The Top 3 Supplements for Anyone and Everyone, Part II

Ok, so Part I was a bit of a diversion from what was my initial intention, but I hope that you can understand why it had to happen. We need to have a framework, a map, a structure of the big picture in order to inform our choices in the components of the big picture. If we don't have the foundational principles of the big picture in place, we run the risk of missing the forest for the trees. We scream from the mountaintop that this particular essential oil is going to cure everyone's arthritis, insomnia, and cancer, improve your relationship with your mother, and transform your spiritual practice.  

Yes, there are some really important supplements for many of us, but individualization is part of a more comprehensive and effective approach to (Naturopathic) medicine. So, now with the knowledge that the best 3 supplements for you and me may be completely different depending on our specific situations, let's do our best to make a little more sense of things and use a few principles to guide our supplement choices.


Let us review some of the principles, processes, and major systems that are at play when we are trying to prevent, palliate, or cure any chronic 'dis-ease' (this is a non-exhaustive list that I find helpful as a starting point), or promote longevity and wellness to help inform our supplement choices.


Note that the following are heavily focused on the biological plane, as this is more related to my area of training and expertise, but there are definitely other contributors to health and wellness that are more related to the (coexisting) psycho-spiritual and other more subtle aspects of the human experience. I'm sure that they are important, but I will not comment on them beyond mentioning that they exist, as I am not knowledgeable enough to have any authority in these areas.


  1. Inflammation, glycation, and oxidative stress - processes that increase chronic low-grade inflammation, glycation of tissues, and oxidative stress contribute to all chronic diseases, aging, and cancer

  2. Stress and our ability to respond effectively (mental and physical components) needs to find a certain balance. Influenced to some degree by 1. above.

  3. Immune balance (tonification in some cases, decreasing ‘autoimmune’ processes in other cases). Influenced by 1. & 2. above.

  4. Detoxification and elimination - removal of physical toxins made by us, bacteria, or environmental) from our physiological structures improves the effectiveness of our body’s biochemical functions (improving detoxification of cells, tissues, organs, the entire body improves the function of all systems). Influenced by all of the above.

  5. Digestion - the actual breakdown of food, absorption, transport of nutrients, vitamins, minerals. (“All disease begins in the gut” -- Hippocrates). This is fairly self-explanatory and is influenced by all of the above factors.

  6. Microbiome - the 'bugs' inside us are good, bad, or in-between, and we must constantly strive to optimize the diversity and density of ‘bugs’. Possibly the next frontier in medicine and related to all of the above, but most intimately to 5., 4., and 3.

  7. Nervous system biology - as a major part of the physical manifestation of the intelligence that governs the body (the 'Vis'), the nervous system has special importance. Preservation and optimization of the nervous system improves all systems that it governs. The parasympathetic and sympathetic balance are included here and very related to 2. above, in particular, but there is no system or process above that isn't influenced or regulated to a large degree by the nervous system (i.e. the 'Vis').

As we progress in these core principles and processes it becomes more and more evident that there is much overlap and interrelation, so I'll try not to repeat too much.  

The pattern of disease is an expression of the response of man to his total environment (physical, biological, and social); this response is, therefore, determined by anything that affects man himself or his environment.
— Rene Dubos, 1961

1. INFLAMMATION and OXIDATIVE STRESS

 "... significant evidence implicates chronic, low-grade inflammation as one of the most consistent biologic features of both chronological aging and various age-related diseases/disorders" (1). 

disease oxidative stress inflammation.gif

This is the rationale for any intervention that may help decrease chronic inflammation and excessive oxidative stress. Inflammation is not inherently noxious and bad (think of an acute injury that requires the new blood flow and immune cells that are needed for addressing the problem), but it inflammation continues without resolving, we have a problem. 

Glycation contributes to the aging of tissues and can cause increased oxidative stress (25).

Examples of possible interventions to address inflammation and oxidative stress include phytochemical antioxidants and anti-inflammatories. "Intervention" can be interpreted as something as simple as a phytochemical-rich diet (high vegetable and fruit content) or more isolated extracts such as curcumin, quercetin, resveratrol etc.

A few solutions I quite enjoy (in addition to a phytochemical-rich diet) is drinking a herbal tea that suits your condition, constitution, or goals, a 'greens drink', or a daily glass of organic red wine


2. STRESS

This section is largely why there is an R in my NMRx Framework.

