This research review by Dr. Sinclair found increased CD38 responsible for the lower NAD+ levels as we age.
the major culprit is an NADase called CD38 whose levels rise during aging.
INFLAMMATION DRIVES MORTALITY
This study found inflammation is a better predictor of mortality than telomere length(r).
We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans(r).
DECREASING INFLAMMATION INCREASES NAD+ AND IS KEY TO HEALTHY AGING
Results from hundreds of tests for Intracellular NAD+ levels tell us that those with high inflammation levels (measured by HS-CRP) have less success raising NAD+ levels.
Lowering inflammation can help restore NAD+ levels on their own, and also allow NAD+ precursors to work even better.
By lowering inflammation along with use of effective NAD+ precursors, we have seen increases of 300% in some subjects vs 50% with NAD+ precursors alone.
NAD+ Supplements
NAD+
NMN
NR
- Each one utilizes different pathways for uptake in the body.
INCREASE ENDOGENOUS NAD+ PRODUCTION
Our bodies constantly recycle NAD+ in what is called the salvage pathway. The bottleneck in this process is NAMPT. Activating AMPK increases NAMPT to increase NAD+ through the salvage pathway.
Minimize NAD+ Consuming CD38
Apigenin
Resveratrol
Glutathione
CoQ10
- Powerful combination of anti-aging molecules that increase ATP to power your cells, boosts sirtuins and reduce CD38 which consumes NAD+.
- Boost cellular energy and your body’s own natural defenses. Boost mitochondria, the cells energy source and sirtuins, the body’s self repair enzymes.
- Prevents excessive loss of NAD⁺ by reducing the amount of circulating CD38, allowing NAD⁺ stores to remain at higher, more youthful levels.
Decrease Systemic Inflammation
CaAKG
Berberine
HLA
- Reduces systemic inflammation to minimize NAD⁺ consumption, prevent cellular senescence, slow the rate of age-related DNA methylation, and increasing levels of NAMPT which is responsible for the conversion of nicotinamide to NAD.⁺
Berberine Found to Increase NAD⁺ Levels, Lower Inflammation
In a study examining the effects of Berberine on NAD⁺ levels, it was found that Berberine increases an important enzyme responsible for the conversion of nicotinamide to NAD,⁺ called NAMPT.
“Berberine increases NAD+/NADH ratio through induction of NAMPT expression in C2C12 cells.” (1)
CaAKG Slows Effects of Aging and Reduces Inflammation
CaAKG works by slowing the rate of age-related DNA methylation and reducing the inflammation caused by senescent cells: two proposed reasons why we age.
“AKG suppresses chronic inflammation and induces secretion of IL-10 in T cells of female mice.” (2)
HLA Promotes New Cell Growth and Reduces Inflammation
Hyaluronic acid (HLA) is important for promoting the growth of new cells and tissues in the joint’s cartilage and bone, which thereby may reduce joint inflammation caused by injuries or tissue degeneration.
“The studies reviewed here show promising results for the use of HA in the treatment of inflammatory pathologies.” (3)
Destroy Senescent Cells
Fisetin
Quercetin
Spermidine
Powerful combination senolytic and AMPK activator. As you age, you accumulate more and more senescent cells.
Senescent cells are cells that refuse to die, creating toxins that cause inflammation and play a causal role in aging. These supplements have been shown to eliminate a significant number of senescent cells, which in turn reduces the inflammation and aging these cells cause.
In addition, Spermidine has been shown to protect and extend the lifespan of mice. According to Dr. David Sinclair, professor of genetics at Harvard and one of the leading longevity scientists, Spermidine can reduce disease and lower bioage by 5.7 years.
AMPK activators that increase NAD⁺ and promote mitochondrial biogenesis, which create new mitochondria that burn excess glucose and fats. This allows them to be used for energy instead of storing them in the stomach and elsewhere in the body.
AMPK Activators
- NAD+ levels decline due to chronic inflammation and by prolonged oxidative stress. This causes a reduction in NAMPT and NAD+ levels in multiple tissues. NAD+ is constantly being created and consumed, and lower levels contribute to multiple health issues. Providing support by stimulating internal AMPK production will help increase NAD+ production. Stimulating internal AMPK production helps restore and improve NAD+ levels. The following supplements offer AMPK & NAD+ support, anti-inflammatory and antioxidant benefits.
