By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix
Why Use L-Theanine in Your Practice?
Many practitioners have their ‘favourite’ nutrient or herbal treatment for patients who present with high stress levels, anxiety or difficulty falling asleep. Indeed, there are many great options that can positively address all three of these interconnected concerns. A few favourites include GABA, 5-HTP, inositol, lavender, and, of course, magnesium. Yet, in select cases, the amino acid L-theanine deserve to be considered.
For practitioners that are less familiar with the nutrient, L-theanine is a single amino acid, naturally found in green tea, that is well-known to calm the mind and improve focus. Research has found that L-theanine can increase levels of various neurotransmitters in the brain, such as serotonin, dopamine and GABA[i], while also blocking excitatory glutamate receptors.[ii] Ultimately, the actions of L-theanine lead to an increase in alpha-brain waves and create a calm, yet focused, state. [iii] Clinical trials have confirmed that, in individuals given supplemental L-theanine, these effects can reduce anxiety and improve stress markers such as heart rate, blood pressure and salivary immunoglobulin A.[iv] [v] [vi]
This information is important, from a clinical perspective, for a number of reasons. First of all, positively impacting multiple neurotransmitters, as opposed to targeting just one in particular (i.e.GABA or serotonin), has inherent advantages. Unless laboratory confirmation or other clear signs of a specific single neurotransmitter imbalance are present, a balanced approach is justified and sound. Arguably, this is also a gentler approach with a reduced likelihood of negative side-effects.
Secondly, although L-theanine can calm an overactive mind, it does so without jeopardizing alertness or causing sedation. In fact, the increase in alpha-brain wave activity helps to increase focus. Clinically, this means that L-theanine is a great option for stressed-out students that are studying for exams but still need to be cognitively sharp! Similarly, many practitioners will use L-theanine in children with attention deficit-hyperactivity disorder (ADHD) or for adults working in highly stressful and demanding environments.[vii]
Finally, L-theanine is a useful and practical clinical option for a broad range of patient profiles. L-theanine is an extremely safe option for daily use[viii]. Various research also shows that it positively affects alpha brain waves within just 30 minutes after ingestion.[ix] This means that L-theanine can be used acutely, preventatively, or on an ongoing basis to improve mood, cognition, sleep and stress-coping. Capsules can also be opened and mixed in water throughout the day or the powder can be dissolved under the tongue for quick-action. The evidence-based dosage ranges from 50-400mg per day and is highly variable depending on the clinical indications and individual circumstances.
[i] J Herb Pharmacother. 2006;6(2):21-30.
[ii] Biosci Biotechnol Biochem. 2002 Dec;66(12):2683-6.
[iii] Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8.
[iv] Hum Psychopharmacol. 2004 Oct;19(7):457-65.
[v] Biol Psychol. 2007 Jan;74(1):39-45.
[vi] J Physiol Anthropol. 2012 Oct 29;31:28.
[vii] Altern Med Rev. 2011 Dec;16(4):348-54
[viii] Food Chem Toxicol. 2006 Jul;44(7):1158-66
[ix] Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8.
By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix
For years now, we have heard about the seemingly endless benefits of vitamin D3. Indeed, vitamin D3 deserves a lot of this attention because of its role in up-regulating calcium absorption, proper immune function, mood health, cardiovascular function, skin health, gene expression and more. But now that the message is out about vitamin D3, it’s time to shift our focus to an equally deserving nutrient for optimal health: Vitamin K2.
Simply put, vitamin K2’s job is to ensure that calcium is directed to the bones and away from the cardiovascular system. Vitamin K2 achieves this shunting of calcium through the carboxylation and activation of various proteins, including osteocalcin and matrix-GLA protein. Osteocalcin is responsible for regulating bone mineralization while Matrix-GLA protein binds up free floating calcium and prevents its deposition into arteries. Getting more calcium into the bone has obvious implications for osteoporosis, but let’s consider the profound impact on cardiovascular disease.
Various studies have demonstrated the importance of vitamin K2 and carboxylation for heart health. A population-based study of 4,807 people with no past medical history of myocardial infarctions showed a strong inverse relationship between vitamin K2 intake and severe arterial calcification, coronary heart disease (CHD), CHD mortality and all-cause mortality.[i] In a follow-up to this trial, the PREVEND study followed 4,275 participants for 10 years and found a significant association between uncarboxylated Matrix GLA protein (the best marker for suboptimal vitamin K2 status), all-cause mortality and cardiovascular mortality.[ii] Elderly individuals with the highest uncarboxylated Matrix GLA protein levels have been found to have more than double the risk of CVD! [iii]
With these strong correlations and a better understanding of carboxylation levels, it only made sense to investigate vitamin K2 as an intervention for heart health, and the results have not disappointed. For example, a double-blind, placebo randomized control trial (RCT) of 244 healthy postmenopausal women examined arterial stiffness index to determine whether vitamin K2 had a positive impact on cardiovascular function.[iv] After 3 years of supplementing with 180ug of vitamin K2 per day, the arterial stiffness index was significantly improved and there was a corresponding 50% decrease in uncarboxylated Matrix GLA protein levels in the blood compared to the placebo group.
