The Global Obesity and Metabolic Syndrome Pandemic: What’s At the Root??

Fat Chance Cover

 

Hi everyone, Happy Labor Day weekend! Almost two months ago in one of my classes, we were assigned to read and analyze a diet/health book, write a research paper on it along with our analysis, and create a video communicating our findings. This turned out to be one of my favorite assignments in my program so far because there are countless books, blogs, and even journal articles published that go unquestioned. Both the public and physicians sometimes take the findings and advice and run with them without a second thought, dramatically adjusting their diets and lifestyles based upon what is shared. As a future practitioner who will undoubtedly have patients whose physical and mental health are negatively affected by the dogma put forth in such writing, a large part of my success in treating them will rely upon being able to effectively communicate why they feel the way they do, and why they need to shift their beliefs and try something new.

 

As part of any review, one needs to look at the background of the author (their credentials, affiliations, is there a financial angle, etc.), the science behind the central theory of the book, if the author uses peer-reviewed scientific references to back up their claims, and if there is other supporting research outside of what the author cites to further substantiate their advice. There are much more in-depth ways to evaluate journal articles, but there’s no need to delve into them on this post. The video explanation was a little difficult for me but I enjoyed it; we were only given ten minutes to effectively summarize our findings, and it was challenging to recall the complicated science and communicate it in a way so that everyone can absorb it. You can watch my video and read my written review below, and let me know what you think!!!

 

 

Dr. Robert Lustig, the author of Fat Chance, boasts an impressive résumé that has prepared him to effectively articulate and drive home the biochemical principles at the root of the global obesity pandemic. Earning his undergraduate degree from MIT and medical school training from Cornell University, along with many years spent working at St. Jude’s hospital treating children with hypothalamic disorders, Lustig is a neuroendocrinologist and an expert on metabolic disease.

 

Further, he has taught at the University of Wisconsin, University of Tennessee, and currently at the University of California San Francisco as a Professor of Pediatrics in Endocrinology. To boot, he has authored over 85 peer-reviewed articles. This distinguished amalgam of experience not only makes his work credible, but, given his teaching and writing experience, he is well-equipped to simplify complex biochemical pathways so the “layperson” can understand the dynamics of obesity and Metabolic Syndrome (MS).

 

The inception of his work in metabolic disease occurred while witnessing children become acceleratedly obese following damage to their hypothalamus as a result of diminished leptin signaling. Part of successful treatment for these children relied upon pharmaceutically-induced suppression of insulin secretion, causing them to become more active, eat less, and lose weight. Years later, this framework transcended to obese individuals without any form of hypothalamic disorder or damage, who Lustig treated successfully.1

 

Appropriately, the central theory of his book rests on debunking the world’s notion that obesity is a personal responsibility caused by eating too much and not exercising enough. To Lustig, a calorie is not a calorie. Biochemistry influences these behaviors and, without altering it, one can never improve their health. Referencing over 300 peer-reviewed scientific studies and books to support his theory (seven of which are his own work), along with clinical anecdotes of his patients woven through each chapter, Lustig is not pushing any fluff or conjecture upon the reader. Specifically, he expounds upon the “battle royale” between the Ancel Keys2 and John Yudkin3 studies, claiming Keys as the wrongful victor and how these findings incorrectly influenced our society to avoid dietary fat. Sugar, as Yudkin cited, is “pure, white, and deadly,” and the true villain in this story.

 

Lustig attributes the prevalence of metabolic disturbances today to the increased quantity and decreased quality of our food and beverage supply, specifically four main items: trans fats, branched-chain amino acids (BCAAs), alcohol, and most notably, fructose. He also emphasizes that fiber has all but been eliminated from most Americans’ diets. Cut the sugar, boost the fiber, and exercise; this is the central theory behind Fat Chance and on solving the global obesity and MS pandemic. In the next paragraphs, I will explain the biochemistry involved in arriving at this metabolic cul-de-sac and how his simplified recommendations can navigate one’s body out on to Easy Street.