Stress can actually be divided into EUSTRESS and DISTRESS. We require some stress to thrive (eustress), but it can get out of hand, beyond our personal ability to cope adequately, and then lead to distress. The autonomic nervous system and the adrenocortical system can protect us in the short term, but can accelerate disease progression and damage when activated for too long.

It sounds a lot like the situation with oxidation/inflammation above, right? 

  McEwen BS . Allostasis and allostatic load: implications for neuropsychopharmacology.  Neuropsychopharmacology.  2000 Feb;22(2):108-24.

McEwen BS. Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology. 2000 Feb;22(2):108-24.

We must react to stressors but maintain homeostasis. Allostasis '(literally “maintaining stability, or homeostasis, through change”) refers to the process of adaptation to acute stress, involving the output of stress hormones which act in the ways described above to restore homeostasis in the face of a challenge' (2)

Allostatic load can become too much and lead to illness through the following:

  • Repeated “hits” from multiple novel stressors
  • Lack of adaptation
  • Prolonged response due to delayed shut down
  • inadequate response that leads to compensatory hyperactivity of other mediators

A good summary of stress management sounds very similar to the serenity prayer. Basically, we control what we can, be proactive in building our resilience and adaptability, while accepting that things will go wrong at some point. 

Some of my favourite ways to address stress include relaxation response-inducing activities (interventions that activate the parasympathetic "rest and digest" response) such as yoga, meditation, tai chi, progressive muscle relaxation and myriad others. Personally, I enjoy meditation.

But what is the best one?

The one you will actually do regularly, proactively, and make it a habit. 

Even 5-10 minutes a day can make a difference.

Other interventions include adrenal support "adaptogens". Although adaptogens do not directly eliminate the stressor or change the perception of the stressor on the nervous system, they may help indirectly by supporting homeostasis or minimizing the damages incurred from an increased allostatic load (i.e. in times where we are stretched beyond our homeostatic parameters). This improved physical resilience may then confer more mental resilience in future stressors etc., leading to an improved ability to deal with similar stressors in the future. 

Adaptogens are very often part of a basic, foundational supplementation strategy. They have a normalizing, strengthening effect on the body and help our bodies deal with the physiological results of stress. There are many adaptogens from various parts of the word; Panax quinquefolius (Canadian/American Ginseng), Panax ginseng (Korean/Asian Ginseng), Withania somnifera (Indian "Ginseng"), Eleutherococcus senticosus (Siberian "Ginseng"), Lepidium meyenii (Maca), and Ocimum tenuiflorum (Indian Tulsi), to name a few. For a good review of supplements including those mentioned above, be sure to check out www.examine.com (3); there may be one that you think is particularly suited to your needs.


3. IMMUNE BALANCE

I may have bitten off more than I can chew by even attempting to address something as intricate and complex as immune balance, so please accept the following as a kind of level 1 introduction.

Our immune system can be 'overactive' in some cases (i.e. allergies, autoimmune diseases), or it can be underactive in some cases (repeated and persistent respiratory or other infections, thrush/candida), and some of the most important influences on immune balance occur via the gut (5). Manipulation of the immune system via nutrition and the microbiome is a cornerstone of a comprehensive approach to immune system homeostasis (balance), although it is well-known that our psychology also has a profound influence on our neuro-immune function, and vice-versa (6). Even laughing can have a beneficial effect on our immune system, decreasing stress and increasing our Natural Killer cell activity, which confers increased resistance to disease and morbidity in those with cancer and HIV (7). 

Essentially, we have a lot of controllable factors when it comes to immune balance, including (but not limited to) the following:

  1. mindset and psychology (cognitive behavioural interventions, laughing etc.)
  2. diet/nutrition
  3. microbiome (highly related to 2. above)

Generally a 'good' mindset and psychological state will support a healthy gut structure (and function), as will a 'good' diet. Additionally, a good diet will support a healthy microbiome. 

So let us start with food.

If you have the drive and commitment to make some changes, diet is a great place to start, and it will lead to benefits in the mental-emotional realm as well as influence our immune system homeostasis. (If psychological factors such as low commitment, drive, and vision are so prohibitively low that one cannot even start, let alone stick to a healthy diet regimen, perhaps more external support is needed. This may include psychological-focused interventions, stress management, social and/or professional support etc., to name a few).

