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Why Use L-Theanine in Your Practice?

Posted April 18, 2019

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.

 


References:

[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.

 

Targeting the Mighty Mitochondria in Clinical Practice

Posted March 19, 2019

By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix

The role of mitochondrial dysfunction in chronic and degenerative diseases is becoming more and more evident. Although the basic function of the mitochondria is to create cellular energy and remove waste byproducts, these are complex tasks with countless areas of potential error. If problems exist in the mitochondria, your patient’s symptoms will reflect this. Clinically, patients with mitochondrial stress present with low energy and especially poor recovery from exertion or environmental stressors, similar to a poor adrenal response.

In addition to foundational nutrients such as magnesium and B-vitamins, a number of nutrients have been identified to specifically improve mitochondrial function and clinical outcomes:

 

  •      Acetyl-L-Carnitine (ALC): ALC is the acetylated form of L-Carnitine and the only form demonstrated to cross the blood-brain-barrier and enter the central nervous system. Research has shown that ALC can improve various markers of cognition and mood, including attention, reaction time, memory, depression and mental fatigue.[i] [ii] ALC also protects the nerves in cases of drug-induced neuropathy and diabetic neuropathy, with extensive evidence to show that it can positively impact sperm motility and, thereby, male infertility. [iii] [iv]

 

  •      N-Acetyl-Cysteine (NAC): NAC is the rate-limiting amino acid needed to build glutathione, our body’s master antioxidant. This ability to upregulate glutathione explains why it is conventionally used to protect the liver in cases of acetaminophen toxicity and why it is known as a liver protectant and detoxifying agent. It has powerful antioxidant actions which may help to explain why it can reduce acne severity, stabilize mood in bipolar patients and reduce miscarriage rates in women.[v] [vi] [vii] Finally, NAC is an effective and well-researched mucolytic agent in cases of bronchitis and other respiratory conditions.[viii]

 

  •      Coenzyme Q10 (CoQ10): CoQ10 is another powerful antioxidant within the body that is necessary for cellular energy production in the electron transport chain. Although CoQ10 is most well-known for its ability to improve cardiovascular conditions such as congestive heart failure, cardiomyopathies and hypertension[ix] [x], clinical trials have also shown that supplementation can improve Parkinson’s disease[xi], sperm parameters and male infertility[xii], oocyte quality and female infertility[xiii], migraines[xiv] and more.

 

  •      Alpha Lipoic Acid (ALA): ALA is another nutrient that has demonstrated the ability to protect the nervous system and improve mitochondrial function. ALA is capable of increasing both intracellular glutathione levels and coenzyme Q10 levels, making it the ideal nutrient to supplement alongside NAC and CoQ10.[xv] ALA has specifically been studied for its ability to reduce blood sugars, protect nerve cells, reduce pain, numbness and burning in cases of diabetic neuropathy and chelate heavy metals such as mercury. [xvi]

 

  •      Pyrroloquinoline Quinone (PQQ): This B-vitamin like compound helps to protect neurons from toxicity, to enhance nerve growth factor (NGF) production and prevent memory deficits related to free radical damage.[xvii]  These actions are enhanced through the concomitant use with CoQ10 and, collectively, they have been shown to protect the mitochondria and activate the generation of new mitochondria. [xviii] Although clinical research is less robust than other mitochondrial nutrients, animal studies with PQQ are intriguing in that they have demonstrated peripheral nerve regeneration and myelin repair.[xix]

 

Collectively, these ingredients can help to restore mitochondrial function to the cellular powerhouse that it should be. Mitochondrial support should be considered for all patients with cognitive dysfunction, low energy, nerve damage, fertility concerns, chemical sensitivities or poor recovery from environmental stressors.

Often targeted mitochondrial nutrients can be beneficial when used concomitantly with adrenal support or in cases where adrenal supportive nutrients do not provide clinical benefit. In particular, mitochondrial nutrients are indicated for individuals with toxin exposure and resultant cellular detoxification deficits. 

 


References:

[i] Arch Gerontol Geriatr. 2008 Mar-Apr;46(2):181-90.