 

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Our hormones control our behavior. Many women (and men!) can attest to this if they have ever experienced or witnessed uncontrollable mood swings prior to or during menses. For the health picture Lustig is describing, insulin and leptin are the two key players, and the hypothalamus is the conduit, specifically the vagus nerve.

 

Insulin is our energy storage hormone. When we consume carbohydrate-containing meals, our blood glucose elevates, and the pancreas secretes insulin to escort the glucose into the cells for energy, store the protein into our muscles, and fats as triglycerides. The more insulin pumping, the more fat storing.4 Leptin is a protein made and released by our fat cells that communicates with the hypothalamus regarding our satiety, fat storage amount, and nutrient metabolism.5 This messaging is part of our biochemistry and, in turn, influences our behavior.

 

In a normal, healthy individual, they eat, insulin rises, and energy goes to their fat cells. Leptin senses that their fat cells are energized, reports back to the hypothalamus and says, “We’re fed and happy, we don’t need anymore, so let’s start to do work and burn this energy.”6 The hypothalamus then tells the pancreas to stop pumping insulin by reducing our appetite so we don’t take in any more food. Insulin is leptin’s antagonist;7 when insulin levels are chronically high, the hypothalamus only sees this message. Leptin cannot get the hypothalamus’ attention, so the hypothalamus misses the memo, continuing to tell our body, “I didn’t hear you’re full or fat yet. In fact, it seems like you’re starving. Don’t burn anything, don’t do anything, and store all the fat you can because you need to survive!”8

 

Lustig reiterates that chronically high insulin levels are a result of increased consumption of fructose, trans fats, and alcohol, and its effects on our mitochondria. As the interpretation of Ancel Keys’ study led to the reduction of dietary fat in our food supply, increased amounts of sweetener were incorporated in order to make things palatable. This led to greater amounts of sucrose (50% glucose, 50% fructose) and high fructose corn syrup (55% fructose, 45% glucose) dominating nearly every manufactured food in our supermarkets.

 

Glucose metabolism is insulin-dependent and is metabolized by all organs, including the brain, for energy. What is left is then sent to the liver for glycogen formation. Fructose, on the other hand, goes straight to the mitochondria of our hepatocytes. Further, our liver requires three times as much energy to metabolize fructose, depleting our ATP stores. Similarly, four times as many calories of alcohol reach the liver versus that of glucose, which heads straight the mitochondria as well.9 To compound things further, trans fats, synthetic fats created to preserve shelf life and stability of processed foods, cannot be broken down by our mitochondria.10 In addition, taste and expiration dates were favored at the expense of fiber in our processed foods. Fiber inhibits the rate of flux of nutrients from our intestines to our bloodstream; the onslaught of these stresses to the mitochondria is decreased when our food contains it. Without it, our mitochondria must work harder and faster, and as a result, become overwhelmed and inefficient.11,12 With this lethal combination, our liver enzymes are overactive, inflammation and insulin resistance develop, and our leptin signaling becomes disrupted. We get sick or fat, or both.

 

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Eating is a pleasurable experience, no doubt. When we eat something we love, dopamine is released, and we experience pleasure.13 Both leptin and insulin, when they rise, cue the brain to stop releasing dopamine and clear it out of the synapses where it is active, respectively.14,15 However, in metabolic syndrome, where one is hyperinsulinemic and thereby blocking leptin signaling, the brain once again misses the memo to shut down all parts of this reaction. As a result, eating continually triggers the same feeling of reward – not easily thwarted – and one keeps eating and eating.

 

By avoiding sugar and increasing fiber, we avoid these consequences and allow our mitochondria to get back on track. By adding exercise to the equation, one builds muscle and new mitochondria, decreases visceral fat, improves insulin levels and sensitivity, and reignites proper communication between leptin and the hypothalamus.16,17 Exercise also increases the rate of our Krebs cycle – all of which burns energy and fats faster and more efficiently. We become healthier, skinnier, or both.