What about vitamin K2 in special populations? A double-blind RCT of 42 people with non-dialyzed chronic kidney disease found that 90ug vitamin K2 and 10ug vitamin D3 improved carboxylation numbers and reduced progression of atherosclerosis much better than just 10ug of vitamin D3 per day.[v] Even athletes can gain from the cardiovascular benefits of vitamin K2. A double-blind RCT of 26 trained male and female athletes found a 12% significant increase in maximal cardiac output after receiving 300 ug/day for 4 weeks and then 150 ug/day for an additional 4 weeks.[vi] This is a powerful change in a highly-trained and healthy population.
Given the ever-rising incidence of cardiovascular disease and associated impact on quality of life and mortality, it is becoming almost negligent to not prescribe vitamin K2 for all of our patients. The research is quite convincing. With the common practice of vitamin D3 supplementation and the subsequent increased absorption of calcium into the bloodstream, the need for vitamin K2 has never been greater. In almost all clinical circumstances where vitamin D3 is indicated, I recommend the addition of vitamin K2 so that patients receive the benefits of greater calcium absorption and bone support without increasing their risk of heart disease.
K2-D3 Matrix by Cyto-Matrix features 120mcg of menaquinone-7 (MK-7) per softgel, the preferred form of vitamin K2 because of its exceptional 72-hour half-life in the bloodstream and improved delivery to blood vessels and bones. This particular MK-7 is found as K2Vital®, soy-free and micro-encapsulated with a starch bilayer for superior protection against harsh environments and increased stability in the presence of minerals. K2-D3 Matrix also contains 1000IU of Vitamin D3 and a medium chain triglyceride oil base sourced from organic coconut oil to encourage optimal bioavailability. K2-D3 Matrix is additionally offered in a liquid dropper bottle for patient preference.
[i] J Nutr. 2004 Nov;134(11):3100-5.
[ii] Nutrients. 2017 Dec 8;9(12). pii: E1334.
[iii] Maturitas. 2014 Feb;77(2):137-41.
[iv] Thromb Haemost. 2015 May;113(5):1135-44.
[v] Pol Arch Med Wewn. 2015;125(9):631-40.
[vi] Altern Ther Health Med. 2017 Jul;23(4):26-32
By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix
The holidays are just around the corner and festive gatherings are in full swing: work parties, social outings and a sharp rise in baked goods all come together to make our personal health goals and the goals of our patients that much more difficult!
An online search for ways to curb these cravings will yield a lot of generic and common sense suggestions: more sleep, more water, more healthy foods and more planning ahead. These can help. However, targeted clinical interventions can sometimes help our patients achieve more concrete results.
Here are the top 5 interventions for reducing food and sugar cravings for your consideration:
- Inositol Powder: Inositol’s role in the body is to modulate receptor sensitivity. It can aid in mood health by regulating the activity of neurotransmitter receptors, just as it can improve PCOS outcomes by regulating insulin receptors. It turns out that both of these actions may explain Inositol’s benefits for cravings and addictions. A small double-blind crossover study examined inositol as a therapeutic tool in those with binge eating behaviours and found that 18 grams per day for 6 weeks led to significant improvements in eating patterns.[i] Anecdotally, I have used inositol powder in a number of patient cases with addictions ranging from sugar to cocaine. Although inositol is not typically the sole therapeutic intervention, I have seen success in controlling the addictive behaviours at doses of even 6-9 grams per day.
- Chromium: Although this mineral is well-known for its ability to regulate insulin receptor sensitivity and blood sugars in diabetics, its use for controlling cravings in seemingly normoglycemic individuals is overlooked. One study in people with major depressive disorder or dysthymia examined the use of 400-600 mcg of chromium picolinate per day for 8 weeks and found significant reductions in depressive symptoms and carbohydrate cravings, when compared to placebo.[ii] This makes sense, given that a better regulated mood and blood sugar level should, in turn, lead to fewer cravings.
- L-Glutamine: There are many anecdotal reports by practitioners of L-Glutamine’s ability to curb sugar cravings and I have seen this work in my own practice with select patients. The theory is that glutamine may improve insulin sensitivity and some portion of it may be directly converting to glucose in the body, thereby negating the crave.[iii] Higher protein intake in general does improve cravings and satiety throughout the day[iv] [v], but may not entirely explain the quick-acting effects. The point is: it works well acutely for cravings. I have seen 2.5-5 grams work well.
- Consider Mood Disorders: Food cravings are by no means a diagnostic feature of depression or anxiety, but if you or your patient suffer from either, there’s a much higher likelihood for sugar cravings.[vi] Some of it is physiological – we need carbohydrates to upregulate the production and release of serotonin in the brain.[vii] In many cases, it may be physiological and psychological, with food binging acting as the coping mechanism. Regardless, if you want to nip those cravings in the bud, addressing the underlying mental health component is a must.