[ii] Psychosom Med. 2004 Mar-Apr;66(2):276-82.

[iii] PLoS One. 2015; 10(3): e0119479

[iv] Iran J Reprod Med. 2012 Mar; 10(2): 77–82.

[v] J Clin Exp Dermatol Res 2012, 3:5

[vi] Int J Bipolar Disord. 2018; 6: 11

[vii] Reprod Biomed Online. 2008 Nov;17(5):722-6.

[viii] European Respiratory Review 2015 24: 451-461

[ix] Open Heart 2015;2:e000326

[x] J Hum Hypertens. 2007 Apr;21(4):297-306

[xi]  Arch Neurol 2002;59:1541-1550

[xii] Int Urol and Nephrol. 44(3):689-700

[xiii] Aging Cell. 2015 Oct; 14(5): 887–895.

[xiv]  Cephalalgia 2002;22:137-141

[xv] Alt Med Review 2006; 11(3)

[xvi] Int J Endocrinol. 2012; 2012: 456279.

[xvii] Food Style 2009; 21: 13(7): 50-3.

[xviii] Alt Med Review 2009; 14(3):268-277

[xix] Microsurgery. 2005;25(4):329-37.

 

Vitamin K2: An Unsung Hero for Cardiovascular Health

Posted February 1, 2019

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.

 


References:

[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

Lesser Known Interventions for Reducing Food and Sugar Cravings

Posted December 13, 2018

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:

  1.   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.
  1.    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.
  1.    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.
  1.    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.
  1.    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?

 


 

References:

[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.

 

 

Beyond Sleep: The Surprising Benefits of Melatonin

Posted October 18, 2018

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.

 


 

References:

[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 3mg, amitriptyline 25mg 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.

An Orthomolecular Approach to Mental Health

Posted September 18, 2018

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.”

 


 

References:

[1]  Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C (2017) Role of magnesium supplementation in the treatment of depression: A
randomized clinical trial. PLoS ONE 12(6).

[2]  Rajizadeh, Afsaneh et al. Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A
randomized, double-blind, placebo-controlled trial. Nutrition, Volume 35, 56 – 60.

[3]  Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70. Epub 2006 Mar 20.

[4]  Levenson CW. Zinc: the new antidepressant? Nutr Rev. 2006 Jan;64(1):39-42.

[5] 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.

[6] 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.

[7] Nowak G, Szewczyk B, Pilc A. Zinc and depression. An update. Pharmacol Rep. 2005 Nov-Dec;57(6):713-8.

[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.

[9] Almeida OP, Ford AH, Hirani V, Singh V, vanBockxmeer FM, McCaul K, Flicker L. B vitamins to enhance treatment response to antidepressants in
middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial. Br J Psychiatry. 2014 Sep 25.

[10] Vulser H et al. Association between depression and anemia in otherwise healthy adults. Acta Psychiatr Scand. 2016 Aug;134(2):150-60.

[11] Stewart R and Hirani V. Relationship between depressive symptoms, anemia, and iron status in older residents from a national survey
population. Psychosom Med. 2012 Feb-Mar;74(2):208-13.

[12] Maddock J, Berry DJ, Geoffroy MC, Power C, Hypponen E. Vitamin D and common mental disorders in mid-life: cross-sectional and prospective
findings. Clin Nutr. 2013 Jan 21.

[13] Bahrami A et al. High Dose Vitamin D Supplementation Is Associated With a Reduction in Depression Score Among Adolescent Girls: A Nine-
Week Follow-Up Study. J Diet Suppl. 2017 Jul 31:1-10.

[14] Vaziri F et al. A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers. BMC
Pregnancy Childbirth. 2016 Aug 20;16:239.

[15] Jorde R et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind
trial. J Intern Med. 2008 Dec;264(6):599-609.

[16] Gowda U et al. Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition. 2015
Mar;31(3):421-9.

[17] Su K, Tseng P, Lin P, et al. Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms: A
Systematic Review and Meta-analysis. JAMA Network Open.2018;1(5):e182327. doi:10.1001/jamanetworkopen.2018.2327.