 

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Most of Lustig’s references cover the most relevant and comprehensive studies and literature that exist on the topic of MS. I found additional supporting research that backs up the science he so eloquently supplies along with his traditional remedy of diet and lifestyle change. Four studies discuss increased fructose consumption as a causative factor in metabolic syndrome,18-20 which is significantly hastened by the removal of fiber from the diet.21 Two studies emphasize the risk heavy alcohol consumption poses on development of MS,22 differing in severity by alcohol type.23 One study highlights the improvement of metabolic syndrome scores in those with T2DM and MS as a result of combined aerobic exercise and strength training.24 Again, there are countless studies that confirm Lustig’s “theory,” as it is hard science.

 

Slightly off topic, I found a study that showed a significant correlation between decreased marital satisfaction of women and their risk for developing MS as a result. Interestingly, the same was not reflected for men.25

 

As for my opinion, I would not categorize Fat Chance as a “diet book,” by any means; it is a sound scientific explanation of metabolic disease, and Lustig does a superior job of communicating where we have gone wrong. Ironically, where this book does lack a punch and where he loses his credibility is in the actual dietary recommendations section. He provides general practices: avoid sugar (specifically fructose), eat more fiber, eat real food, etc. He also provides a “red, yellow, and green” status system for foods that should be consumed sparingly, three to five times a week, and everyday, respectively. This yellow status column introduced my first bone to pick with Lustig.

 

Many items on the yellow list are processed, pro-inflammatory, refined foods. Kashi? Cheerios?! Canola oil? Egg beaters? Salami??? Lunch meats? He also red-lists nutritious foods like coconut oil and palm oil without any reasoning to explain their place on the list. Oddly, he also places diet drinks and noncaloric sweeteners on the “limbo list,” which I assume means that the jury is still out on these. This disappointed me, as a 2008 study26 shows that noncaloric sweeteners disrupt innate physiological responses to glucose and further compound factors leading to MS. Perhaps his strict science background relating to biochemistry limits his knowledge to the insulinogenic properties of food at the expense of other effects these types of food have on our overall health. The book can only cover so much, though. And, to his credit, his green list is ripe with grassfed meats, pastured eggs and poultry, wild fish, whole grains, fruits and vegetables, and organic dairy.

 

The other bones I have to pick with the author involve his negative views on BCAAs and his take on micronutrient supplements.

 

Lustig explained that BCAAs (the essential amino acids valine, leucine, and isoleucine), when in excess, head straight to our hepatocytes’ mitochondria to be burned for energy and lead to fat synthesis. He also cited a study that correlated those with MS having higher levels of these amino acids in their bloodstream.27 This is correlation and not causation, though. In my research, I have found that plasma levels of BCAAs fluctuate to meet demands of different metabolic pathways.28,29 In skeletal muscle, BCAAs are transaminated to ketoacids, which are then broken down and oxidized by the branched-chain ketoacid dehydrogenase enzyme (BCKD) to eventually feed into the Krebs cycle for energy production. Increased insulin levels, which are a hallmark of obesity and MS, inhibit BCKD activity.29 Metabolic acidosis, which is seen in tandem with the catabolic states characteristic of obesity and insulin resistance,30 also inhibits BCKD.28 Depression of the enzyme’s activity minimizes complete BCAA oxidation, causing them to accumulate in the blood, thus being one rationale as to why plasma levels are elevated in these states.28,29

 

Furthermore, a study31 by Macotela et. al on rats with Metabolic Syndrome fed a high fat diet for eight weeks responded to doubling of dietary leucine alone, reversing their metabolic abnormalities and upregulating their insulin sensitivity. This being said, I would remove BCAAs from the list of culprits, as their plasma elevations are a downstream effect, and can even be beneficial to the system.

 

As for micronutrient supplements, Lustig says on page 156, “Micronutrients matter – the biochemistry says so – except they don’t work when provided as supplements in clinical trials. . . And nutritional supplements can’t reverse that which has previously been destroyed.” As a clinical nutritionist in training, I beg to differ.

