Notice: Any books purchased from Wed. May 30 through Sat. June 2 will be shipped on Monday June 4th. We are sorry for this inconvenience.
Cardiometabolic Road map coming This Spring!
Many of you have been asking us “When is the next Road map going to be ready” and we can now tell you that our target is to have it ready to ship this spring (2018). As you can imagine if you have read any of our previous Road maps, the amount of relevant information published in the cardiometabolic field is probably more than any other, and the number of lifestyle and nutrient-related remedies that have been investigated is vast. …All of which means that we are sifting through mounds of information to bring you the sort of informed, balanced and evidence-based approach that we have taken with each of our other projects (though this one is slated to be a bit larger than the previous GI book). We realize that this has taken longer than we (or you) would have liked, but in addition to the tremendous breadth of this topic (and due to the publication of the previous books), Dr. Guilliams has had additional speaking and writing requests over the past year that were unanticipated. We want to thank you for your patience and hope not to rely upon it much longer. We will let all of you know when we are ready to take pre-orders for the new book and maybe provide a sneak peak of a portion in the very near future. Stay warm, spring is just around the corner.
We have recently posted a new whitepaper that outlines our continued concern over the current use of Red Yeast Rice supplements by clinicians. As our whitepaper details, these products are not reliably effective and many are of dubious legal status. If you use or recommend RYR products, please read the entire whitepaper to see this important information
Dr. Guilliams was recently interviewed by Dr. Hoffman for his “Intelligent Medicine” podcast. Dr. Hoffman was given an early version of Dr. Guilliams’ new book “Functional Strategies for the Management of Gastrointestinal Disorders,” much of which was touched upon in this fast-paced and wide-ranging interview. You can listen to the podcast (in two segments) here: Part 1 and Part 2.
For a visual sneak peak of the book (and to take advantage of our pre-shipping sale through November 2016, check out the GI book page.
Artificial sweeteners such as aspartame (NutraSweet®, Equal®), sucralose (Splenda®), and saccharin (Sweet’N Low®) are ubiquitous in processed foods and beverages; and are regularly consumed by 1/3 of all Americans in a variety of “diet” products.[i] While designed to be low calorie alternatives to sugar, research has repeatedly shown that consumption of these artificial sweeteners is still linked to metabolic derangements such as weight gain, impaired glucose tolerance and increased incidence of type 2 diabetes.[ii],[iii] Now, research has discovered that while most of these synthetic sweeteners are excreted unchanged in either the urine or feces, they affect metabolism through alterations of the gut microbiota.
In an animal model, Suez et al. showed aspartame, sucralose and saccharin induced glucose intolerance over eight and eleven weeks; further study of saccharin demonstrated the effects were mediated through compositional and functional changes to the gut microbiota, with more than 40 operational taxonomic units altered in the saccharin-fed group.[iv] Interestingly, Akkermansia muciniphila was underrepresented in the mice fed saccharin. Using antibiotics and transplanting fecal microbiota samples into germ-free mice, the group linked the impaired glucose tolerance to an altered microbiome.
The group then studied the effects of artificial sweeteners in a small-scale human intervention study. Seven subjects (who did not normally consume artificial sweeteners) consumed a regular diet supplemented with the upper limit of daily saccharin dose (5 mg/kg/day) for one week. Four of the seven volunteers showed an elevated glycemic response (responders), and the other three individuals showed no response. The researchers transplanted the four responders’ microbiota into germ-free mice and replicated the impaired glucose response, again linking the metabolic effects to the altered microbiota. The responder/non-responder effect suggests that not all individuals are affected equally by artificial sweetener consumption, and the response may depend on an individual’s baseline microbiota.[v] Although this is one of the few human intervention trials available to show the effect of artificial sweeteners on the microbiome, other animal studies using these ingredients (at relevant dietary doses) suggests that this phenomena is an important link between artificial sweeteners and metabolic dysregulation.[vi],[vii]
Ironically, many “light” yogurt products include these artificial sweeteners as a key ingredient in the effort to retain palatability while reducing total sugars and calories. Consuming yogurt products in an effort to favorably modify the microbiome while consuming these “light” or “reduced calorie” additives may detrimentally undermine any beneficial changes to the microbiome the consumer anticipates.
[This is a short excerpt from the “Supporting the Microbial Ecosystem of the Gut” section of our newest Road map Functional Strategies for the Management of Gastrointestinal Disorders, which is now (finally) ready to be ordered.]
[i] Sylvetsky AC, Welsh JA, Brown RJ, Vos MB. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr. 2012 Sep;96(3):640-6.
