Hello The Weekly Paper readers! Thank you all for making last week’s post the most successful ever. This blog is finally gaining some serious traction and I want you all to know I truly appreciate the support.
This week’s question comes from my dad, who asks “Can you explain to me why we need vitamin C? Why do they say you need it when you’re sick?”
Vitamin C is known officially as L-ascorbic acid. This molecule is a dietary requirement and a chronic deficiency of vitamin C produces the famous disease “scurvy.” Principally, vitamin C has two main functions: enzyme co-factor and antioxidant.
In the body, vitamin C is used mostly as a co-factor in certain enzymes. A co-factor is a separate, non-protein component of an enzyme that is required for its function. Specifically, vitamin C acts as a reducing agent, which is a refers to its ability to reduce, or donate electrons, to other compounds and thus become oxidized (lose electrons) in the process. Within the realm of enzymes which utilize vitamin C, it acts as the electron donator (reducing agent) that returns the metal ions, which actually do the catalytic enzyme reactions, back to their proper reduced state. If the metal ions are allowed to be permanently oxidized, the enzyme then becomes useless and the reaction for which it is responsible no longer occurs. Put a much simpler way, oxidized = rusted, so the vitamin C prevents the metal ions from becoming rusted over and losing function.
So now that we understand that vitamin C allows metal ions in certain enzymes to function normally, let’s explore what enzymes actually use this mechanism. Primarily, vitamin C is used by enzymes involved in collagen, carnitine, norepinephrine, dopamine, and peptide hormone creation, as well as participating in tyrosine metabolism. As you might imagine, this is a fairly diverse group of enzymes; we still don’t fully understand the extent of vitamin C’s value across all relevant enzymes nor all of the mechanisms involved for each enzyme.
Of particular note, vitamin C plays an essential role in collagen formation. Without it, you cannot properly heal wounds and connective tissues can become seriously weakened. For example, the initial symptoms of scurvy largely stem from reduced collagen synthesis capacity. These include bleeding (due to compromised blood vessels), gum disease, poor wound healing, and bone issues, among others. As such, anyone having surgery should discuss with their surgeon the need to take vitamin C supplements before and after the procedure.
Vitamin C also has activity as an antioxidant, using its role as an easy donator of electrons to neutralize free radical (single electron) species on its own. Sadly, no one has comprehensively studied what impact this has on human health. But, it remains that vitamin C can act as an antioxidant and, as you are probably aware, reducing oxidative damage is a very important element of maintaining many aspects of our health.
Insofar as the immune system/treatment of disease is concerned, vitamin C’s role is much less clear cut. Clearly, its biological role is diverse and thus it could have a much greater role than we currently know. However, as of now what has been seen in the lab is extremely diverse and difficult to translate into clinical practice. Studies have shown vitamin C to reduce virus activity, suppress tumors, and regulate the immune system during infection (by influencing interleukin activity). But clearly, plenty of people take vitamin C regularly and still get sick. So it is hard to say, as of now, whether or not supplementing vitamin C for this purpose is really helpful to the immune system or is just merely a complement to an otherwise normal body response in healthy individuals.
The bottom line is, no matter what get your daily vitamin C by any means necessary. You can supplement, but even better you should get it from healthy foods that contain many other great nutrients such as broccoli, peppers, and kale. You’ll be happy you did.
Thank you for the question, dad! As always, if you have a question you’d like answered here, feel free to submit to directly at the link above.
Till next time, one love.
Hello readers! Sorry for the delayed post, been a hectic last few days getting my life arranged for my jaw surgery on Friday. This week’s question comes to Desiree, who asks “I’ve noticed I get sick more often when I’m really stressed about school. What exactly is happening that causes this and how can I avoid it in the future?” Well Desiree, I think most of us have experienced this phenomenon at one point or another. For some people, it can cause nastier problems than just more frequent colds. But, you’re spot on in your assessment that stress plays tricks on the immune system. Before we get to your question, we should first explore the relevant physiology of stress.