Fisetin
Epigallocatechin gallate (EGCG)
Pterostilbene
Astragaloside IV
Ellagic Acid
AMPK
AMPK is an important enzyme which senses energy levels (ATP) in the mitochondria. When energy is low, AMPK signals NAMPT to create more NAD+. The December 2011 e-publication AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network makes the point that AMPK plays a key role in controlling the aging process.
“Efficient control of energy metabolic homeostasis, enhanced stress resistance, and qualified cellular housekeeping are the hallmarks of improved healthspan and extended lifespan. AMPK signaling is involved in the regulation of all these characteristics via an integrated signaling network.”
FISETIN
Fisetin’s ability to clear out senescent cells has been shown to calm inflammation, improve physical function and increase lifespan in animals. It’s benefits in studies are vast: from improved metabolic function and blood sugar levels, pain reduction, lowered cholesterol levels and blood pressure, while improving bone density.
EGCG
Epigallocatechin gallate (EGCG) is a unique plant compound that helps reduce inflammation, support heart health, optimal blood pressure and cholesterol levels. Early research suggests it may play a role in improving neurological function and protect against brain diseases.
PTEROSTILBENE
Pterostilbene has been shown to demonstrate preventative and therapeutic health benefits. Pterostilbene, which is structurally similar to resveratrol, reduces oxidative stress and production of reactive oxygen species, which are implicated in numerous disease processes.
https://www.pterostilbene.com/pterostibene-potent-sirt1-activator/
https://pubmed.ncbi.nlm.nih.gov/27270300/
ASTRAGOLOSIDE IV
Astragaloside IV has strong antioxidant, anti-inflammatory, anti-apoptosis properties and numerous studies have shown it’s beneficial for brain health. In one study, it was found to enhance adult hippocampal neurogenesis, or the ability of the brain to increase neurons in the hippocampus. This process is very important for learning and memory as you age.
ELLAGIC ACID
Ellagic acid is associated with numerous health benefits from protecting brain function to lowering inflammation levels. Some animal and human studies suggest it may be useful in the treatment and prevention of age-related conditions, such as: type 2 diabetes, and neurodegenerative brain diseases.
APIGENIN
Apigenin is a powerhouse anti-aging compound, offering antioxidant, anti-inflammatory, antiviral, and neuroprotective properties, while boosting NAD+ levels, diminishing oxidative stress and improving cellular detoxification. Apigenin is a naturally-occurring bioactive plant polyphenol.
WHY IT'S IMPORTANT
As people get older, it becomes more difficult for the body to maintain proper energy production, mitochondrial function & repair mechanisms. Nicotinamide adenine dinucleotide (NAD+) is a molecule that is crucial for maintaining mitochondrial health and energy production and it diminishes in cells with age.
The diminished NAD+ levels are directly linked to age-related disorders, metabolic issues and cardiovascular dysfunction. An enzyme called CD38 plays a key role in the maintenance of NAD+ levels, as it’s the main enzyme responsible for the degradation of NAD+. Higher CD38 levels correlate with lowered NAD+ levels in the body. Senescent cell accumulation is also associated with an increase in CD38 and contributes to age-associated NAD+ decline.
STUDIES HAVE SHOWN
Researchers discovered that lowering CD38 levels through the use of a CD38 inhibitor, or by increasing NAD+ levels through supplementation with NMN, they were able to block the development of cardiovascular diseases in mice. By lowering CD38 levels, NAD+ levels increased and this led to lowering of blood pressure and lowering of blood vessel senescent cells. CD38 is a major consumer of NAD+ in the cells.
Mice lacking in CD38 or treated with the CD38 inhibitor apigenin had about 50% higher NAD+ levels.
In addition, apigenin has numerous small studies showing other possible benefits, including: improvements in depression and anxiety, memory and learning, weight loss and improved metabolic health.
Senescent Cells Increase CD38 and Decrease NAD⁺ Levels
As you age, you accumulate senescent or “zombie” cells, cells that have reached their limit of cell division and would normally be swept away and replaced by younger cells. Instead, these cells hang around and begin to secrete toxins called SASP factors which increase systemic inflammation.