[ii] Suez J, Korem T, Zilberman-Schapira G, et al. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes. 2015;6(2):149-55.
[iii] Spencer M, Gupta A, Dam LV, et al. Artificial Sweeteners: A Systematic Review and Primer for Gastroenterologists. J Neurogastroenterol Motil. 2016 Apr 30;22(2):168-80.
[iv] Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6.
[v] Nettleton JE, Reimer RA, Shearer J. Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance? Physiol Behav. 2016 Apr 15. pii: S0031-9384(16)30164-0.
[vi] Palmnäs MS, Cowan TE, Bomhof MR, et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLoS One. 2014 Oct 14;9(10):e109841.
[vii] Abou-Donia MB1, El-Masry EM, Abdel-Rahman AA, et al. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-29.
The Newest Road map- is finished and ready to ship now! For those who have been waiting, you can now order the book and get them sent to you “hot off the presses.” This 250 page volume is twice the size of each of the last two Road maps and covers basic principles of core GI function as well as specific protocol suggestions for important chronic GI conditions (IBD, IBS, SIBO, H. pylori, AAD, C. diff., Candida and more). The book will retail for $49.95, but is available this month only (November 2016) for $39.95. Remember- this includes free shipping in the United States. We also offer expedited shipping for a small additional cost and also have International Shipping options available for a reasonable rate.
You won’t be disappointed, Dr. Guilliams and his team really took this one to the next level with over 65 figures and tables, including nearly 1,500 relevant and updated references for further study.
Check out the excerpt in the Product page below.
For all those interested in purchasing our books from outside the United States, we now have added two shipping options, one for Canada and another for most everywhere else. You will see these options at the checkout portion of the shopping cart as shipping options. We have set prices only for 1 or 2 books (which are the same price). If you would like to purchase more than 2 books or have additional questions, please email us at email@example.com
Ebook versions are NOT yet available.
Our last Standard publication focusing on Nutrition and Supplementation during pregnancy is now available for download in our Resource Section. Prenatal Nutrition: The Role of Diet and Supplementation (Vol. 11 no 1). A review covering the unique dietary needs and recommendations for pregnant (or soon to be pregnant) women. This covers dietary patterns, macronutrients, vitamins, minerals, key support nutrients and even probiotic recommendations. This discussion covers basic nutrient mechanisms as well as genomic (and epigenetic) influences of nutrients. Also covered are nuances between different forms of supplemental folates, iron and vitamin B12, some of which may be of interest to the clinician making specific recommendations.
You can download your copy here: http://www.pointinstitute.org/the-standard/
Re-assessing the Notion of “Pregnenolone Steal”
When clinicians measure salivary cortisol and DHEA (DHEA-S) to assess stress and HPA axis function, it is common to find DHEA levels below the reference range in a number of individuals. A common explanation for the depletion of DHEA and other hormones (e.g., progesterone, testosterone) due to chronic stress is the phenomenon known as “pregnenolone steal.” This notion basically states that since all steroid hormones use pregnenolone (derived from cholesterol) as a precursor, the elevated secretion of cortisol caused by acute or chronic stress will inevitably result in less available pregnenolone to serve as a precursor for the production of DHEA and other down-stream hormones. In other words, according to this theory, the need for cortisol synthesis “steals” pregnenolone away from other hormone pathways, reducing the potential synthesis and secretion of other necessary hormones, resulting in some of the pathophysiological changes related to stress.
While a rise in cortisol levels and a concomitant drop in DHEA is one of the clinical characteristics of early and mid-stage chronic stress progression, this phenomenon is not caused by diminished adrenal pregnenolone availability or “pregnenolone steal.” The most obvious reason is the fact that the conversion of cholesterol to pregnenolone occurs in the mitochondria of each respective adrenal cortex cell type that is responsible for producing these hormones. Simply put, there is no known adrenal pool of pregnenolone for one cell to steal away from another, and no known mechanism has been described that could facilitate the transfer of pregnenolone between the mitochondria of different cells (in this case, from the mitochondria of cells within the zona reticularis to those within the zona fasciculata). Unfortunately, the most common figures used to teach steroidogenesis show a common pathway and typically do not specify the differential regulation of available enzymes between different steroidogenic tissues. This leads many to incorrectly assume there is a single “pool” of pregnenolone available for all steroid hormone synthesis within the adrenal. A much better way to teach this is to show the different enzymes available to each cell within the adrenal cortex, showing that each is capable of converting cholesterol to pregnenolone; then to the various needed hormones. This is a figure from the new book- that shows a better way to teach this that avoids showing a single “pool” of pregnenolone for all down-stream hormones.