[18] Appleton KM, Gunnell D, Peters TJ, Ness AR, Kessler D, Rogers PJ. No clear evidence of an association between plasma concentrations of n-3
long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population. Prostaglandins Leukot Essent Fatty Acids. 2008
Jun;78(6):337-42.

[19] Rapaport MH et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-
concept study. Mol Psychiatry. 2016 Jan;21(1):71-9.

[20] Benton D. Selenium intake, mood and other aspects of psychological functioning. Nutr Neurosci. 2002 Dec;5(6):363-74.

Rethinking Protein Supplementation in your Practice

Posted August 20, 2018

By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix

It’s easy to think of protein supplementation when patients are concerned about athletic performance and muscle recovery. Of course, protein is extremely useful in these circumstances, yet the many other clinical indications often get overlooked. Protein is a macronutrient that should be considered as a foundational item in all of our treatment protocols.

Improving dietary protein intake is key. But many times, a high-quality protein supplement is useful adjunctively. The purpose of this article is not to say that everyone should be supplementing with protein, more so, to say that there are likely other circumstances that you could be considering its impact. Here is a brief refresher on when to consider a high-quality protein with your patients:

 

  • Liver Health: Whey protein is a rich source of cysteine, making it a viable option to increase glutathione production and, therefore, liver detoxification. Research has confirmed this and also shown that protein supplementation improves outcomes in individuals with liver cirrhosis and those with non-alcoholic steatohepatitis (NASH).[1] [2]
  • Blood Sugar Regulation: Protein, unlike carbohydrates, does not significantly raise blood sugars in individuals with adequate insulin levels.[3] In fact, substituting protein in for carbohydrates or other macronutrients may lead to better blood sugar regulation in both diabetics[4] and non-diabetics.[5]  
  • Pre-eclampsia: Weak evidence suggests that the edema and protein spilling in pre-eclampsia is as a result of low protein intake, breaking down tissues to provide the fetus with needed amino acids. Although research appears to be far from conclusive, extra protein is a simple and safe intervention.[6]
  • Weight Management: High protein meals, especially at breakfast, have been shown to increase satiety and reduce snacking, making protein supplementation a staple for those trying to lose weight or manage dietary cravings.[7] [8]
  • Post-surgery Recovery: Regardless of the complexity or invasiveness of the procedure, surgery is a significant stress and physical trauma to the body. This means that protein is required for recovery. Evidence shows that protein is beneficial not only on the days after surgery but also in preparation for the operation.[9] [10]
  • Hair Loss: Yes, thyroid function, iron, biotin, medication side effects and other factors need to be considered for hair loss, but protein is a core component of collagen and a core component of hair. Most women trying to solve hair loss on their own likely don’t consider protein levels as a key first step.[11]
  • Sports Performance: It is still worth mentioning that protein supplementation added to a resistance training or endurance program has the ability to stimulate anabolism in muscles with increased hypertrophy, improved strength and reduced recovery time.[12] [13]
  • Bone Health: Protein is necessary for building collagen in the bone matrix. Multiple studies have shown that protein supplementation improves fracture healing, bone mineral density and overall recovery from injury.[14] [15]
  • Mood Balancing: Protein contains all the amino acid building blocks for our key neurotransmitters like dopamine, GABA and serotonin. Moreover, anecdotal and preliminary evidence shows that specific amino acids, like taurine, can be beneficial for balancing mood.[16] A common concern in poorly managed vegan or vegetarian patients is low mood, and suboptimal protein intake can be a part of this problem in conjunction with low iron and B12.

 

Certainly, this is not an all-encompassing list of reasons to consider protein supplementation with your patients, but it should serve as a reminder, at the very least, to assess macronutrient intake and be cognizant of the tremendous impact that suboptimal protein intake can have on the body long-term!


References:

[1] Hirsch S et al. Nutritional support in alcoholic cirrhotic patients improves host defenses. J Am Coll Nutr. 1999 Oct;18(5):434-41.