Trends Neurosci. 2016 Nov;39(11):763-781. doi: 10.1016/j.tins.2016.09.002. Epub 2016 Oct 25.

From a supplement perspective, one of the first things I consider is a probiotic. It is a safe and easy intervention that can positively impact the gut and microbiota directly, with possible benefits bestowed upon our psychology via the principles of psychoneuroimmunology. The probiotics with anxiolytic and/or anti-depressant action (called psychobiotics) are a great example of applying the concepts of psychoneuroimmunology via manipulation of gut flora. Probiotics work in one of the following ways:

 

Another possible intervention to help with immune balance would be vitamin D, which has a modulating effect on the immune system. Vitamin D supplementation can increase resistance to infections of the respiratory tract (9), and deficiency of vitamin D is associated with increased incidence of autoimmune disease (10). 


4. DETOXIFICATION AND ELIMINATION

Detoxification is often interpreted differently by different people; this Metagenics blog post is a good primer for those who are just getting into the subject.

Naturopathic Doctors have talked about the concept of dysbiosis and endotoxemia for quite some time (11), but even then, it wasn't a new idea; endotoxemia was discussed by ancient Egyptian and Greek physicians (20).

Basically, detoxification involves the removal of noxious (toxic) chemicals such as ammonia, urea, uric acid, carbon dioxide, xenobiotics, endotoxins, mycotoxins, drugs, etc. from the body. These toxins can be derived from normal cellular processes (e.g. when we make ATP via oxidative phosphorylation or metabolize proteins and produce ammonia), metabolism of bacteria in the gut (11), or ingestion/inhalation/absorption of processed foods or man-made chemicals (xenobiotics) etc. Regardless of their origin, toxins compromise health and can contribute to various disease processes (12). Luckily, our bodies are equipped with mechanisms to remove them.

 Overview of metabolic detoxification processes.

Overview of metabolic detoxification processes.

There are several organs in the body that are important for detoxification and elimination, including the kidneys, lungs, liver, and skin. That is why Naturopathic doctors will often look to support your organs of detoxification in order to benefit the overall function of the body; most commonly, this will involve liver and colon (gut) supporting nutritional, phytochemical/herbal, or other therapies such as Biotherapeutic Drainage, sauna (13) to name a few.

There are many ways to encourage detoxification, and it will likely come as no surprise that food is where I generally start. If someone is eating North American wheat products or excessive carbohydrates that feed the 'nasty' bugs in our guts, or they have insufficient stomach acid and leaky gut leading to excess formation and absorption of toxic metabolites into the body, or a SAD diet is so low in vitamins and cofactors that are necessary for Phase I or Phase II detoxification reactions, or they only have one bowel movement per week, or they drink 8 beers a night, they will benefit from improved detoxification and elimination by an improvement in diet and nutrition. 

There are many different diets to implement, but I find that the Institute for Functional Medicine's Elimination Diet is one of the very best.

With regards to supplementation, it depends on whether your urinary and GI system are functioning well. If you're constipated, fix that first; there is no point in mobilizing toxins if there is nowhere for them to go. If colon and kidney function are adequate, then a supplement that supports liver function is one of the best supplement strategies to consider. I use one in my practice that includes milk thistle and other phytotherapeutics as well as nutritional cofactors of Phase I and Phase II detoxification processes.

However, lately I have been turning more and more to the use of Biotherapeutic Drainage, a very gentle, safe, and extremely effective starting point. Here is an example of a Biotherapeutic Drainage product that is widely available in Canada.


5. DIGESTION

Digestion influences many of the above mentioned principles/processes:

  • oxidative stress (e.g. overeating) and inflammation (ingestion of inflammatory omega 6 fatty acids)
  • stress compromises blood flow to the digestive apparatus (e.g. stress-induced ulcer)
  • immune balance is influenced by improper digestion and a leaky gut
  • digestion has a direct effect on toxin production (e.g. breakdown of proteins leading to ammonia etc.) and the digestive apparatus is a key route of elimination 

The various processes are interconnected.