This response, commonly referred to as “fight or flight,” is meant to save your life in the event of an imminent threat or direct attack. It involves many different body systems and is a truly systemic in its effect. The complex interconnectedness is beyond the scope of this article, but the following is the basic rundown. I highly encourage independent research of this topic for a more complete picture.
The stress response is generated in the brain based on sensory input (ie. you see something scary coming towards you). The relevant signals are collected, processed, and travel to one or both of two locations. One is the locus coeruleus, which is responsible largely for initiating the stress response via production of norepinephrine in the brain. The other is the collective Raphe nuclei, which are responsible for, among other things, anxiety and are major serotonin producers in the brain. The subsequent release of neurotransmitters from one or both of these areas of the brain produce the stress response cascade throughout the rest of the body.
The signal produced by the brain has two major parts. First, direct neurological stimulation of the adrenal glands produces adrenaline very quickly. Second, the neurological signal initiated in the locus coeruleus is translated into hormonal signal by the hypothalamus. This then affects the pituitary gland and causes the release of ACTH, or adrenocorticotropic releasing hormone. This hormone enters the blood stream and stimulates the production and release of cortisol into the blood. Together with norepinephrine, which is also released by the adrenal glands along with adrenaline, these molecules are the dominant effectors of the stress response across the body. These molecules also feedback with the brain structures that originate them, creating a very complex web of effects that are not yet fully understood (ex. cortisol has an effect on serotonin production in the Raphe nuclei).
Adrenaline and norepinephrine (collectively a part of a group of molecules known as catecholamines) affect the sympathetic nervous system. It is not important to know what this is for the purposes of this discussion, just know it as one half of the body’s automatic systems. These molecules have a number of functions, namely opening the air passages, altering blood flow throughout the body, slowing digestion, and increasing heart rate. Many of the immediate physical effects you feel during a stressful situation are due to these because their release is much quicker than cortisol. This is also why adrenaline is used during anaphylaxis (allergic reaction), as it can open the narrowed airways and control the potentially deadly swelling.
Cortisol’s role is much different. Like the catecholamines, its job is to keep you alive when fighting for your life, but by a vastly different mechanism. Instead of priming the body to fight or move, cortisol’s main function is to augment its ability to produce and release glucose into the blood stream. It does this by both encouraging the breakdown of more complex storage sugars as well as increasing the processes that convert other molecules, such as proteins and fats, into glucose (known as gluconeogenesis). In other words, it provides the fuel you need to do whatever is necessary to survive, via the slash and burn method if necessary. It also has some inhibitory effects on body systems unnecessary in the short term, such as bone formation. Unfortunately, another one of cortisol’s inhibitory effects makes it the focus of this discussion for the remainder: immune system depression.
While it may seem counterintuitive to curtail the immune system when stressed, the reason for this is fairly simple once we understand the different nature of stress responses. The body has two basic types of stress: acute and chronic. Acute stress, caused by immediate stressors like being attacked or frightened, causes the release all of these molecules in tolerable amounts that temporarily empower us without a tremendous long term downside. Suppressing immune function in acute stress is smart because it holds off inflammation. As anyone who has injured themselves under stress can attest, function can be maintained through the injury until the stressful situation resolves. If the immune system were not held at bay during that time, the injury would quickly become immobile and hinder survival efforts.
However, chronic stress, with which many in graduate school or in dangerous/busy professions are intimately familiar, tips this balance towards the negative. If cortisol levels remain elevated continuously, the effects on the body due to continued suppression can cause a myriad of problems, including more frequent infections.
The immune suppressing function of cortisol has been utilized in medications for decades. Steroids (not the work out kind) such as prednisone and dexamethasone are commonly used in medicine to reduce inflammation, swelling, and the negative effects of autoimmune diseases. However, long term use of these drugs can have similar side effects as chronic stress. Thus, just as long term steroid use is often avoided due to its negative effects on the body, so too should chronic stress be avoided to prevent the same.