 

Chromium is known for its role in insulin sensitization. When insulin is secreted, it rushes to receptors on the cell like a lock-and-key to transport glucose out of the blood and into the cells. The insulin receptor, tyrosine kinase, is dependent upon chromium for activation and functionality, in order to allow for insulin to unlock the cell and import glucose. Without chromium, this sensitization is lost and insulin resistance can occur.28 Understandably, those deficient in this nutrient would have decreased insulin sensitivity. In fact, a 2011 study32 revealed that the worse one’s insulin resistance is, the greater amount of chromium they excrete in their urine, further compounding its low circulation. It was shown that this chromium dumping occurs well before development of T2DM, and supplementation with the nutrient could prevent its further progression.

 

Furthermore, a 2013 study33 was performed on women with polycystic ovarian syndrome (PCOS) comparing the effects of chromium picolinate and Metformin, a pharmaceutical used to increase insulin sensitivity. After three months of treatment, chromium picolinate significantly decreased fasting blood sugar along with fasting insulin levels, thus revealing increased insulin sensitivity. Chromium was also better tolerated than the Metformin.

 

I agree that supplementation is not a magic bullet, but it could certainly boost metabolic pathways and is a clinically proven beneficial adjunct to a comprehensive treatment plan.

 

Refreshingly, Lustig dedicates 42 pages at the end of the book to public health policy, government, and political involvement in our food supply and their onus in our current mess. He discusses the health insurance industry and the need for sugar intake to be treated the same way smoking was or else we will not be successful in overcoming this health crisis. This was extremely encouraging to hear from an esteemed medical doctor, as most seem to avoid these hot button topics all together.

 

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As a practitioner, I would not recommend this book for all of my clients; it was extremely enjoyable for me because I am familiar with anatomy, physiology, and advanced biochemistry. For the client who comes in who has no clue about anything and just wants to lose weight, this would be way over their heads. However, I would definitely recommend this for “technical” personality types. Clients who inquire about details and scientific research, ask why and how about everything, and who need to see facts and understand things in order to initiate behavior would benefit immensely from Lustig’s explanations. For anyone I recommend this book to, however, I would tell them to skip over the dietary recommendations section. Or, I would need to feel confident in their understanding of my beliefs on food quality and nutrition prior to them reading it.

 

The best part of the book, in my opinion, is Lustig’s tone. He manages to get heavy and difficult messages across to the reader, but keeps things light and provides hope and a means to change things for the better – for everyone – not just for oneself. After all, he stresses that this is not about personal responsibility anymore; it is a public health crisis. He also has a whip-sharp wit and sarcasm, which surprised me for a San Franciscan. It all made sense, though, when I researched his biography; he’s from Brooklyn. 🙂

 

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Enjoy the holiday weekend! Thanks for reading!

 

 