- Gymnema sylvestre: This is an ancient herb that has traditionally been used for the management of blood sugars. Indeed, research today has confirmed that it can help to regulate blood sugar levels and HbA1c.[viii] However, gymnema is unique in that, when its leaves are chewed or come in direct contact with taste bud receptors, it interferes with the ability for the brain to sense “sweet” tastes. This makes them a useful tool for curbing sugar cravings in those interested in teas or chewable options. Internally, gymnemic acids blunt sugar uptake into the bloodstream and inhibit the peripheral utilization of glucose, so there is also an ongoing benefit for sugar regulation and food cravings. [ix]
To summarize: Address hormonal imbalances. Basic lifestyle improvements such as regular sleep and targeted nutrients such as inositol both generate the majority of their benefits from the regulation of insulin, blood sugars, neurotransmitters, cortisol and stress.
Even though stress wasn’t explicitly discussed above, it is well recognized that stressors can influence eating patterns[x], and that stressed individuals experience more cravings and consume more calories[xi]. Perhaps I take it for granted that every ND and integrative healthcare practitioner is addressing stress and hormonal imbalances in all cases! “Treat the root cause”. What else is new?
[i] Gelber D, Levine J and Belmaker RH. Effect of inositol on bulimia nervosa and binge eating. Int J Eat Disord. 2001 Apr;29(3):345-8.
[ii] Docherty JP, Sack DA, Roffman M, Finch M, Komorowski JR. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract. 2005 Sep;11(5):302-14.
[iii] Mofino et al. Metabolic effects of glutamine on insulin sensitivity. Nutritional Therapy & Metabolism 2010; 28 (1): 7-11
[iv] Leidy HJ, Tang M, Armstrong CL, Martin CB, Campbell WW. The effects of consuming frequent, higher protein meals on appetite and satiety during weight loss in overweight/obese men. Obesity (Silver Spring). 2011 Apr;19(4):818-24.
[v] Hoertel HA, Will MJ, Leidy HJ. A randomized crossover, pilot study examining the effects of a normal protein vs. high protein breakfast on food cravings and reward signals in overweight/obese “breakfast skipping”, late-adolescent girls. Nutr J. 2014 Aug 6;13:80.
[vi] Wurtman, R.J. and Wurtman, J.J. 1995. Brain serotonin, carbohydrate-craving, obesity and depression. Obesity Res 3(4): 477S–480S.
[vii] Wurtman J, Wurtman R. The Trajectory from Mood to Obesity. Curr Obes Rep. 2017;7(1):1-5.
[viii] Baskaran K, Ahamath BK, Shanmugasundaram KR and Shanmugasundaram ER. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990;30:295-305.
[ix] Kanetkar P, Singhal R, Kamat M. Gymnema sylvestre: A Memoir. J Clin Biochem Nutr. 2007;41(2):77-81.
[x] Yau YH and Potenza MN. Stress and eating behaviors. Minerva Endocrinol. 2013 Sep;38(3):255-67.
[xi] Epel E, Lapidus R, McEwen B and Brownell K . Stress may add bite to appetite in women: a laboratory study of stress-induced cortisol and eating behavior. Psychoneuroendocrinology. 2001 Jan;26(1):37-49.
Did you know that melatonin can help improve various aspects of your sleep? Well, of course you did. Anyone with a basic understanding of human physiology and the natural health industry knows that melatonin and sleep go hand-in-hand. But I would argue that very few people realize the wide-reaching effects of melatonin to impact, say, digestion, skin health and inflammation.
Yes, melatonin is the body’s hormone designed to regulate our circadian rhythm and supplementation has been shown to improve total sleep time and restfulness, speed recovery from jet lag, and improve transition periods for shift workers.[i] [ii] [iii] But melatonin actually has some solid research in many areas outside of sleep.
Here are some other indications for melatonin supplementation in your patients:
Heartburn: Research has found that melatonin protects the esophageal lining by increasing mucous production. A melatonin dose of 3mg/day for a period of 4-8 weeks can actually improve heartburn symptoms.[iv] Another study showed that 6mg/day, in combination with various other nutrients such as B-vitamins and l-tryptophan, also improved heartburn symptoms significantly.[v]
Gastritis: Melatonin has been shown to improve symptoms in people with stomach pains not caused by ulcerations in the tissue. 5mg/day over a period of 12 weeks significantly improved pain markers.[vi] A more recent study in children with the same concern found no benefit but this trial lasted for only 2 weeks.[vii]
Irritable Bowel Syndrome: A number of small studies have found that 3mg/day of melatonin may improve symptoms of IBS such as pain, abdominal distension and urgency, regardless of its impact on sleep measures.[viii]
Eczema: In children and teenagers with eczema, melatonin was able to reduce itchiness and discomfort by 20% while reducing the time it took to fall asleep by over 20 minutes due to this reduction in irritation.[ix]
Migraines: Over a 3-month trial, melatonin was found to be more effective than placebo for reducing headache frequency in migraine sufferers. Headaches reduced from an average of 7.3 per month at baseline to an average of 4.6 headaches per month after melatonin treatment.[x] Additionally, the benefits of melatonin were found to be just as effective as the drug amitriptyline with far fewer side effects.