Optimizing digestion via nutrition has been a theme of the above, but beyond 'clean eating', lets discuss a couple of basic fundamental aspects that we can address. Improvements in any of the following aspects of digestion can be extremely helpful:

  • salivation
  • chewing
  • proper acid secretion and storage (i.e. keeping that acid where it is supposed to be)
  • maintenance of the structures of the gut (ie. barrier of the gut, function of sphincters and valves)
  • hormone, enzyme, bicarbonate secretion
  • motility (propulsion of gut contents)
  • microbiota composition (i.e. fewer pathogenic microorganisms)
  • elimination and detoxification functions
 Source: http://defenderauto.info/digestive-system-organs/

Source: http://defenderauto.info/digestive-system-organs/

Salivation - cooking your food increases salivation and gets the engine running more than driving to the pick-up window and McDonalds.

Chewing - digestion is the breakdown from large to small 'pieces', via physical (chewing starts it off), chemical (acid breakdown in the stomach), enzymes (e.g. pancreatic lipase to help break down fats). This is a linear process, so simply chewing more can have a huge impact on your ability to break things down and digest properly.

Stomach acid - insufficient stomach acid (largely unrecognized in the conventional medical community; this may be related to the popularity of acid-suppressing medications that are very commonly prescribed) not only leads to improper breakdown of food as it descends in the gut and possibly contributes to food allergy (14), it also leaves us more susceptible to small intestinal bacterial overgrowth (SIBO) and other GI infections (15). 

All disease begins in the gut.
— Hippocrates

Structure of the gut - the gut should keep some things out, and let some things in. When bacteria or their products are absorbed into the system it can result in damaging inflammation and immune activation. The sphincter that keeps acid in the stomach from rising into the esophagus is central to how GERD (reflux disease) develops.

Enzymes - these are specialized to break down various fats (e.g. lipase), carbohydrates (e.g. amylase), or proteins (proteases eg. trypsin). The contents of the gut have been chewed (physical breakdown), exposed to acid in the stomach (chemical breakdown), and the digestive enzymes continue this process so that we can properly absorb nutrients, vitamins, and minerals. As we age our output of digestive enzymes and bicarbonate decreases (16) (as does our stomach acid). 

Motility - the muscles of gut have nerves that control them; if the neuromuscular units are not working properly, things don't keep moving downward in the gut. This can lead to motility disorders such as gastroparesis and contribute to the development and maintenance of SIBO.

The microbiota will be discussed below (6.) 

Detoxification has been discussed above, but it is worth mentioning that there the capacity of colonocytes (cells in the colon) to carry out detoxification or transformation of chemicals is equal to that of hepatocytes (19), the cells of the liver. If the detoxification activity of colonocytes can be considered a 'micro' level detoxification of chemicals and compounds, the elimination of stool from the colon may be considered the 'macro' level correlate, and it is critical to the healthy functioning of the body to rid the body of these macro wastes. Although I will not discuss it beyond mentioning it here, it is important to realize that ideal elimination should not involve the excessive loss of water, nutrients, vitamins, minerals etc. (i.e. don't throw the baby out with the bathwater).

6. THE MICROBIOME

"The human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut; the human microbiome consists of the genes these cells harbor" (20). The study of the microbiome is one of the new frontiers in health and medicine, but even the inventor of the first microscope, Antonie van Leewenhoek, was comparing his oral and fecal microbiota as early as the 1680s.

Probiotics mechanism .png

We are exposed to 100 times more genetic material from microbes than our own, so it is hardly surprising that imbalances in the microbiota have far reaching consequences for our health. 

Liang and FitzGerald's 2017 paper (17) states 'Dysbiosis has been linked to malnutrition, ulcerative colitis, neurological disorders, autoimmune diseases, hypertension, thrombosis and atherosclerosis, and cancer'. 

It is likely that the above list will continue to grow as the research continues to find new links.

Gone are the days of the overly simplistic notion that all bacteria are bad, and it is us against the bacteria. We humans are part of a superorganism, a 'communal group of human and microbial cells all working for the benefit of the collective' (21) that coexists (and co-evolved) with the microbes that make our bodies their home. When we aim for total health for us, we must shift our thinking to include this superorganism concept; what is good for the whole, is good for us. The composition of our microbiome results from some controllable factors such as diet, duration of breastfeeding, food introductions, as well as uncontrollable factors such as method of delivery (18) and geographic location.

So, where do we start when we're trying to optimize our microbiome?

Again, we start with food.

In my practice I try to convey to my patients that when we eat, we are not eating alone; we're feeding our microbiome. We need to choose foods that benefit us and the best version of our microbiota. The microbiota have to adapt to the food that we decide to eat, and we have the power to make better choices. Essentially, 'bad' foods support the growth of 'bad' bugs; however, it is a little more complex in practice due to interindividual differences (immune system, microbiome etc.).