Unfortunately, cortisol is a natural part of the body and to attack it pharmacologically could be disastrous. So, stress management techniques are key to controlling its release by controlling the stimuli presented to the brain. Exercising, meditation, massage, acupuncture and other similar activities have been shown clinically to be beneficial for stress reduction. Given that they have minimal downside and often benefit quality of life, they are also the most advisable methods of stress control. If these prove ineffective, low doses of anti-depressant medications that affect the serotonin and/or norepinephrine in the brain may be helpful for this purpose (as it already is shown to be for people with severe anxiety).
Hope this helps, Desiree! Thank you for the question. As always, I encourage question submission via the link at the top of the page!
Till next time, que le vaya con Dios.
David DJ, et al. “Neurogenesis-Dependent and -Independent Effects of Fluoxetine in an Animal Model of Anxiety/Depression.” Neuron. 62(4); 2009 May: 453-455.
Laaris L, et al. “Stress-induced alterations of somatodendritic 5-HT1A autoreceptor sensitivity in the rat dorsal raphe nucleus — in vitro electrophysiological evidence.” Fundamental and Clinical Pharmacology. 11(3): 1997 May: 206–214.
Tsigos C, et al. “Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress.” Journal of Psychosomatic Research. 53; 2002: 865 – 871.
Valentino RJ, et al. “The Locus Coeruleus as a Site for Integrating Corticotropin-Releasing Factor and Noradrenergic Mediation of Stress Responses.” Annals of the New York Academy of Sciences. 697; 1993 Oct: 173-188.
Welch WJ, et al. “Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease.” Physiology Review. 72(4); 1992 Oct: 1063-1081.
This week’s question comes from Will all the way in Australia, who asks “I heard recently about how they cloned a human embryo for the first time to make stem cells. Can you explain how this works and what the potential implications are?”
Well Will, this is indeed a very exciting discovery and I am very glad you asked this question so soon after the announcement. For those of you who are not aware of this, a group of stem cell biologists led by Shoukhrat Mitalipov at the Oregon Health and Science University were able to recently clone a human embryo and make it divide. This had never been done previously and has been a long standing hurdle in the stem cell world. Previously, stem cells were had to either be harvested from fertilized embryos, growing fetuses, or somehow created or harvested from the blood or other organs. By having a cloned embryo grow normally, a near endless supply of genetically identical stem cells can be created from it. This would allow for custom stem cell sources that are completely compatible with an individual’s own cells, with potential to create new tissues and organs without the fear of rejection.
Now that we have the run down without much explanation, let’s dig into a few of the details.
First, let’s define what a stem cell actually is. Many of us are familiar with the term “stem cell” but are lost on their source, function, and overall role in the big picture. A stem cell is, at its core, a cell that creates other cells. When the human egg is first fertilized, it is a single cell and must divide many, many times to create the miniature human that emerges on the other end roughly 40 weeks later. All of these early cells are stem cells, which divide constantly, eventually taking shape as the many different tissues and organs we see as the end product. Once we are born, we still have many stem cells within our bodies. These cells are responsible for replacing tissues that are constantly lost or turned over. Bone marrow, for example, is filled with stem cells responsible for the many different types of blood cells. In the absence of stem cells to replace them, somatic (normal body cells) have varying rates of replication, with most only rarely, if ever, doing so.
