affected individuals also have problems involving the nervous system.

The signs of XP usually appear in infancy or early childhood. Many affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. Other affected children do not get sunburned with minimal sun exposure, but instead tan normally. By age 2, almost all children with XP develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder.

In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name, XP.

People with XP have a greatly increased risk of developing skin cancer. Without sun protection, about half of children with this condition develop their first skin cancer

by age 10. Most people with XP develop multiple skin cancers during their lifetime

Xeroderma pigmentosum II

The eyes of people with XP may be painfully sensitive to UV rays from the sun. If the eyes are not protected from the sun, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of eye cancer, XP is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.

Study with SPF 15 in XP plus sun-protective clothing

Average blood values of 25 OH D3 20 ng/ml or less (5 or < minutes a day of sun), a level of 55 or > in this population considered ideal. Blood levels of 1,25 DIOH Vitamin D averaged in low normal (~30 to 45 ng/ml).

Means in the face of minimal sun exposure, Vitamin D levels can be maintained.

Sunscreen – To PABA or not to PABA?

PABA – para-aminobenzoic acid (PABA) is a chemical found in the folic acid (B vitamin) family and also in several foods including grains, eggs, milk, and meat.

Often used in sunscreens - It is a UVB absorber, meaning it can absorb wavelengths between 290 and 320 nm.

Patented in 1943, amongst first ingredients used in sunscreens (1970’s).

Studies in 1980’s point to PABA increasing cellular UV damage. Controversial.

Not in major use anymore secondary to allergic dermatitis response (topical) and staining of clothes upon contact.

PABA found to interfere, reduce previtamin D3 production in the skin by at least 12%.

Topical D

Topical vitamin D (calcitriol) is a natural treatment for psoriasis. Analog, calcipotriene also used. Several studies found that topical use of calcitriol (3 mcg/g) ointment is safe and may be an

effective treatment for plaque-type psoriasis. The vitamin D analog called calcipotriene or calcipotriol has also been used as a treatment for chronic plaque psoriasis, either alone or in combination with corticosteroids.

Topical D3 (5000IU per gram) found to be absorbed and to enhance blood values. The average vitamin D levels in the treatment group before and after treatment were 12.05

ng/ml and 37.95 ng/ml, respectively. The average vitamin D levels in the control group before and after treatment were 10.4 ng/ml and 9.58 ng/ml, respectively. Demonstrates transdermal absorption.

“Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D(3)”.

Time out for D Checkup!

Disease incidence reduction by Serum D levels

Dining with D

Many of the foods we eat have no naturally occurring vitamin D.

Fish such as salmon, swordfish, or mackerel is one big exception -- and can provide a healthy amount of vitamin D in one serving. Cod liver oil too is a great source of D3. Three to four servings per week help to meet minimal D3 needs.

Other fatty fish such as tuna and sardines have some "D," but in much lower amounts.

Small amounts are found in egg yolk, beef liver, and fortified foods like cereal and milk.

Cheese and ice cream do not usually have added vitamin D.

Breakfast Starts with a “D”

Choose your breakfast foods wisely, and you can get a substantial amount of vitamin D. Most types of milk are fortified, including some soy milks. Orange juice, cereal, bread, and some yogurt brands also commonly have added vitamin D. Check the labels to see how much “D” you’re getting.

Dietary Sources of D

Food Sources of Vitamin D Table 3: Selected Food Sources of Vitamin D [11] Food IUs per serving* Percent DV** Cod liver oil, 1 tablespoon 1,360 340 Swordfish, cooked, 3 ounces 566 142 Salmon (sockeye), cooked, 3 ounces

447 112

Tuna fish, canned in water, drained, 3 ounces

154 39

Orange juice fortified with vitamin D, 1 cup (check product labels, as amount of added vitamin D varies)

137 34

Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup

115-124 29-31

Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more heavily fortified yogurts provide more of the DV)

80 20

Margarine, fortified, 1 tablespoon 60 15

Sardines, canned in oil, drained, 2 sardines

46 12

Liver, beef, cooked, 3 ounces 42 11 Egg, 1 large (vitamin D is found in yolk)

41 10

Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 0.75-1 cup (more heavily fortified cereals might provide more of the DV)

40 10

Cheese, Swiss, 1 ounce 6 2

Simplified Foods

Although few foods contain vitamin D naturally, some foods are fortified with it, which means that the vitamin is added to the food. Foods that contain vitamin D include: Cod liver oil salmon sardines egg yolk shrimp milk (fortified) cereal (fortified) yogurt (fortified) orange juice (fortified)

It can be hard to get enough vitamin D each day through sun exposure and food alone, so taking vitamin D supplements may help.