References

  1. Lustig RH, Greenway F, Velasquez-Mieyer P, et al. A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion. International Journal of Obesity. 2005;30(2):331-341.
  2. Keys A, Aravanis C. Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease. Cambridge, Mass: Harvard University Press; 1980.
  3. Yudkin J. Pure, White and Deadly: How Sugar Is Killing Us and What We Can Do to Stop It. London: Davis-Poynter; 1972.
  4. Lustig RH. Pediatric Endocrine Disorders of Energy Balance. Reviews in Endocrine and Metabolic Disorders. 2005;6(4):245-260.
  5. Flier JS. What’s in a Name? In Search of Leptin’s Physiologic Role. Journal of Clinical Endocrinology & Metabolism. 1998;83(5):1407-1413.
  6. Leibel RL. The Role of Leptin in the Control of Body Weight. Nutrition Reviews. 2002;60(10):15-19.
  7. Lustig RH. Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the First Law of Thermodynamics. Nature Clinical Practice Endocrinology & Metabolism. 2006;2(8):447-458.
  8. Leibel RL. Changes in Energy Expenditure Resulting from Altered Body Weight. New England Journal of Medicine. 1995;333(6):399-399.
  9. Lustig RH. Fructose: Metabolic, Hedonic, and Societal Parallels with Ethanol. Journal of the American Dietetic Association. 2010;110(9):1307-1321.
  10. Tetri LH, Basaranoglu M, Brunt EM, Yerian LM, Neuschwander-Tetri BA. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. AJP: Gastrointestinal and Liver Physiology. 2008;295(5).
  11. Post RE, Mainous AG, King DE, Simpson KN. Dietary Fiber for the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis. The Journal of the American Board of Family Medicine. 2012;25(1):16-23.
  12. Levine R. Monosaccharides in Health and Disease. Annual Review of Nutrition. 1986;6(1):211-224.
  13. Carr K., Tsimberg Y, Berman Y, Yamamoto N. Evidence of increased dopamine receptor signaling in food-restricted rats. Neuroscience. 2003;119(4):1157-1167.
  14. Farooqi IS, Bullmore E, Keogh J, Gillard J, O’Rahilly S, Fletcher PC. Leptin Regulates Striatal Regions and Human Eating Behavior. Science. 2007;317(5843):1355-1355.
  15. Carvelli L, Morón JA, Kahlig KM, et al. PI 3-kinase regulation of dopamine uptake. Journal of Neurochemistry. 2002;81(4):859-869.
  16. Little JP, Safdar A, Benton CR, Wright DC. Skeletal muscle and beyond: the role of exercise as a mediator of systemic mitochondrial biogenesis. Applied Physiology, Nutrition, and Metabolism. 2011;36(5):598-607.
  17. Bajpeyi S, Tanner CJ, Slentz CA, et al. Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation. Journal of Applied Physiology. 2009;106(4):1079-1085.
  18. Das UN. Sucrose, fructose, glucose, and their link to metabolic syndrome and cancer. Nutrition. 2015;31(1):249-257.
  19. Kelishadi R, Mansourian M, Heidari-Beni M. Association of fructose consumption and components of metabolic syndrome in human studies: A systematic review and meta-analysis. Nutrition. 2014;30(5):503-510.
  20. Shapiro A, Mu W, Roncal C, Cheng K-Y, Johnson RJ, Scarpace PJ. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. AJP: Regulatory, Integrative and Comparative Physiology. 2008;295(5).
  21. Amin F, Gilani AH. Fiber-free white flour with fructose offers a better model of metabolic syndrome. Lipids in Health and Disease. 2013;12(1).
  22. Sun K, Ren M, Liu D, Wang C, Yang C, Yan L. Alcohol consumption and risk of metabolic syndrome: A meta-analysis of prospective studies. Clinical Nutrition. 2014;33(4):596-602.
  23. Chen C-C, Lin W-Y, Li C-I, et al. The association of alcohol consumption with metabolic syndrome and its individual components: the Taichung community health study. Nutrition Research. 2012;32(1):24-29.
  24. Earnest CP, Johannsen NM, Swift DL, et al. Aerobic and Strength Training in Concomitant Metabolic Syndrome and Type 2 Diabetes. Medicine & Science in Sports & Exercise. 2014;46(7):1293-1301.
  25. Whisman MA, Uebelacker LA. A longitudinal investigation of marital adjustment as a risk factor for metabolic syndrome. Health Psychology. 2012;31(1):80-86.
  26. Swithers SE, Davidson TL. A role for sweet taste: Calorie predictive relations in energy regulation by rats. Behavioral Neuroscience. 2008;122(1):161-173
  27. Newgard CB, An J, Bain JR, et al. A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance. Cell Metabolism. 2009;9(4):311-326.
  28. Lord RS, Bralley A. Laboratory Evaluations for Integrative and Functional Medicine. Revised 2nd Edition. Duluth, GA: Genova Diagnostics; 2012.
  29. Adams SH. Emerging Perspectives on Essential Amino Acid Metabolism in Obesity and the Insulin-Resistant State. Advances in Nutrition. 2011;2(6):445-456.
  30. Korte MS, Koolhaas JM, Wingfield JC, McEwen BS. The Darwinian concept of stress: benefits of allostasis and costs of allostatic load and the trade-offs in health and disease. Neuroscience & Biobehavioral Reviews. 2005;29(1):3-38.
  31. Macotela Y, Emanuelli B, Bång AM, et al. Dietary Leucine – An Environmental Modifier of Insulin Resistance Acting on Multiple Levels of Metabolism. PLoS ONE. 2011;6(6):1-13.
  32. Bahijri SM, Alissa EM. Increased insulin resistance is associated with increased urinary excretion of chromium in non-diabetic, normotensive Saudi adults. Journal of Clinical Biochemistry and Nutrition. 2011;49(3):164-168.
  33. Amooee S, Parsanezhad ME, Shirazi MR, Alborzi S, Samsami A. Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOS: A double-blind randomized clinical trial. Iran J Reprod Med. 2013;11(8):611-618.