The rising levels of inflammation cause an increase in an enzyme called CD38, a big consumer of NAD⁺, causing systemic NAD⁺ levels to drop.
“Our data suggest a link between cellular senescence and NAD⁺ decline in which SASP-mediated upregulation of CD38 can disrupt cellular NAD⁺ homeostasis.” (1)
Fighting Declining Levels of NAD⁺ with Apigenin
Apigenin prevents excessive loss of NAD⁺ by reducing the amount of circulating CD38, allowing NAD⁺ stores to remain at higher, more youthful levels.
We showed that the activity of CD38, but not PARP, increases in several tissues during the aging process, and that genetic ablation of CD38 protects against age-related NAD⁺ decline and, mitochondrial dysfunction.” (2)
Inhibition of CD38 Increases Lifespan and Healthspan in Mice
Studies have found that lowering CD38 levels (using a CD38 inhibitor called 78c) not only increased NAD⁺ levels but also improved mitochondrial function and endurance performance.
“Aged mice (2 years old) had lower tissue NAD⁺ levels, and worse glucose tolerance compared with younger mice. 78c promoted a significant increase in NAD⁺ levels in tissues of aged mice.” (3)
Sleep
https://renuebyscience.com/liposomal-apigenin-sleep-study-results/
On average, participants doubled their deep sleep duration after beginning to take LIPO Apigenin.
Apigenin is an antioxidant with reported effects on the quality and the quantity of deep sleep. Chamomile, for example, which has been used as a sleep aid for centuries, contains apigenin.
BERBERINE
Berberine affects the body at the molecular level and has a variety of functions inside cells. One of the main functions is activating an important enzyme called AMPK, which regulates metabolism.
Berberine is one of the most promising interventions to slow the accumulation of senescent cells by inducing autophagy. Autophagy is an evolutionary self-preservation mechanism through which the body can remove dysfunctional cells and toxic proteins responsible for many age-related chronic diseases and recycle parts of them toward cellular repair and cleaning.
Berberine’s benefits extend beyond the induction of autophagy and include optimizing metabolic pathways and upregulating the molecules that maintain the epigenome. It has also been shown to increase NAD+ levels through its activation of the AMPK enzyme.
Berberine’s unique ability to lower blood sugar, stimulate weight loss, lower cholesterol levels and improve heart health, have made it an increasingly popular supplement.
WHY IT'S IMPORTANT
Blood sugar and insulin problems, weight gain and other metabolic issues and diseases like diabetes are common in the aging population. These issues contribute to a range of health problems. Chronic high blood sugar levels can cause damage to the body’s tissues and organs, leading to numerous health problems and contributing to a shortened lifespan. Lifestyle and dietary interventions play an important role in maintaining metabolic health. Senescent cell levels increase with inflammation, metabolic issues, obesity, diabetes and insulin resistance.
STUDIES HAVE SHOWN
Numerous studies show that berberine significantly reduces blood sugar levels in people with type 2 diabetes. It is often recommended as a natural alternative to the prescription drug Metformin. Berberine works by decreasing insulin resistance, helping the body to break down sugars inside cells, decreasing sugar production in the liver, slowing down the breakdown of carbohydrates in the gut, while increasing beneficial bacteria. In one study of diabetic patients, those taking berberine had a 20% lower fasting blood sugar level and went from diabetic to normal levels. It’s also been shown to improve cholesterol levels and triglycerides.
It’s currently being studied as a potential senolytic. In a study, activation of AMPK with berberine significantly prevented the development of senescence.
CALCIUM ALPHA KETO GLUTURATE
Calcium Alpha-Ketoglutarate (CaAKG) shows great promise in numerous studies and plays an important role in the aging process.
WHY IT'S IMPORTANT
Aging is associated with a dysregulated epigenome. Epigenetics is the study of how cells control gene activity without changing the DNA. Epigenetic changes play a part in whether genes are turned on or off. When dysregulated, this leads to epigenetic errors and conditions such as cancers, metabolic disorders and degenerative diseases. Epigenetic dysregulation is closely correlated with aging.