Are you Vitamin D Deficient?

Problems converting vitamin D from food or sunshine can set you up for a deficiency. Factors that increase your risk include: Age 50 or older

Dark skin

A northern home (above Atlanta, ~33.75 Latitude for the U.S., northern Ca.)

Overweight, obese, gastric bypass surgery

Milk allergy or lactose intolerance

Liver or digestive diseases, such as Crohn's disease or celiac

Vitamin D Deficiency

Vitamin D Deficiency

Most people with low blood levels of vitamin D don't notice any symptoms. Symptoms of bone pain and muscle weakness can mean you have a vitamin D

deficiency. However, for many people, the symptoms are subtle. Yet, even without symptoms, too little vitamin D can pose health risks. Low blood levels of the vitamin have been associated with the following: Increased risk of death from cardiovascular disease Cognitive impairment in older adults Severe asthma in children Cancer

A severe deficiency in adults can cause soft bones, called osteomalacia. The symptoms include bone pain and muscle weakness.

In children, a severe deficiency can lead to rickets and symptoms of soft bones and skeletal problems. Rickets is rare in the United States.

Testing Vitamin D

There's a simple blood test used to check your vitamin D level, called the 25-hydroxyvitamin D test.

Low D levels are typically <30ng/ml (<80nmol/l).

Generally, athlete’s aim to get blood levels around the 50 ng/dl, ideally above 80

Above 80ng/ml enhances intestinal calcium absorption

Can “in-home” test, here: http://www.vitamindcouncil.org/about-vitamin-d/testing-for-vitamin-d/

How much Vitamin D?

The recommended dietary allowance (RDA) for vitamin D is 600 IU (international units) per day for adults up to age 70. People aged 71 and older should aim for 800 IU from their diet. RDA is not set for optimal health.

Health professionals state, if you live north of the 33.75 latitude, your at greater likelihood for suboptimal or deficient levels.

Literature also suggests a safe zone for intake is no more than 10,000 IU (250 mcg) per day and safer to stay at or below 4,000 IU (100 mcg) per day.

The Endocrine Society issued clinical practice guidelines for vitamin D, stating that the desirable serum concentration of 25(OH)D is >75 nmol/L (>30 ng/ml) to maximize the effect of this vitamin on calcium, bone, and muscle metabolism.

It also reported that to consistently raise serum levels of 25(OH)D above 75 nmol/L (30 ng/ml), at least 1,500-2,000 IU/day of supplemental vitamin D might be required in adults, and at least 1,000 IU/day in children and adolescents.

Is it the D season?

Little to no previtamin D3 is produced before 8am or after 6pm (Boston, June tests) Between 8-10am and 4 to 6pm, previtamin D3 production is ~20% less than that produced

between the hours of 10am and 4pm. Noon in June on a cloudless day will produce 80% more previtamin D3 than same time

and same weather in October. Cloudy days reduce previtamin D3 by ~20% Vitamin D 25(OH)D circulates at 1000x that of 1,25(OH)2D. Half-life is ~2 weeks. As D levels fall, calcium uptake gets affected.

Vitamin D Roles

In addition to its primary benefits, research suggests that vitamin D may also play a role in:

reducing your risk of multiple sclerosis, according to a research study published in the Journal of the American Medical Association

decreasing your chance of developing heart disease, according to further research published in Circulation

helping to reduce your likelihood of developing the flu, according to more recent research published in the American Journal of Clinical Nutrition

What Can Hurt Your D Levels?

Some drugs cause your body to absorb less vitamin D. These include laxatives, steroids, anti-seizure and anti-cholesterol medicines.

If you take digoxin, a heart medicine, too much vitamin D can raise the level of calcium in your blood and lead to an abnormal heart rhythm.

It's important to discuss your use of vitamin D supplements with your doctor or pharmacist.