One of the first things to consider is a sustainable therapeutic diet upgrade. In some cases it may be helpful to include more fibre and prebiotics (food for probiotics), probiotics, fermented foods (22) such as kefir and kimchi. In some cases antimicrobial herbs may be indicated, but that is beyond the intended scope of the present information.


7. NERVOUS SYSTEM BIOLOGY

The biology of the nervous system is necessary to the functioning of all the systems and processes above. Below are examples of how each of the above (1.-6.) can be related to the nervous system:

  1. Oxidation + Inflammation - those who suffer from depression are inflamed (23).
  2. Stress - the relationship is straightforward. The subjective perception of stress requires the nervous system.
  3. Immune Balance - as discussed above, our understanding of the field of psychoneuroimmunology has linked our psychology and associated nervous system biology to our immune system function.
  4. Detoxification + Elimination - 'mad as a hatter'; accumulation + insufficient elimination/detoxification of mercury can lead to neurotoxicity and psychological symptoms (24).
  5. Digestion - the digestive system has its own enteric nervous system, and there is a bidirectional 'gut-brain axis'. An example of this relationship would be the kind of diarrhea that one may experience before a test (personal experience).
  6. Microbiome - bacteria within the gut can produce the same neurotransmitters that our central nervous system uses. This stretches the 'gut-brain' axis to become the 'gut-brain-microbiome' axis.
An alternative philosophy of life is needed, where every change starts with the individual person, meaning that a sick person is able to do much more for him or herself than any physician. A lonely person can do more for himself than any psychologist. A person with sexual problems can help himself to a greater extent than any sexual therapist.
— Ventegodt S, Andersen NJ, Merrick J. Quality of life philosophy I. Quality of life, happiness, and meaning in life. Scientific World Journal. 2003 Dec 1;3:1164-75.

There are non-supplement interventions that I will often turn to when trying to optimize a patient's nervous system, including counselling, meditation or other mindfulness techniques, homeopathy, or acupuncture, for instance. Psychological health is not possible without nervous system biology, and interventions that improve our psychological health and wellbeing will benefit the nervous system. I find it important to discuss what one's purpose is; or, what in their life gives them a sense of meaning? This is related to the 'x' in my NMRx Framework discussed previously in Part I or in my interview with Robert Macleod, and it has a large impact on the biology of the nervous system. I would include sleep and stress management (discussed above) as important factors that contribute to a healthy nervous system.

However, in order to keep with the original intention of informing our supplement choices with some foundational principles, I would suggest that among my favourite supplements for the nervous system is a high quality source of omega-3 fatty acids; I use krill oil and fish oil in clinical practice. There is much debate about which one is superior, but the intention of this post was not to split hairs about specific supplements; it was to make sure that we have the big picture in mind, help inform our specific choices with and understanding of the various principles at work. In other words, assuming you eat an average 'Western' diet, taking fish or krill oil will do your nervous system more good than not taking any of either.


Here is a list of some of the most common prescriptions or plans I use during the first couple of visits, depending on the patient's state of health and their motivation/commitment etc.

  • low carbohydrate, whole foods based diet with no limitations on vegetables and fruits (other than bananas)
  • probiotics
  • digestive bitters, betaine HCl, apple cider vinegar, or digestive enzymes 
  • NMRx worksheet
  • biotherapeutic drainage kit for either stress/insomnia or kidney/liver detoxification 
  • magnesium citrate if constipated
  • adrenal support if highly stressed and signs of adrenal fatigue

There are numerous other interventions that may be indicated, but the above includes some of the most common ones that I use very frequently.


If you're still reading, thank you; I appreciate you taking the time to try and understand what I'm trying to share from my experience as a Naturopathic Doctor.


 

REFERENCES:

  1. Buford, Thomas W. “(Dis)Trust Your Gut: The Gut Microbiome in Age-Related Inflammation, Health, and Disease.” Microbiome 5 (2017): 80. PMC. Web. 26 Feb. 2018. 

  2. McEwen BS. Allostasis and allostatic load: implications for neuropsychopharmacology.  Neuropsychopharmacology. 2000 Feb;22(2):108-24. Review.