[2] Chitapanarux T et al. Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients. J Gastroenterol Hepatol. 2009 Jun;24(6):1045-50. doi: 10.1111/j.1440-1746.2009.05865.x.

[3] Franz MJ. Protein: metabolism and effect on blood glucose levels. Diabetes Educ. 1997 Nov-Dec;23(6):643-6, 648, 650-1.

[4] Mary C Gannon, Frank Q Nuttall, Asad Saeed, Kelly Jordan, Heidi Hoover; An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes, The American Journal of Clinical Nutrition, Volume 78, Issue 4, 1 October 2003, Pages 734–741, https://doi.org/10.1093/ajcn/78.4.734

[5] Rains TM et al. A randomized, controlled, crossover trial to assess the acute appetitive and metabolic effects of sausage and egg-based convenience breakfast meals in overweight premenopausal women. Nutr J. 2015 Feb 10;14:17. doi: 10.1186/s12937-015-0002-7.

[6] James M. Roberts, Judith L. Balk, Lisa M. Bodnar, José M. Belizán, Eduardo Bergel, Anibal Martinez; Nutrient Involvement in Preeclampsia, The Journal of Nutrition, Volume 133, Issue 5, 1 May 2003, Pages 1684S–1692S, https://doi.org/10.1093/jn/133.5.1684S

[7] Heather J Leidy, Laura C Ortinau, Steve M Douglas, Heather A Hoertel; Beneficial effects of a higher-protein breakfast on the appetitive, hormonal, and neural signals controlling energy intake regulation in overweight/obese, “breakfast-skipping,” late-adolescent girls, The American Journal of Clinical Nutrition, Volume 97, Issue 4, 1 April 2013, Pages 677–688, https://doi.org/10.3945/ajcn.112.053116

[8] Skov AR et al. Randomized trial on protein vs carbohydrate ad libitum fat reduced diet for the treatment of obesity. Int J Obes 1999; 23:528-536

[9] Herbert Freund et al. Infusion of the Branched Chain Amino Acids in Postoperative Patients: Anticatabolic Properties. Ann Surg. 1979 Jul; 190(1): 18–23.

[10] Klein JD et al. Perioperative nutrition and postoperative complications in patients undergoing spinal surgery. Spine (Phila Pa 1976). 1996 Nov 15;21(22):2676-82.

[11] Rushton DH. Nutritional factors and hair loss. Clin Exp Dermatol. 2002 Jul;27(5):396-404.

[12] Cooke et al. Whey protein isolate attenuates strength decline after eccentrically-induced muscle damage in healthy individuals. J Int Soc Sports Nutr. 2010 Sep 22;7:30. doi: 10.1186/1550-2783-7-30.

[13] Cermak et al. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr. 2012 Dec;96(6):1454-64. doi: 10.3945/ajcn.112.037556. Epub 2012 Nov 7.

[14] Chiu JF, Lan SJ, Yang CY, Wang PW, Yao WJ, Su LH, Hsieh CC. Long-term vegetarian diet and bone mineral density in postmenopausal Taiwanese women. Calcif Tissue Int. 1997 Mar;60(3):245-9.

[15] Tengstrand B et al. Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture. Clin Nutr. 2007 Aug;26(4):460-5. Epub 2007 May 11.

[16] Gao-Feng Wu et al. Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats. Sci Rep. 2017; 7: 4989. Published online 2017 Jul 10.

The Role of Antioxidants in Sun Protection

Posted July 5, 2018

By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix

The sun is shining and summer is officially here! This is great news for many of us Canadians that find the winters to always be a bit too long…but it’s not so great for our skin health if we aren’t well prepared.

Proper sunscreen application, skin coverage and avoidance of direct sun during peak UV hours (11am-3pm) are all important factors when it comes to sun safety and reducing your risk of sunburn and skin cancer. But few people acknowledge the role of diet and antioxidant protection in sun protection. What we put in our bodies matters, too.

For example, excessive alcohol consumption has been correlated with higher rates of sunburn, and interventional evidence confirms that alcohol consumption reduces the time it takes for your skin to become red after UV exposure. Essentially, alcohol decreases the efficiency of our antioxidant network in the skin, thereby decreasing the protection from UV rays. Not such great news for patio beers and summer drinks on the dock.