Tinnitus: Melatonin has been found to decrease the perception of ringing in the ears by up to 40% on its own. This is comparable to the efficacy of the drug sulpiride for tinnitus and, even better, it appears that the combination of the 2 treatments may be the most effective option (up to an 81% reduction).[xi]
Cancer care: Although cancer care is complex and absolutely must be handled by an experienced and qualified practitioner, it is worth noting that there is a plethora of research for this field of application. Melatonin shows promise for many solid tumors at dosages of 10-20mg/day, although there are even studies as high as 40mg/day. Often melatonin is used in conjunction with pharmaceuticals (such as tamoxifen) or with chemotherapeutics to reduce the side effects and/or increase tolerability.[xii]
Endometriosis: One study examined melatonin use in 40 females with endometriosis, finding that 10mg/day significantly reduced pain by 40% (including pain with intercourse and during menstruation) and the need for pain medications by 80%. [xiii]
In clinical practice, this makes melatonin a great “2-for” treatment, meaning that you attack 2 birds with 1 stone or 2 symptoms with 1 intervention: if you see a patient with sleep concerns and IBS, consider melatonin. Another patient presents with tinnitus and he or she is a shift worker with sleep issues? Think melatonin.
Many people may find benefits with even 0.5 mg or 1mg per day for sleep, and higher doses can cause grogginess in those that are sensitive. Others may need 5 to 10mg to find benefit. For this reason, starting low and going slow when it comes to titration of melatonin dosage is certainly recommended.
[i] Xie Z, Chen F, Li WA et al. A review of sleep disorders and melatonin. Neurol Res. 2017 Jun;39(6):559-565.
[ii] Herxheimer A and Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;(2):CD001520.
[iii] Sadeghniiat-Haghighi K, Aminian O, Pouryaghoub G et al. Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial. Journal of Circadian Rhythms. 2008;6:10.
[iv] Kandil TS, Mousa AA, El-Gendy AA et al. The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterol. 2010 Jan 18;10:7.
[v] Pereira Rde S. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and amino acids: comparison with omeprazole. J Pineal Res. 2006 Oct;41(3):195-200.
[vi] Klupińska G, Poplawski T, Drzewoski J et al. Therapeutic effect of melatonin in patients with functional dyspepsia. J Clin Gastroenterol. 2007 Mar;41(3):270-4.
[vii] Zybach K, Friesen CA, Schurman JV et al. Therapeutic effect of melatonin on pediatric functional dyspepsia: A pilot study. World J Gastrointest Pharmacol Ther. 2016 Feb 6;7(1):156-61.
[viii] Saha L, Malhotra S, Rana S et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol. 2007 Jan;41(1):29-32.
[ix] Chang YS, Lin MH, Lee JH et al. Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance: A Randomized Clinical Trial. JAMA Pediatr. 2016 Jan;170(1):35-42
[x] Gonçalves AL, Martini Ferreira A, Ribeiro RT et al. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1127-32.
[xi] Lopez-Gonzalez MA, Santiago AM, Esteban-Ortega F et al. Sulpiride and melatonin decrease tinnitus perception modulating the auditolimbic dopaminergic pathway. J Otolaryngol. 2007 Aug;36(4):213-9.
[xii] Mills E, Wu P, Seely D, et al. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005;39:360-366
[xiii] Schwertner A, Conceição Dos Santos CC, Costa GD et al. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013 Jun;154(6):874-81.
By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix
Depression and anxiety are conditions that affect us all, either personally or through the suffering of friends, family and patients. While there are a seemingly endless number of factors to consider that are unique to each individual, one area that should always be addressed is nutritional status.
Anecdotal evidence and clinical research has shown us that mental health concerns can arise in the presence of single or multiple nutrient deficiencies. Here is a brief summary of some of the most common nutrients to consider when treating mental health:
Magnesium: Although we typically associate magnesium with musculoskeletal function, it has been shown to increase brain-derived neurotrophic factor (BDNF) and GABA, while down-regulating ACTH and blocking NMDA receptors. Benefits for improving depression markers have been seen with supplementation after only 1-2 weeks in many different forms (such as oxide, glycinate and taurinate). Although clinical trials have shown benefits for depression and anxiety between 125-300mg of elemental magnesium per day, clinically it may be most useful to dose to bowel tolerance.