In addition, the ACTH-driven adrenal synthesis of cortisol is orders of magnitude higher than that of DHEA, and fluctuates radically within a 24-hour period. If there were an adrenal “pregnenolone pool” that contained enough pregnenolone precursors for elevated cortisol production in the morning (or during stress), this “pool” would then also be available for the much smaller amount of needed DHEA production when cortisol synthesis drops even a little. Finally, as decades of steroidogenesis research has shown, the control of adrenal hormone output is regulated mostly by cell-specific enzyme concentrations and external signals coming from outside the adrenal gland (See our latest book for specifics).
What, then, does this mean in relation to cortisol and DHEA output which, when measured, appears to confirm this phenomenon? What about the role of oral pregnenolone therapy for supporting adrenal DHEA production? Well, it’s a bit complicated. While HPA axis stress and subsequent cortisol synthesis and secretion may be related to the acceleration of reduced DHEA production (i.e., a stress-induced down-regulation of DHEA), this relationship is facilitated by regulatory processes (e.g., feedback inhibitions, receptor signaling, genomic regulation of enzymes, etc.), not an intra-adrenal depletion of pregnenolone as a precursor to downstream hormones. For instance, experimentally-induced hyperglycemia and hyperinsulinemia has been shown to affect DHEA and androstenedione production in human subjects., In one study of poorly-controlled type 2 diabetic subjects with elevated cortisol and low DHEA levels, the enzyme necessary for DHEA formation in the zona reticularis (17,20 lyase) was shown to limit the production of DHEA. The enzyme activity was corrected (along with near normalization of cortisol, DHEA and DHEA-S levels) after six months of diet or pharmacotherapy to improve blood glucose control. Additionally, cell-culture studies suggest that under inflammatory stress (IL-4 and other cytokines), the zona reticularis will down-regulate DHEA production when ACTH is present.,These and many other factors (e.g., aging) are likely the driving influences affecting the dynamic relationship between cortisol (activated by the HPA axis) and measured DHEA and/or DHEA-S levels.
By re-assessing the specific mechanisms that drive the stress-related changes in adrenal hormone output, and moving away from older and incorrect explanations, we are able to seek (and perhaps address) the various signals that are actually responsible for modulating adrenal hormone secretion during the progression of chronic stress.
If you are interested in learning more about this subject and how oral pregnenolone and DHEA may improve outcomes in subjects with stress-related dysfunctions, please consider getting our newest book: The Role of Stress and the HPA Axis in Chronic Disease Management.
 Boudou P, Sobngwi E, Ibrahim F et al. Hyperglycaemia acutely decreases circulating dehydroepiandrosterone levels in healthy men. Clin Endocrinol (Oxf). 2006 Jan;64(1):46-52.
 Vásárhelyi B, Bencsik P, Treszl A, et al. The effect of physiologic hyperinsulinemia during an oral glucose tolerance test on the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in healthy young adults born with low and with normal birth weight. Endocr J. 2003 Dec;50(6):689-95.
 Ueshiba H, Shimizu Y, Hiroi N et al. Decreased steroidogenic enzyme 17,20-lyase and increased 17-hydroxylase activities in type 2 diabetes mellitus. Eur J Endocrinol. 2002 Mar;146(3):375-80.
 Woods AM, Judd AM. Interleukin-4 increases cortisol release and decreases adrenal androgen release from bovine adrenal cells. Domest Anim Endocrinol. 2008 May;34(4):372-82
 Woods AM, McIlmoil CJ, Rankin EN. Et al. Leukemia inhibitory factor protein and receptors are expressed in the bovine adrenal cortex and increase cortisol and decrease adrenal androgen release. Domest Anim Endocrinol. 2008 Aug;35(2):217-30
Is it “Adrenal Fatigue”?
Reassessing the Nomenclature of HPA Axis Dysfunction
Sometimes, when we endeavor to understand and describe complicated medical topics, there is a temptation to find a simple explanation to cut through the complexity. These explanations can help bridge the knowledge gap for a while, but as our knowledge grows, they lose some of their original usefulness (e.g., the notion of “good” and “bad” cholesterol). In some cases, those over-simplified explanations actually become a hindrance to helping clinicians and patients understand the important mechanisms and solutions related to chronic conditions. The use of terms like “adrenal fatigue” and “adrenal exhaustion” to summarize the complex dysfunctions related to the stress response is one such explanation. Though these terms have helped dispel the notion that only extreme issues related to adrenal function (Addison’s disease or Cushing’s disease) are of clinical importance, and have become surrogate descriptions for stress-related outcomes, they should now be replaced by more accurate and medically appropriate terms, like HPA axis dysfunction, adrenal insufficiency, or where applicable, hypocortisolism.