  3. www.examine.com

  4. Wu H-J, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012;3(1):4-14. doi:10.4161/gmic.19320. 

  5. Dinan TG, Cryan JF. Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome. Neuropsychopharmacology. 2017;42(1):178-192. doi:10.1038/npp.2016.103.

  6. Dinan TG, Cryan JF. Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome. Neuropsychopharmacology. 2017;42(1):178-192. doi:10.1038/npp.2016.103.

  7. Bennett MP, Lengacher C. Humor and Laughter May Influence Health IV. Humor and Immune Function. Evidence-based Complementary and Alternative Medicine : eCAM. 2009;6(2):159-164. doi:10.1093/ecam/nem149.

  8. Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PWJ. Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals. Trends in Neurosciences. 2016;39(11):763-781. doi:10.1016/j.tins.2016.09.002.

  9. Bergman P, Lindh ÅU, Björkhem-Bergman L, Lindh JD. Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Gluud LL, ed. PLoS ONE. 2013;8(6):e65835. doi:10.1371/journal.pone.0065835.

  10. Prietl B et al. Vitamin D supplementation and regulatory T cells in apparently healthy subjects: vitamin D treatment for autoimmune diseases? Isr Med Assoc J. 2010 Mar;12(3):136-9.

  11. Pizzorno J. Toxins From the Gut. Integrative Medicine: A Clinician’s Journal. 2014;13(6):8-11.

  12. Crinnion WJ. Environmental medicine, part one: the human burden of environmental toxins and their common health effects. Altern Med Rev. 2000 Feb;5(1):52-63.

  13. Crinnion W. Components of practical clinical detox programs--sauna as a therapeutic tool. Altern Ther Health Med. 2007 Mar-Apr;13(2):S154-6. 

  14. Untersmayr, Eva et al.Antacid medication inhibits digestion of dietary proteins and causes food allergy Journal of Allergy and Clinical Immunology, Volume 112, Issue 3, 616-623.

  15. WILLIAMS, C. and McCOLL, K. E. L. (2006), Review article: proton pump inhibitors and bacterial overgrowth. Alimentary Pharmacology & Therapeutics, 23: 3–10. doi:10.1111/j.1365-2036.2006.02707.x

  16. Rémond D, Shahar DR, Gille D, et al. Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition. Oncotarget. 2015;6(16):13858-13898.

  17. Liang X, FitzGerald GA. Timing the Microbes: The Circadian Rhythm of the Gut Microbiome. J Biol Rhythms. 2017 Dec;32(6):505-515. doi: 10.1177/0748730417729066. Epub 2017 Sep 1.

  18. Munyaka PM, Khafipour E, Ghia J-E. External Influence of Early Childhood Establishment of Gut Microbiota and Subsequent Health Implications. Frontiers in Pediatrics. 2014;2:109. doi:10.3389/fped.2014.00109.

  19. Roediger WE, Babidge W. Human colonocyte detoxification. Gut. 1997 Dec;41(6):731-4.

  20. Seaman DR. Toxins, Toxicity, and Endotoxemia: A Historical and Clinical Perspective for Chiropractors. Journal of Chiropractic Humanities. 2016;23(1):68-76. doi:10.1016/j.echu.2016.07.003.

  21. Sleator RD. The human superorganism - of microbes and men. Med Hypotheses. 2010 Feb;74(2):214-5. doi: 10.1016/j.mehy.2009.08.047. [Abstract only]

  22. Selhub EM, Logan AC, Bested AC. Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. Journal of Physiological Anthropology. 2014;33(1):2. doi:10.1186/1880-6805-33-2.

  23. Han Q-Q, Yu J. Inflammation: a mechanism of depression? Neuroscience Bulletin. 2014;30(3):515-523. doi:10.1007/s12264-013-1439-3.

  24. Dumont MP. Psychotoxicology: the return of the mad hatter. Soc Sci Med. 1989;29(9):1077-82. [Abstract only]

  25. Gkogkolou P, Böhm M. Advanced glycation end products: Key players in skin aging? Dermato-endocrinology. 2012;4(3):259-270. doi:10.4161/derm.22028.

  26. Ventegodt S, Andersen NJ, Merrick J. Quality of life philosophy I. Quality of life, happiness, and meaning in life. Scientific World Journal. 2003 Dec 1;3:1164-75.

There is nothing in the world, I venture to say, that would so effectively help one to survive even the worst conditions as the knowledge that there is a meaning in one’s life.
— Viktor Frankl