Zinc: The hippocampus, the area of the brain responsible for emotion, memory and motivation, has one of highest concentrations of zinc in the body. Many studies have shown that lower zinc levels are associated with depression, and interventional trials support its use for this purpose. Specifically, zinc sulphate has successfully been used in Multiple Sclerosis patients and zinc gluconate has been used in obese patients, with both improving Beck Depression scores after 12 weeks. The evidence based dose is 25-50mg of elemental zinc per day and zinc supplementation can also safely improve SSRI outcomes.
B-vitamins: A 2015 Systematic Review found that B12 and Folate reduced the onset and relapse risk for depression with long-term supplementation. Similarly, a combination of 500mcg vitamin B12, 2mg Folate and 25mg vitamin B6 has been shown to improve antidepressant medication response over a full year. Clinically, a well-balanced B-complex supplement or intramuscular methylcobalamin and folate injections can have an immediate positive impact on mood and energy, if patients have suboptimal levels. I prefer my mental health patient’s serum B12 levels to be above 500 pmol/L.
Iron: Iron is not only needed for hemoglobin synthesis, but also serotonin production and the proper conversion of thyroxine (T4) to triiodothyronine (T3). Although no interventional studies have been done with iron and depression or anxiety, there is a strong and convincing correlation noted between low hemoglobin and depression with a dose-response relationship, meaning those with worse anemia demonstrate more severe depression. Ferritin levels below 45 ng/mL and hemoglobin below 120 g/L for women (less than 130 g/L for men) are associated with depressive symptoms
Vitamin D: Higher serum levels have been associated with a 43% lower risk of depression and panic disorder, with various interventional trials showing benefits for depression with a wide range of dosing (ie 50,000 IU/week vs. 2,000 IU/day). Similarly, benefits for vitamin D supplementation in depressed adolescent females, obese populations and perinatal mothers has been demonstrated. However, there are also many interventional trials showing lack of benefit which could be due to adequate vitamin D status in subjects at baseline. The target blood levels for optimal mood should be 75 nmol/L or greater.
Omega-3’s: A 2018 analysis of 19 RCTs found that fish oil supplementation provided a modest improvement in those with anxiety, with a greater effect in those taking more than 2,000mg/day of combined EPA and DHA. When it comes to depression, some evidence has shown that it is not beneficial to simply restore polyunsaturated fatty acid (PUFA) status in the body, but rather that omega-3’s can be beneficial in cases of systemic inflammation. In fact, your depressed patients are most likely to respond to omega-3 supplementation if their high sensitivity C-reactive protein (hs-CRP) is above 3.0. The evidence based dosage in depression is 1000-2000mg of EPA per day.
Selenium: Time to eat those brazil nuts! There are at least 5 studies associating low selenium with depression & anxiety, while one interventional study of 100mcg/day improved mood after only 5 weeks.
When it comes to choosing the right nutrient(s) for supplementation, lab testing, clinical signs and symptoms, and knowledge of common medication depletions should be considered. But the take home message from all of this should be that, when it comes to mental health, diet matters…a lot. There are many nutrients necessary to keep the brain balanced.
Perhaps the best study to illustrate this was the 2017 RCT of 67 individuals with moderate to severe depression. After 12-weeks of eating a modified Mediterranean diet, 32% went into remission compared to only 8% of the control group. The key here is that the dietary intervention was ad libitum, meaning the focus was on food quality and not calories. The group was even allowed up to 3 servings per week of “extras” such as refined sugars, alcoholic drinks and fast-foods, showing that it doesn’t need to be an “all-or-none” approach.
Even encouraging patients to “Eat the rainbow” to get a wide variety of nutrients and to focus on “Eating whole foods” to reduce sugars and additives is often an easy starting point for many individuals that feel overwhelmed with dietary changes. In fact, simply reducing the glycemic index of foods can reduce the risk for depression.
When it comes to mental health, part of the solution for our patients may be simpler than we think. In the words of Michael Pollan, “Eat real food. Not too much. Mostly plants.”
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randomized, double-blind, placebo-controlled trial. Nutrition, Volume 35, 56 – 60.
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 Levenson CW. Zinc: the new antidepressant? Nutr Rev. 2006 Jan;64(1):39-42.
 Salari S et al. Zinc sulphate: A reasonable choice for depression management in patients with multiple sclerosis: A randomized, double-blind,
placebo-controlled clinical trial. Pharmacol Rep. 2015 Jun;67(3):606-9.
 Solati Z et al. Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in
overweight or obese subjects: a double-blind, randomized, placebo-controlled trial. Nutr Neurosci. 2015 May;18(4):162-8.
 Nowak G, Szewczyk B, Pilc A. Zinc and depression. An update. Pharmacol Rep. 2005 Nov-Dec;57(6):713-8.
Almeida OP, Ford AH and Flicker L. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin
B12 for depression. Int Psychogeriatr. 2015 May;27(5):727-37.
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middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial. Br J Psychiatry. 2014 Sep 25.
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population. Psychosom Med. 2012 Feb-Mar;74(2):208-13.
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findings. Clin Nutr. 2013 Jan 21.
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Week Follow-Up Study. J Diet Suppl. 2017 Jul 31:1-10.