However, not all stem cells are created equally. There are five major categories of stem cells: totipotent, pluripotent, multipotent, oligopotent, and unipotent. Totipotent stem cells are able to transform into any type of cell at any stage of development and are reflective of the cells present in our earliest developmental stages. Pluripotent stem cells all of the cell types present in the three germ layers, but cannot form the trophoblast. This means that the cell can produce any organ or tissue in the body (all organs and tissues come from one of the three germ layers), but can’t produce the cell layer necessary for implantation. Aside from trophoblast formation, totipotent and pluripotent cells have the same cell forming capacity. Multipotent stem cells are more restricted than pluripotent ones. They can transform into a variety of cell types but they are all normally related (ie. multiple different types of blood cells). Multipotent cells cannot transform into other types of tissues, but instead have a span of diversity across a given type. Following this line of reasoning, oligopotent stem cells are able to create an even more narrow set of cells, but can still create multiple different types. Like multipotent, oligopotent cells are restricted to related cells, but now the relation must now be much closer; for example, a given oligopotent stem cell could only create certain types of bone cells but not all of the cells responsible for a complete bone. Finally, unipotent cells only create one type of cell directly.
It is at this point then that we must make a change in our nomenclature to reflect the differences. While “stem cell” is used informally to refer to all types, each type has a particular name. Totipotent and pluripotent stem cells are the true stem cells and from now on will be the only cells referred to as such. Multipotent and oligopotent cells are known as progenitor cells and unipotent cells are known as precursor cells. While progenitor and precursor cells are extremely important to body function and absolutely have therapeutic value in their own right, this discussion focuses directly on stem cells so we will have to cast those aside for the time being.
So, returning back to the discovery, the method used was relatively simple (though obviously in real life it was incredibly complicated and took many years). This method, called somatic cell nuclear transfer (SCNT), involves removing a human egg cell’s nucleus and replacing it with that of a somatic cell. Given that an egg cell is normally unfertilized, it only comes with half the required genetic material. However, the other mechanisms involved in division and production of new cells are still active. By replacing the original nucleus with the somatic nucleus, which has the correct amount of genetic material, these mechanisms can be utilized without having to actually fertilize an egg. Prior to this study, most cells created this way could not get very far past the 8 cell stage for unknown reasons. Thus, the successful production of embryonic pluripotent stem cells by SCNT required an alteration of the given protocol. Interestingly enough, the addition of caffeine to the existing protocol (the exact details of which are not important) proved to be the major break through. Repeated experiments presented in the paper demonstrate that the protocol is reproducible using at least a small number of different cell types and with different egg donors, which is an important element for determining its applicability.
Clearly, this discovery could pave the way for the possibility of tremendous advances in regenerative medicine; the near-endless cultivation of pluripotent embryonic stem cells without actually having to create an embryo by the traditional method alleviates a tremendous amount of the ethical burden. Importantly, the lack of a trophoblast makes it physiologically impossible for the embryo to implant and grow in the womb; thus, it has not life potential. It is also important to note that by this method the pluripotent cells created are simply harvested as they grow, leaving the overall embryo structure intact. This creates what is known as a “cell line,” where stem cells can be produced by and harvested from the same set of embryonic cells in perpetuity.
However, there are some issues with this method that will prevent its wide applicability for at least the foreseeable future. Primarily, it is an incredibly labor intensive process to both transfer the nucleus and cultivate the cells, making any clinical application extremely expensive. Second, the system relies on donor eggs, which can range tremendously in quality. Thus the process would have to be repeated many times to ensure at least one creates viable cells. Finally, the discovery only demonstrates that the cells can be made. It does not make any comment on the effectiveness of the produced cells to form coherent, functional tissues or organs ready for transplant. In fact, we know little about this research beyond simply that it was successful in producing the intended cells; even that seems to be in doubt at the moment pending successful independent reproduction. It is safe to say that it will be a fair amount of time till these make it to the clinical arsenal, if ever since there are certainly other more readily available sources of the desired cells (albiet with much greater amounts of ethical and religious baggage). In short, it is definitely a positive step that overcomes a major hurdle in stem cell research, but still in the very early research stages. Only time will tell if it will truly live up to the tremendously lofty expectations.
Thanks for the question, Will! As always, if you want to submit a question feel free to do so at the top of the page.
Until next time, may the force be with you.
Original research paper:
Tachibana et al. “Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer.” Cell, 2013 Jun; 153: 1-11