Mendelian randomization, a powerful tool to assess the effects of low vitamin D | Roger Seheult
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Randomized controlled trials, the gold standard for scientific research, are expensive and time-consuming. Another type of study, called Mendelian randomization, aims to establish causation by taking advantage of knowledge about a person's genes. Using a Mendelian randomization analysis, scientists determined that people carrying genetic variants associated with low vitamin D levels have higher mortality from respiratory tract infections and higher all-cause mortality. In this clip, Dr. Rhonda Patrick describes what Mendelian randomization studies are and how they are valuable instruments in the scientific toolbox.
Dr. Patrick: Another type of study that I love to cite and talk about, because as you had mentioned, previously, randomized controlled trials are very, very expensive to do, they're very difficult, you know, they take a long time. It's a challenge.
So another way of measuring more of a causative role, you know, of certain factors, and particularly, in this case, lifestyle factors or something that, you know, I call vitamin D lifestyle, because you're making it you know, from the sun, they're called Mendelian randomization studies. And essentially what they do is they measure, so everyone has, you know, different variations in their sequence of DNA in their genes. And these variations often are just a change in one DNA nucleotide, which is called the single-nucleotide polymorphism, or SNP for short, as you know. But for people listening and watching, there are many different variations in genes that convert, for example, 25-hydroxyvitamin D, the major circulating metabolite of vitamin D, into 1,25-hydroxyvitamin D, which is the active steroid hormone. And these changes in just one nucleotide of DNA in these genes are associated with lower circulating levels of 25-hydroxyvitamin D, because, you know, it's just, you know, different genes are doing different things. And sometimes genes get less active. And sometimes they're more active based on this, you know, sequence change.
So it's well known that these certain SNPs are associated with lower circulating 25-hydroxyvitamin D levels. And so there have been meta-analyses looking at people that have the SNP, didn't measure vitamin D levels at all, it's already known, they have lower circulating levels. So you can't say, Oh, you know, you're just measuring their low vitamin D. That's bio marketing and other health status. This is just genetics. We're just looking at a gene that's known to cause that. And these people have a much higher mortality from respiratory tract infections. They have a higher all-cause mortality, they have a higher cancer mortality. Cardiovascular-related mortalities is unchanged. But respiratory tract infections are much higher.
And so, that Mendelian randomization study, I love to cite that because it really is establishing causation because, you know, you're not just measuring vitamin D levels and then saying, well, maybe they're low in vitamin D because they don't go out and exercise or maybe they're low in vitamin D because they're, you know, obese and, you know, vitamin D is less bioavailable, which it is in obese individuals, as you mentioned.
So, the Mendelian randomization studies, in addition to the randomized controlled trials, I think another piece of evidence that hints towards possible causation of vitamin D being important for preventing respiratory tract mortality as well.
Dr. Seheult: Oh, that's amazing. I wasn't even aware of that. That's a great way of showing causation. And of course, they are working on some pilot studies that are trying to show randomization.
The death rate from all causes of death for a population in a given time period.
Important for the endocrine enhancing properties of exercise. Exerkines are exercise-induced hormonal-like factors which mediate the systemic benefits of exercise through autocrine, paracrine, and/or endocrine properties.[1]
- ^ Helge, Jørn Wulff; Moritz, Thomas; Morville, Thomas; Clemmensen, Christoffer; Dela, Flemming (2020). Plasma Metabolome Profiling Of Resistance Exercise And Endurance Exercise In Humans Cell Reports 33, 13.
An essential mineral present in many foods. Iron participates in many physiological functions and is a critical component of hemoglobin. Iron deficiency can cause anemia, fatigue, shortness of breath, and heart arrhythmias.
A type of study that analyzes the data derived from multiple studies. Meta-analyses apply objective, statistical formulas to identify a common effect.
A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.
One of four nitrogen-containing molecules that comprise DNA. A nucleotide consists of one of four chemicals, called a “base,” plus one molecule of sugar and one molecule of phosphoric acid. Nucleotides are typically identified by the first letter of their base names: adenine (A), cytosine (C), guanine (G), and thymine (T). They form specific pairs (A with T, and G with C), and their bonds provide the helical structure of the DNA strand.
A change in one nucleotide DNA sequence in a gene that may or may not alter the function of the gene. SNPs, commonly called "snips," can affect phenotype such as hair and eye color, but they can also affect a person's disease risk, absorption and metabolism of nutrients, and much more. SNPs differ from mutations in terms of their frequency within a population: SNPs are detectable in >1 percent of the population, while mutations are detectable in <1 percent.
A type of hormone derived from cholesterol. Steroid hormones are produced in the adrenal cortex, gonads, and placenta and have long half-lives in the body. They act as chemical messengers and regulate many physiologic processes, including the development and function of the reproductive system. Examples include estrogen, progesterone, and testosterone. The actions of the steroid hormones are mediated by the steroid hormone receptors.
The highest level of intake of a given nutrient likely to pose no adverse health effects for nearly all healthy people. As intake increases above the upper intake level, the risk of adverse effects increases.
A fat-soluble vitamin stored in the liver and fatty tissues. Vitamin D plays key roles in several physiological processes, such as the regulation of blood pressure, calcium homeostasis, immune function, and the regulation of cell growth. In the skin, vitamin D decreases proliferation and enhances differentiation. Vitamin D synthesis begins when 7-dehydrocholesterol, which is found primarily in the skin’s epidermal layer, reacts to ultraviolet light and converts to vitamin D. Subsequent processes convert D to calcitriol, the active form of the vitamin. Vitamin D can be obtained from dietary sources, too, such as salmon, mushrooms, and many fortified foods.
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