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Pregnancy Childbirth. 2016 Aug 20;16:239.
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trial. J Intern Med. 2008 Dec;264(6):599-609.
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Systematic Review and Meta-analysis. JAMA Network Open.2018;1(5):e182327. doi:10.1001/jamanetworkopen.2018.2327.
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long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population. Prostaglandins Leukot Essent Fatty Acids. 2008
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By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix
Up to 50% of male infertility cases have no clear cause and sperm counts continue to dwindle. Yet, countless research studies have uncovered environment factors that may contribute to male infertility through their negative impact on sperm parameters. This means that there are also countless treatment avenues to explore with our male fertility patients.
If physical and anatomical obstructions are ruled out as causes of infertility, consider this step-wise approach for male patients either struggling with fertility due to poor sperm health (i.e. documented low sperm counts and/or poor motility and morphology) or looking to optimize their fertility through proactive means:
Step 1: Address diet
It’s no surprise that diet must be the foundational treatment for improving male fertility. Although many of these changes may seem common sense, they are important to reinforce with your patients before exploring more targeted treatments:
- Remove or reduce alcohol, marijuana, caffeine and cigarette smoke: Collectively, an increased exposure to these substances has shown a dose-dependent increase in free radical production, reduction in semen amounts, and worse sperm motility and morphology.  
- Add healthy fats: Research has shown that just 75 grams per day of walnuts, a whole food source of polyunsaturated fatty acids, added to a typical Western diet can improve sperm counts, morphology and motility. This study confirms other research showing that there are lower levels of Omega-3 fatty acids in infertile men when compared to fertile males, and that EPA and DHA supplementation can improve sperm counts and concentrations. Finally, excess saturated fat intake is associated with reduced semen volume.
- Remove refined sugars: As if we needed another reason to advise patients to avoid refined sugars, research has shown that even just an increased consumption of sugar-sweetened beverages (greater than 1.3 per day) can significantly reduce sperm motility.
- Consider organic: Reduced pesticide exposure through organic food choices may make a powerful impact on the sperm quality of your male population. A 2008 review found that increased pesticide exposure can affect spermatogenesis and may prolong time-to-pregnancy.
It should be noted that both obesity and being underweight have been associated with lowered testosterone and poor sperm count, respectively. When appropriate, a focus on healthy weight management should be encouraged.
Step 2: Review personal care products
Education surrounding environmental toxin exposure is key when discussing male fertility concerns.
In addition to other ‘clean-living’ options such as choosing Bisphenol A (BPA)-free options in plastics and cans, consider the impact of these important endocrine disruptors:
- Triclosan: This anti-microbial agent commonly found in toothpaste, deodorants, shampoos and other household products, has been demonstrated to be negatively associated with normal sperm morphology, concentration and count.
- Parabens: Commonly discussed in the context of xenoestrogen activity and female fertility concerns, these preservatives appear to damage mitochondrial function in sperm.  A 2017 study showed that urinary paraben levels were significantly associated with abnormal morphology, decreased sperm motility and decreased testosterone levels.
- Phthalates: The compounds commonly found in plastics and, unfortunately, also beauty products, have also been shown to negatively impact sperm parameters. For example, one study found urinary mono-methyl-phthalate (MMP) concentrations to strongly correlate with sperm concentration, length and maturity.
Step 3: Add in antioxidant support
Now that you have done some removal, it’s time to add more of the good stuff! Antioxidants help to quench the reactive oxygen species that are generated often in response to environmental exposures and, ultimately, reduce the damage done to sperm mitochondria.
A number of reviews and meta-analyses have definitively demonstrated the ability for antioxidants to not only improve sperm parameters, but also increase live birth rates and pregnancy rates in subfertile couples.
Consider a combination of the following antioxidants:
- Vitamin C: A dose-dependent improvement in sperm motility has been found with vitamin C supplementation in smokers.  Many studies have used ascorbic acid in combination with vitamin E and zinc for improved sperm parameters.
- Vitamin E: Tocopherols are a well-known group of antioxidants that are widely deficient in the modern-day diet. Vitamin E has been shown to improve sperm parameters on its own, but particular improvements have been noted when it is combined with selenium, and vitamin C.
- Selenium: Not only is selenium beneficial for sperm parameters when combined with Vitamin E or N-acetylcysteine, but solo supplementation also shows benefit for sperm counts and motility (100 mcg over 3 months). This makes sense given that selenium is necessary for proper spermatogenesis.
- Zinc: Zinc’s function in various aspects of male health, including testosterone production, has long been studied and its impact on fertility and spermatogenesis is no different. A recent meta-analysis of 20 studies found that zinc concentrations in seminal plasma were significantly lower in infertile males and that supplementation is capable of increasing semen volume, while also improving sperm motility and morphology. Zinc in combination with folate has also shown benefit for sperm count
- L-Carnitine and Acetyl-L-Carnitine: Carnitine provides energy to the sperm by transporting fatty acids into the mitochondria, thereby improving sperm motility. Over a dozen human clinical trials have confirmed the use of either L-carnitine, Acetyl-L-carnitine (the form capable of entering the central nervous system) or a combination of both for improved sperm motility, while a number of these same studies have shown improved pregnancy rates.