STUDIES HAVE SHOWN
CaAKG is a regulator of epigenetic processes and provides energy to the mitochondria. It works in numerous pathways in the body and helps build muscle and heal wounds. It plays a role in amino acid metabolism and carbohydrate metabolism, helping cells maintain metabolic flexibility. A number of studies have shown that CaAKG influences aging and in numerous studies it has extended lifespan in organisms. In one study, dietary supplementation increased both median and maximum lifespan in flies. In a recent study, researchers found that mice given CaAKG experienced a 12% increase in lifespan, and a 46% reduction in frailty, and 41% increase in healthspan.
CaAKG is often given to athletes and bodybuilders in order to boost physical endurance and energy by providing fuel to the mitochondria.
CaAKG has also been studied for its ability to enhance autophagy. Autophagy is the body’s way of cleaning out damaged cells, and the body’s autophagic activity declines with age, contributing to the development of disease.
Calcium Alpha-Ketoglutarate (CaAKG) works by slowing the rate of age-related DNA methylation and reducing the inflammation caused by senescent cells : two proposed reasons why we age.
CaAKG also contributes to metabolism, providing energy for cellular processes. It helps stimulate collagen and protein synthesis and influences age-related processes including stem cell proliferation. Increasing CaAKG in the body supports your liver and its detoxification abilities.
CaAKG Lowers Inflammation – Shown to Increase Healthspan & Lifespan In Mice
In a study at the The Buck Institute for Research on Aging, CaAKG was shown to significantly extend the lifespan and healthspan in mice.
“We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines.” ⑴
Chronic inflammation has a significant impact on NAD⁺ levels — CaAKG can lower inflammation and preserve NAD⁺ levels which may lead to a healthier, longer life.
FISETIN
Fisetin is a potent compound that may help slow degenerative aging processes by selectively destroying and clearing out senescent cells. Fisetin is a natural polyphenol and antioxidant and it’s main function is to get rid of senescent cells and lower systemic inflammation.
WHY IT'S IMPORTANT
Aging is associated with the buildup of senescent cells. Senescent cells are dysfunctional cells that are difficult to clear out of the body. When they aren’t cleared out, they cause damage to surrounding healthy cells by releasing proinflammatory substances. Senescent cell accumulation contributes to age-related diseases, such as: glaucoma, liver cirrhosis, Type 2 diabetes, cancer, sarcopenia, osteoarthritis and cardiovascular disease. The accumulation of senescent cells also contributes to a decline in immune function.
STUDIES HAVE SHOWN
Fisetin’s ability to clear out senescent cells has been shown to calm inflammation, improve physical function and increase lifespan in animals. It’s benefits in studies are vast: from improved metabolic function and blood sugar levels, pain reduction, lowered cholesterol levels and blood pressure, while improving bone density. Studies have also demonstrated its ability to prevent the breakdown of collagen from UV/sun exposure.
Senescence
When cells no longer divide, they become mostly useless and start to build up in your body triggering inflammation, gradually impairing your cellular function, and increasing your risk of age-related disease.
Scientists refer to these as Senescent cells but are more commonly called “Zombie” cells. They are like little poison factories that do no useful works but instead emit cytokines, which trigger inflammation in neighbor cells.
GLUTATHIONE
Glutathione is the body's master antioxidant and optimal levels are vital to healthy aging and disease prevention.
WHY IT'S IMPORTANT
Glutathione deficiency is recognized as a risk factor in coronary artery disease, asthma, neurodegenerative disorders, cognitive-behavioral problems, and various types of cancer. As you age, your body requires higher levels of glutathione for optimal health.
STUDIES HAVE SHOWN
Benefits in mitochondrial function, improvement, lessened inflammation, improved endothelial functioning, improved exercise capacity and lowered body-fat and waist-circumference.
Glutathione is a naturally occurring intracellular antioxidant found abundantly in nearly every cell in your body. This potent molecule plays such a crucial role in your body. There is increasing awareness of its utility in mitigating the body’s toxin load. 3
The Master Antioxidant
Known as the “Master Antioxidant,” its levels decrease as a result of aging, stress, and toxin exposure.
Because glutathione can be broken down rapidly in the digestive tract, it is important to select a glutathione supplement that is formulated to survive exposure to digestive enzymes and be well absorbed. The liposomes surround each molecule and protect the core ingredients from the digestive system while increasing its transport and uptake by your cells.