Understanding Vitamin D Blood Tests

Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health

<30nmol/L <12ng.ml

Associated with vitamin D deficiency, leading to rickets in infants and children and osteomalacia in adults

30.1 - 50nmol/L 12 - 20ng/ml Generally considered inadequate for bone and overall health in healthy individuals

>50nmol/L >20ng/ml Generally considered adequate for bone and overall health in healthy individuals

>125nmol/L >50ng/ml

Emerging evidence links potential adverse effects to such high levels, particularly if >150 nmol/L (>60 ng/mL)

�* Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL).

1nmol/l = 0.4ng/ml

The “sweet spot” for blood Vitamin D levels may be between 80 ng/ml and 125 ng/ml

The Latest on D from Dr. Manson

Harvard’s Dr. Joann Manson video – the latest on D

https://vimeo.com/100755600?mc_cid=23abbb7aa9&mc_eid=a315079ba7

Topically protective

Retinyl esters (form of vitamin A) concentrate in the epidermis.

May absorb ultraviolet radiation with a maximal at 325 nm.

In vitro model (hairless mouse model) tested.

UVB effects measured.

Humans tested (buttocks) at 4 MED dose

In vitro as effective as octylmethoxycinnamate (typical ingredient in sunscreens)

In humans, as effective as SPF 20 for preventing sunburn

Vitamin E

Vitamin E (alpha-tocopherol/tocotrienol) used for >50 years in experimental and clinical dermatology.

Mostly case reports in the literature with RDBCT lacking.

Experimental evidence suggests oral & topical has antitumorigenic, photoprotective and skin stabilizing properties.

Appears of value for evaluation in atopic dermatitis and or prevention of photocarcinogenesis.

Opportunity?

Ferulic acid

Ferulic acid is a plant antioxidant.

When mixed in a topical solution of 15% L-ascorbic acid + 1% alpha-tocopherol has benefits…

Appears to double photoprotection to solar induced erythema and sunburn by a factor range of 4 to 8-fold.

Inhibits apoptosis and reduces destructive enzyme activity (caspase 3 and 7).

Low molecular weight. Ferulic acid needs to be at 0.5% concentration for the 8-fold effect.

Worth considering for further confirmatory studies for use in SPF and or moisturizers.

Melatonin, more than for sleep

Melatonin, a pineal gland hormone helps to regulate sleep/wake cycles.

Melatonin can also be applied topically.

Vitamin C, E and melatonin tested in humans exposed to UVB

Vitamins alone, some protective effect.

Melatonin alone some protective effect.

Melatonin plus E and C enhanced photoprotection

More studies needed, potential use in SPF and moisturizers.

The famed Zebrafish

Zebrafish produce their own natural sunscreen. Analogous to melanin production in humans. Gadusol is the Zebrafish compound responsible for photoprotection. Gadusol named for the genus (Zebrafish = Gadus morhua L). Similar biological properties to ascorbic acid Known since 1981 Properties better defined now (anti-UVB, sunscreen effects) Not yet tested in humans for topical protection. Opportunity?

Good Websites for D-learning

http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ https://www.vitamindcouncil.org/blog/what-is-the-upper-limit-and-noael-and-are-they-justified/) http://www.vitamindsociety.org http://www.webmd.com/food-recipes/guide/calcium-vitamin-d-foods http://www.vrg.org/journal/vj2009issue2/2009_issue2_vitamin_d.php Canadian take on D http://www.dietitians.ca/Your-Health/Nutrition-A-Z/Vitamins/Food-Sources-of-Vitamin-D.aspx http://whfoods.org/genpage.php?tname=nutrient&dbid=110 http://www.ucsd.tv/vitamind/ The Rose Sheet (Cosmetics, Skin care and fragrances) – www.the-rose-sheet.com

Contact Information

Thank you very much to Guy Langer and the California Chapter of the Society of Cosmetic Chemists, all of you in attendance, and QPS-Miami Research Associates for supporting this presentation.

QPS – Dermatology Division - http://www.qps.com/sol-dermal-transdermal.php http://www.qps.com/docs/QPS_DERMAL-TRANSDERMAL_BROCHURE_2013.pdf?v=pW7H9yU06HE

QPS-Miami Research Associates www.miamiresearch.com

Dr. Douglas S. Kalman – 305 666 2368 (office) Douglas.kalman@qps.com