- N-acetylcysteine: most well-known for its ability to increase glutathione levels, at only 600mg/day this amino acid can improve sperm motility and volume. The addition of 200mcg/day of selenium has found even better results in these areas, also with improved sperm morphology.
There are many other antioxidants that have shown benefits for improving sperm markers. The key is to individualize your treatments to target patient-specific dietary and environmental factors. Also consider coenzyme-Q10, arginine, astaxanthin, lycopene, folate and melatonin.
Step 4: Address stress and consider botanicals and acupuncture
Although diet, lifestyle and nutritional support have a profound ability to improve male fertility outcomes, stress management needs to be considered as elevated stress can alter testosterone levels and, thereby, sperm numbers and functionality.
Many stress reduction techniques may be indicated (i.e. deep breathing) but herbal extracts can act through multiple mechanisms. For example, adaptogens with the ability to positively impact the HPA-axis can also provide powerful antioxidant support.
Two herbs to consider include:
- Mucuna pruriens: Also known as velvet bean, this herb contains a high concentration of dopamine, can improve psychological stress scores and also improve sperm parameters.
- Withania somnifera: More commonly known as ashwagandha, this adaptogenic herb is best known for its ability to reduce stress and anxiety, but it is also a traditional aphrodisiac capable of treating male sexual dysfunction and infertility. A 2013 placebo-controlled study confirmed this ancient wisdom by showing significant improvements in sperm parameters after 3 months of treatment intervention with 225mg, three times per day. A 167% increase in sperm count was seen, with a 53% increase in sperm volume, a 57% increase in sperm motility and a 17% increase in testosterone levels.
Other herbs to consider with positive research for male fertility outcomes include Eurycoma longifolia, Mucuna pruriens and Panax Ginseng.
Finally, acupuncture may be an appropriate intervention capable of not only reducing stress, but also improving blood flow to the testicles and, thereby, offering multiple mechanisms for improved fertility outcomes.
Various studies have shown acupuncture may be beneficial for male infertility through scrotal temperature control, increased testosterone and improved sperm parameters. 
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By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix
Every healthcare practitioner should be able to rhyme off the keynote symptoms of iron-deficiency: fatigue, weakness, dizziness and pallor (pale skin) probably come to mind first. This makes sense given that iron is the most commonly deficient nutrient in the world and a concern often seen in private practice. But the implications of suboptimal iron extend much further than low hemoglobin and low energy. Iron is needed for so much more.
Many practitioners, myself included, have likely missed opportunities to successfully treat patients with iron restoration therapies over the years because of more “atypical” signs and symptoms of inadequate iron. Yes, iron is classically needed in hemoglobin formation and, therefore, oxygen delivery and energy levels, but here are some other conditions and physiological functions that may warrant a more thorough exploration of iron levels:
Restless Leg Syndrome (RLS): Iron deficiency has been found to be a common cause of RLS occurring in about 25% of cases! Supplemental iron is certainly most effective in those with documented iron deficiency, however, some patients respond to iron supplementation even without anemia. Iron is thought to be beneficial for RLS through its ability to upregulate dopamine synthesis (it is needed to convert tyrosine into dopamine). If the RLS is refractory to iron therapy, consider deficiencies of magnesium, B12 and vitamin E instead.
Female Infertility: Case reports have found that iron supplementation resulted in pregnancy within 28 weeks in infertile woman with borderline low ferritin levels (14-40 ng/mL). Certainly, this is not to say that iron is the ‘silver bullet’ for female infertility, but it deserves attention amidst all other factors.
Diffuse Hair Loss: General hair loss can be a symptom of iron deficiency, even before anemia sets in. Restoring optimal iron levels has been shown to offset this symptom and iron supplementation can also be useful in cases of brittle, dry and splitting hairs (if you’re having compliance issues with iron supplements in iron-deficient female patients, this may be worth mentioning!)
Poor Immune function: Iron is needed for proper immune function through cytokine production in macrophages and an iron-deficient state may lead to an insufficient immune response. For example, one study in individuals with oral candidiasis found that iron restoration led to lower salivary candida counts and reduced oral lesions.
Thyroid Function: We classically discuss the need for selenium to convert T4 into the more bioactive T3, but iron is another mineral that is necessary to promote this conversion through deiodinase activity (and iron is also needed for thyroid peroxidase action). To make matters worse, low thyroid function can lead to worse iron absorption. In cases of hypothyroidism with concomitant iron deficiency, combination treatment with iron and levothyroxine has been shown to be superior over each therapy alone.