Research Reveals Liposomal Glutathione Is More Effective
Clinical research aiming to improve Glutathione concentration requires sufficient Glutathione absorption and delivery.
Results from two recent studies showed that liposomal formulation is more effective at raising blood Glutathione levels in humans than non-liposomal Glutathione. 1,2 Both studies report a very rapid decline in the bioavailability of non-liposome-encapsulated Glutathione compared to liposomal Glutathione.
HYALURONIC ACID
Hyaluronic acid’s benefits are multifaceted & supplementation has shown great promise in clinical studies, with improvements in tissue hydration & skin appearance, joint health and improvements in mobility.
A key molecule involved in skin hydration, joint health, and bone integrity, the natural production of Hyaluronic Acid rapidly declines by up to 50% by the time you’re 50 years old.
Studies show that consuming extra hyaluronic acid boosts the body’s natural production.
WHY IT'S IMPORTANT
The physical impacts of aging can be difficult and painful to deal with. Aging is associated with joint & mobility issues, stiffness, pain and numerous osteoarthritic conditions. Hyaluronic acid is a naturally occurring protein and it’s found in every tissue in the human body. Approximately half of the hyaluronic acid in your body is found in your skin and synovial fluid, which is contained in the knees and other joints. It plays an important role in joint lubrication and mobility. Declining levels in the body are associated with joint pain, inflammation and disability. Hyaluronic acid levels also play an important role in your skin’s appearance. Skin aging correlates with the loss of skin moisture and an increase in wrinkles and skin laxity.
The key molecule involved in skin moisture and it’s youthful appearance is hyaluronic acid.
STUDIES HAVE SHOWN
Lower levels of hyaluronic acid in the knee joint was shown to be directly correlated to pain and the degradation of synovial fluid. Synovial fluid's job is to provide cushion and lubrication for joints. Synovial fluid contains high levels of hyaluronic acid and that aids in maintaining the integrity of the joint, lessening inflammation and preserving its function. A 2015 study reported that a three-month course of hyaluronic acid supplementation provided relief to overweight adults dealing with osteoarthritis. They experienced a steep reduction in inflammatory proteins called cytokines, and an increase in the concentration of hyaluronic acid in joint fluids, a reduction in pain and improvement in joint function. Two animal studies have shown that hyaluronic acid supplements can help to slow down the rate of bone loss in rats with osteopenia. Skin improvements were also noted in numerous studies.
A 2017 study showed a reduction in wrinkle depth and volume, improvement in skin’s luster, appearance and suppleness, after 12 weeks of treatment with hyaluronic acid supplements.
QUERCETIN
A powerful anti-inflammatory, known for its potent antioxidant, antiviral and antihistamine properties. As a plant pigment, Quercetin belongs to a group of plant compounds called flavonoids. Flavonoids are compounds commonly found in: vegetables, fruits, grains, tea, and wine. Flavonoids are associated with a wide variety of health benefits.
WHY IT'S IMPORTANT
Oxidative stress is a process that occurs due to an imbalance between antioxidant activity and free radical activity in the body. When free radicals accumulate, they are kept in check by antioxidants. Substances that generate free radicals include: food, medicine, pollution and other chemicals. If the antioxidants can't maintain a balance and the free radical accumulation worsens, this leads to damage to your DNA, fatty tissues and proteins in your body. The damage contributes to an array of age-related issues: from diabetes, blood vessel hardening, hypertension, neurological conditions and heart disease.
STUDIES HAVE SHOWN
Research on quercetin suggests it can neutralize free radicals while reducing the body’s oxidative damage. It’s also been studied for an array of other potential health benefits, from possible blood pressure reduction, blood sugar regulation, improvements in cholesterol levels, protection against degenerative neurological conditions often associated with aging, lessened pain and stiffness related to joint function, and allergy-symptom relief.
It’s also been shown to support cellular energy production through mitochondrial biogenesis, or the production of new mitochondria. Researchers have discovered it’s a powerful CD38 inhibitor.
It’s also becoming increasingly popular for allergy-sufferers. Quercetin inhibits the production and release of histamine and other allergic and inflammatory substances by stabilizing cell membranes of mast cells and lowering inflammation with the allergen-induced immune response.