 

Depression and Vitamin Therapy??

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Based upon the title of this post and my disappearance from my writing and social life for the past couple of months, you may have your suspicions of a possible immersion in Scientology or striking up an acquaintance with Tom Cruise. Rest assured – this is not the case. While Tom Cruise once notoriously claimed that Brooke Shields’ postpartum depression could be cured by vitamins, I am here solely to enlighten and inform you of an extremely interesting take on an alternative treatment for depression I learned about in my Vitamins & Minerals course this semester….and to break down how it works.

 

Depression is a topic and condition that is close to my heart. Both close friends and family have struggled with mental illness at various times. Having always felt helpless in pulling them out of a spiral, it provided me with some solace in understanding how I might eventually be able to provide them relief through a scientifically-targeted and natural approach. Specifically, through nicotinamide, or niacin supplementation.

 

Depression, like many things in life and particularly health, is multifaceted.

 

There is not just one thing that causes it nor one thing that fixes it. In many cases, too, it’s a game of chicken-or-the-egg: Could depression and stress have triggered one’s physical symptoms, or would someone’s physical pains, diagnoses, and limitations have caused them to become anxious and depressed? The answer is, well, both. Further, they perpetuate each other. What a mess!

 

I’m sure most of you are familiar with or have heard of the neurotransmitter serotonin; its implication in depression and mood disorders is ubiquitous. In fact, anti-depressants classified as SSRIs (selective serotonin reuptake inhibitors) are designed to allow for a higher level of the neurotransmitter to continually circulate, which chemically enhances one’s mood as a result.

 

So, in getting at the root of this serotonin issue, let’s take a look at its biochemical pathway, shall we?

 

tryptophan pathway

 

Serotonin is derived from the amino acid tryptophan, which is found in many foods – most popularly in what we eat on Thanksgiving. Tryptophan has two main fates in our body: it is a constituent of many proteins needed for various enzymes, and it is a substrate for two very important biosynthetic pathways. One of these pathways generates serotonin and the other is called the kynurenine pathway. The kynurenine pathway’s end result is the production of niacin, or vitamin B3, and nicotinamide adenine dinucleotides, which are integral in energy production. In a healthy individual, the funneling of tryptophan into these two pathways and also into protein production is nicely balanced. When one is inflamed, however, protein production and the serotonin pathway are greatly slowed down, and the majority of tryptophan is shunted to and degraded in the kynurenine pathway.

 

The reason for this is an adaptive, protective measure in response to an invading threat, which of course is always our body’s first intent when initiating any sort of inflammation. When pathogens (bacteria, viruses, etc.) enter the body, they feed on protein to grow and proliferate. In order to starve these bugs so the threat subsides, this inflammatory response hides tryptophan and places it in the kynurenine pathway. Smart, right? Yes.

 

However, when inflammation is prolonged, which is the case in all chronic illness, a sustained predominance of the kynurenine pathway leads to some negative repercussions. One of which is insufficiency of serotonin, which contributes to depression. And, since serotonin is a precursor for the production of melatonin, sleep disturbances soon ensue from lack thereof.

 

kynurenine pic

The Kynurenine Pathway

 

While this state of imbalance results in an insufficiency of serotonin, at the same time it produces an excess of certain kynurenine metabolites. If you look at the pathway above, you will see something called quinolate towards the end, which is a potent neurotoxin. Quinolate’s accumulation is often the reason we experience pain during viral infections, such as the flu. It’s also a reason why (cue the Cymbalta commercial) depression hurts. Quinolate also interacts with receptors in the brain that respond to pain, and, with too much of it circulating around, its excitatory stimulus can cause degeneration of neurons in the brain leading to loss of function. Such toxicity has been shown to be the case in stroke, Alzheimer’s, and dementia.