Menorrhagia (heavy menstrual bleeding): Substantial blood loss can obviously lead to iron deficiency. However, few people are aware that an iron deficiency can actually cause a recurring state of heavy menstrual bleeding through weakened uterine muscles that cannot properly clamp down on blood vessels (iron is a cofactor for cytochrome oxidase, an enzyme necessary for muscle contraction). Ultimately, interventional trials confirm that iron supplementation is necessary not only for symptom control but also to reduce the heavy bleeding itself.
Cognition, Mood & Intelligence: It is well-documented that children and adults perform poorer on mental function tests in states of iron deficiency, with areas such as attention, memory and concentration being affected. This is the case even in the absence of outright anemia. Mechanistically, inadequate iron supply leads to a dysregulation of dopamine and serotonin metabolism. Both animal trials and human studies have shown that severe iron deficiency during infancy may have long-standing implications on brain health that persist well into adulthood, regardless of adequate iron intake later on in life.
As clinicians, it is easy to start down a rabbit-hole to find a medical explanation for complex issues. Yet, it’s generally best to follow the principle of ‘Occam’s razor’: the simplest solution is typically the correct solution. If a patient is vegan, has heavy bleeding or any of the conditions listed above, get back to the basics and test their hemoglobin, ferritin and other blood markers. A well-absorbed iron might be the simple answer that you and your patients are looking for.
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By: Dr. Colin O’Brien ND, Ontario Regional Manager, Cyto-Matrix
Summer has once again come and gone and it’s time to get back into a solid routine. Whether you’re a parent with toddlers headed back to school, a graduate student or just an everyday worker going back into the office after some vacation time, we all could use a little extra support to help us push through the busy fall season. Regular sleep, a healthy diet and moderate exercise will always be the foundation for stress resiliency, but when more support is needed, a little-known herb called Rhodiola rosea can help your body adapt and adjust accordingly.
What is Rhodiola?
Rhodiola rosea, also known as ‘golden root’, is a medicinal herb that has traditionally been used in Russia, Scandinavia and other European countries for a wide variety of health concerns. It is considered an adaptogenic herb, meaning that it can help your body adapt to stress! As you can imagine, the ability to increase resiliency to stress is highly sought after by many parents, students, workers and others in high pace lifestyles, so the popularity of rhodiola has been growing steadily in North America.
Why Should You Consider Using Rhodiola?
Traditionally, rhodiola has been used as a stimulant, to increase attention span, memory and physical endurance, but also to treat a wide variety of health concerns such as anxiety, depression, fatigue, anemia, infections and impotence. Most importantly, rhodiola is particularly effective for these concerns when stress is at the root cause of the problem.
Clinical research has been able to confirm many of these wonderful applications for rhodiola root extract. Here are a few highlights:
Burnout: Although rhodiola has been traditionally used for this purpose for many years, brand new research has supported its ability to help people suffering from symptoms of burnout. 118 men and women between the ages of 30-60 took rhodiola rosea extract for 12 weeks and significant improvements were noted in areas of emotional exhaustion, fatigue and joy. An increased ‘zest of life’ and sexual interest and functioning were also found in those taking rhodiola root.
Exercise Performance & Recovery: Research has shown that even short term dosing (ie 4 days) of rhodiola can increase time to exhaustion and oxygen utilization during athletic performance. Perhaps just as important, rhodiola has been found to reduce levels of inflammation in the body 5 hours post-exercise and also 5 days after intense exercise, meaning that it can speed recovery times.
Depression & Anxiety: In a 2007 study of 60 patients suffering from mild to moderate depression, rhodiola extract was shown to significantly improve depression markers such as insomnia, self-esteem and emotional stability when compared to placebo. Similar improvements have been noted in studies and in practitioner feedback when examining the benefits on generalized anxiety disorder. Clinically, many practitioners recommend rhodiola to patients that present as “wired and tired”, meaning anxious and on edge, yet exhausted.
How Does Rhodiola Work in the Body?
Research has found that one of the ways in which rhodiola positively impacts the mental health of an individual is through the balancing of neurotransmitters, chemicals in the brain that are responsible for regulating mood. Rhodiola specifically prevents the breakdown of adrenaline, serotonin, dopamine and acetylcholine, thereby increasing their action in the brain. This ultimately improves cognitive measures such as mood, memory and attention.
Although there are many active ingredients within the whole plant extract, rosavins appear to hold most of the medicinal power. With this in mind, it is important to select a rhodiola supplement that specifies the rosavin content.
But is Rhodiola Safe?
Yes, rhodiola is extremely safe for the vast majority of the population. However, pregnant women, nursing mothers and those diagnosed with bipolar disorder should avoid or consult with a qualified healthcare practitioner before beginning supplementation.
In the end, rhodiola root is a great option for those feeling stressed or overwhelmed. Whether high stress in your life leads to poor sleep, depressed mood, low energy or even recurring colds and flus, rhodiola may be that missing piece to help get you out of your slump. Everyone needs support from time to time and rhodiola can be the much-needed crutch during a busy transition!
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