RESVERATROL
A popular sirtuin-activator that can boost cellular energy and improve mitochondrial function, while offering cardiovascular & immune system support.
WHY IT'S IMPORTANT
Sirtuins play a key role in regulating metabolic health, circadian rhythm, detoxification and cellular aging. Sirtuin-activating compounds are being studied for the treatment of a variety of inflammatory and metabolic disorders. Resveratrol is a sirtuin-activator which plays a key role in regulating metabolic health, circadian rhythm, detoxification and cellular aging. Sirtuin-activating compounds are being studied for the treatment of a variety of inflammatory and metabolic disorders.
Inflammation is one of the driving forces of aging and age-related diseases. Although it has a notable impact on the aging population, it also impacts younger people as well. Common symptoms of inflammation include: fatigue, depression, gastrointestinal issues and infections. Unhealthy dietary choices, stress, smoking and other pollutants can contribute to inflammation. Over time, chronic inflammation can lead to damaged DNA, mitochondrial issues and disease development.
STUDIES HAVE SHOWN
Resveratrol’s benefits are vast and studies have shown evidence of its positive and protective impact on heart disease, metabolic syndrome and neural degeneration in animal studies.
One key feature of resveratrol is its ability to activate sirtuins. It also improves cellular energy and mitochondrial function, while offering cardiovascular & immune system support. In studies, resveratrol has increased the lifespan of fish, fruit flies, worms, yeast and mice which were fed a high-calorie diet. Studies on resveratrol have reported a reduction in age-associated symptoms, plus the prevention of early mortality in obese animals and in another study it slowed down and prevented cognitive deterioration in mice.
CURCUMIN
Curcumin is the active compound in turmeric, and has been studied extensively for multiple conditions. It has been shown to benefit inflammatory conditions, metabolic syndrome, pain, and to help in the management of inflammatory and degenerative eye conditions. Most of the benefits of curcumin supplementation are derived from its antioxidant and anti-inflammatory effects. In one randomized double-blind placebo-controlled human, supplementation with curcumin improved working memory, performance and sustained attention. Biomarkers also showed a significantly reduced total and LDL cholesterol.
It’s also been studied for pain and inflammation-related symptoms from arthritis. One study showed that curcumin, when taken for 8-12 weeks at 1000mg/day, offered pain-relief and symptom-relief that was similar to that of taking ibuprofen and diclofenac sodium.
VITAMIN D3/K2
Vitamin D is the only vitamin out of all 13 essential vitamins that the body can manufacture on its own. Many people become deficient in vitamin D because they don’t get enough sunshine.
One of the many roles of vitamin D is to promote calcium absorption, allowing for proper bone mineralization and growth. It also has other diverse roles throughout the body, including the reduction of inflammation and supporting immune function.
Proper functioning of the immune system depends on sufficient levels of vitamin D. Both Vitamin D and Vitamin K2 play central roles in calcium metabolism, which is vital for maintaining healthy bones, for regulating heart rhythm, blood pressure and other vital cellular functions.
WHY IT'S IMPORTANT
As you age, your skin’s ability to manufacture vitamin D from the sun diminishes and this can lead to a vitamin D deficiency, which is a common problem. People who live in colder climates and those who work indoors are more likely to suffer from it. In addition, people with darker skin are also less able to produce vitamin D from sunlight and are at a higher risk for deficiency.
Symptoms of a vitamin D deficiency in adults include: tiredness, aches and pains, bone or muscle pain, weakness, stress fractures, illness and depression.
STUDIES HAVE SHOWN
Correcting a deficiency is important for multiple reasons. The vitamin is so critical to immune function that low levels are associated with an increased susceptibility to infection, disease, and immune-related disorders. Research shows that vitamin D deficiency is also linked to decreased lung function, which may impact your body’s ability to fight respiratory infections.
It also plays an important role in regulating mood and warding off depression. In one study, scientists found that vitamin D supplementation improved symptoms for those suffering from depression.
Vitamin D has other roles in the body, including reduction of inflammation as well as modulation of such processes as cell growth, neuromuscular and immune function, and glucose metabolism.
Vitamin D Deficiency is Common
“Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency. This pandemic of hypovitaminosis D can mainly be attributed to lifestyle and environmental factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin.” ⑴