 

Ok, so where does niacin come in, you’re wondering?

 

Well, if you look at the pathway once more, you will see that the last stop on the kynurenine train is nicotinic acid (niacin, in other words). The whole enzymatic pathway functions as a negative feedback loop. For instance, say you had a hunger signal coming from your brain and your stomach is growling…this makes you want to eat and go searching for food, right? Once you’re full and satiated, this sends a negative feedback signal to your brain that says, “okay, you’re full, you no longer need to eat.” If you’re feeling full most of the time, you won’t be compelled to reach for the refrigerator. Similarly, if you supplement with nicotinamide (a form of niacin that doesn’t make your skin flush), this sends a negative feedback signal to the enzyme in charge of initiating the tryptophan steal into this pathway in the first place (IDO/TDO), and says, “well we have the end product we need in abundance, we really don’t need to move all the tryptophan into here anymore.” So, the enzyme turns off, tryptophan is no longer being sucked in there, and it becomes more available for its other pathway, and converts to serotonin. With more serotonin being synthesized, one’s depression essentially improves. I told you it was interesting.

 

Further, quinolinate production would consequently be reduced, giving your brain a break from all the toxic stimuli. In fact, a study on patients with HIV infection treated with nicotinamide increased plasma tryptophan concentration by 40%, without major side effects that are commonly seen with the administration of anti-depressants. It accomplished this by suppressing the enzyme activity that initiates the kynurenine pathway.

 

Obviously, this is by no means a cure-all for depression.

 

As I mentioned before, the reason why this metabolic detour occurs in the first place is because one is inflamed. Then it can initiate depression, which makes you more inflamed and even more depressed. Supplementation of niacin works by rewiring this vicious cycle while you address the main sources of inflammation to stop the detour from happening at the start.

 

There are many etiological factors of inflammation, which I plan to address in a future post on the allostatic load model. One of these is, of course, our many negative thoughts and feelings we have as a result of deep-rooted emotional patterns and daily struggles we experience in life. Psychotherapy is an essential tool in helping to reduce some of these loads. Where I or some other functional medicine practitioners would come in is to address the inflammation from all other angles in order to keep one afloat while they delve into their personal and emotional intricacies. We all have these.

 

On a personal note, I, too, experience bouts of depression related to managing, enduring, and trying to navigate and solve what is truly going on with my health for all of these years. It is a feeling of complete lack of control over my life and future at times where I am constantly treading water in my efforts to maintain being “Erin.” The lines get blurred as to whether my emotions are a result of all of these very stressful factors, or, if it is part of the picture itself. It also becomes an overwhelming undertaking to feel as though I would have to iron out all of my deep-rooted life events in order to become healthier. As I am learning each day, especially from the many downstream effects that inflammation has (specifically on this pathway), it starts to make more sense in knowing there’s a lot more to it than most people think. It’s also comforting to understand that.

 

So, if you or someone close to you suffers with depression or mental illness, it’s important to evaluate the entire health picture.

 

There could be underlying inflammation that could trigger, contribute to, or perpetuate one’s depression. Or, depression could lead to further health issues on its own. I guess I haven’t addressed the chicken-or-the-egg question yet!

 

Seeing a functional doctor or nutritionist, along with a great psychologist could definitely make things, well, a little brighter.

 

Have a great weekend and smile 🙂

 

References:

  1. Schrocksnadel, K.; Wirleitner, B.; Winkler, C.; Fuchs, D. Monitoring tryptophan metabolism in chronic immune activation. Clinica Chimica Acta 2006, 364, 82-90.
  2. Lord, R. S.; Bralley, A. J. Laboratory Evaluations for Integrative and Functional Medicine, Revised 2nd Edition; Genova Diagnostics: Duluth, GA, 2012.