While it is true that the most common laboratory method to assess the function of the HPA axis is through the measurement of hormones secreted by the adrenal glands, primarily cortisol and DHEA(S), the mechanisms that control the level of these hormones resides mostly outside of the adrenal gland. Low cortisol and DHEA(S) levels may indeed be related to chronic stress, but as a result of HPA axis adaption (down-regulation) to protect tissues from excess cortisol, have little to do with the inherent capability of the adrenal gland to produce these hormones (see adrenal insufficiency below). While many clinicians (and laboratories) still refer to this as “testing the adrenals,” it is much more accurate to say that such testing is assessing the status of the HPA axis using adrenal hormone measurements as surrogate markers. So, why does this nomenclature reassessment matter?
First of all, using descriptive and accurate terms helps clinicians and patients better understanding the pathophysiology caused by stress and the stress response system. In most cases, issues related to perceived stress, glycemic control, circadian rhythm, cortisol feedback control (in the hypothalamus and/or pituitary), inflammatory signaling, or tissue-specific glucocorticoid effects will have much more to do with a treatment protocol than direct support of adrenal function. For instance, many adaptogenic herbs and nutrients that were once thought to function primarily by supporting adrenal function have been shown to have mechanism that modulate non-adrenal HPA axis or glucocorticoid signaling functions. Related to this is the ability of the clinician to interface appropriately with the vast amount of literature that describes patient outcomes related to stress and HPA axis function. The term “adrenal fatigue” is virtually absent from the peer-reviewed literature and has even caused the Endocrine Society to warn the public against the diagnostic “myth” of adrenal fatigue and to cast suspicion upon clinicians using such terms. While I generally agree with the Endocrine Society that the term “adrenal fatigue” is problematic, I do not agree with them that there is little evidence to connect chronic stress with adverse health outcomes, or that testing adrenal hormone output is of no value beyond diagnosing extreme adrenal disease conditions.
n increasing body of research links a variety of chronic dysfunctions with specific patterns of adrenal hormone output (basal or provoked). By avoiding the use of oversimplified (and incorrect) terminology to describe these relationships and instead choosing more appropriate descriptive terms, the clinician will enhance the credibility of this important phenomenon and be better equipped to incorporate therapies that address the complexity of the whole stress response system.
What are More Appropriate Terms?
HPA Axis Dysfunction (or Maladaption): This term is much more appropriate to describe the many consequences that link stress (allostasis) with the myriad of measurable negative outcomes related to the stress response. The majority of these outcomes can be linked in some manner to processes controlled by the HPA axis. Alternatively, some refer to these as “disorders of the stress system” or the “consequences of the maladaption to stress.”
Hypocortisolism: This is the most descriptive term to use when measured cortisol is well below the laboratory reference range. Still, it is a relative term and does not necessarily implicate dysfunction or “fatigue” of the adrenal gland. Extreme hypocortisolism is associated with Addison’s disease and other forms of primary and secondary adrenal insufficiency. Reduced HPA axis function resulting in low cortisol levels is common in PTSD, fibromyalgia, chronic fatigue syndrome, certain affective disorders, and individuals with high psychosocial “burnout”. Other specific terms for different stress-related HPA axis phenomena include hypercortisolism, loss of HPA circadian function, and low circulating DHEA(S).
Adrenal Insufficiency: This is a clinical manifestation that results in a deficient production or action of glucocorticoids, a condition that has potential life-threatening consequences. Primary adrenal insufficiency (i.e., Addison’s disease) describes diseases intrinsic to the adrenal cortex primarily caused by autoimmune adrenalitis. Secondary adrenal insufficiency relates to insufficient pituitary ACTH or intrinsic defects in the adrenal responsiveness to ACTH. Tertiary adrenal insufficiency results from impaired synthesis of hypothalamic CRH or AVP. The most common cause of tertiary adrenal insufficiency is the chronic use of exogenous glucocorticoids (pharmacotherapy), leading to the suppression of hypothalamic secretions of CRH. True adrenal insufficiency will almost always require hydrocortisone replacement therapy (often life-long). For a complete review of the etiology, pathophysiology, clinical presentation, diagnosis and treatment approaches to adrenal insufficiency, see Charmandari, et al.[i]
[i] Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014 Jun 21;383(9935):2152-67.