This all makes sense, though, when you consider that tanning or becoming sunburnt is simply damage caused by ultraviolet rays. Our skin darkens to naturally protect against future exposure to these same UV rays. As this process is occurring, tons of free radicals are produced in the body that need to be quenched. Antioxidants to the rescue!

In addition to a diet high in antioxidants and bioflavonoids from fruits and vegetables, specific natural health ingredients have been targeted and identified as beneficial for sun protection. Consider the following antioxidants for extra support:

 

  • Cocoa: As if you need more reason to consume regular amounts of dark chocolate, research has shown that a daily cocoa powder drink led to less redness after UV exposure at 6 and 12 weeks. Improved hydration and circulation of the skin was also noted in those consuming the flavanol-dense cocoa drink but not those in the control group.
  • Vitamin C and E: Multiple studies have explored the effects of these commonplace anti-oxidants in UV protection. It turns out that both topical application of vitamin C and oral supplementation of vitamin C in combination with vitamin E can provide numerous benefits. One study explored an oral combination of vitamin C, vitamin E, selenium, carotenoids and proanthocyanidins, finding that the blend led to a decrease in matrix metalloprotease levels after UV exposure, possibly explaining part of the mechanism involved in antioxidant photoprotection.
  • Carotenoids: Various carotenoids, alone and in combination, have shown promise for UV protection. A double-blind placebo-controlled trial of 20 women found that 30mg of beta-carotene per day, for 10 weeks prior to 13 days of sun exposure, led to less skin redness. Another study of 24mg of Beta-Carotene, in combination with 8mg Lutein and 8mg Lycopene showed benefit. A combination of lutein and zeaxanthan, orally and topically, also show benefits. Two poorly done studies found that mixed carotenoids allowed for greater tolerability of the sun and more time until redness ensued. It should be noted that other studies have found limited or no benefit for sun protection with carotenoids, but the vast majority show benefits.
  • Green Tea Extract: Although animal research and human study have only shown benefits for the topical application of green tea and its constituents, it stands to reason that regular oral consumption of the anti-oxidant powerhouse tea would be a good idea for the prevention and treatment of sun damage, too. At the very least, daily intake of green tea can be used to promote optimal metabolism and perhaps replace other bad habits!
  • EPA Omega-3 Fatty Acid: In a double-blind randomized study, either 4 grams/day of EPA or 4 grams/day of oleic acid was supplemented for 3 months. After 3 months of supplementation, those in the EPA group had an 8-fold increase in EPA skin content and, most importantly, significantly reduced sunburn sensitivity (meaning a greater resiliency or threshold until burning). Markers of DNA damage in the skin were also reduced.  

 

Animal research, anecdotal evidence and mechanistic data suggests that there are many other antioxidants to consider for UV protection of the skin such as astaxanthin, CoQ10 and resveratrol. Preliminary research also indicates that nicotinamide, a form of vitamin B3, is photoprotecive as well, and that quercetin and rutin may be effective when used topically. The recurring theme is antioxidant support and it seems that a blend is best. If you’re headed to the beach, be sure to get your fruits and veggies in!

A Final Note on Sunscreens: When it comes to sunscreens, it is important to mention that they are not all created equal. Here is a quick summary of what to look for in a sunscreen:

  1. Avoid retinyl palmitate and oxybenzone, as these compounds have been associated with hormone disruption and carcinogen activity
  2. Ensure there are active ingredients such as zinc oxide, titanium oxide, avobenzone and mexoryl SX.
  3. Choose lotions instead of sprays

Check out the Environmental Working Group (ewg.org) for more info.


References: 

[1] Mukamal KJ. Alcohol consumption and self-reported sunburn: a cross-sectional, population-based survey. J Am Acad
Dermatol. 2006 Oct; 55(4): 584-9.
[2] Darvin ME et al. Alcohol consumption decreases the protection efficiency of the antioxidant network and increases the risk of
sunburn in human skin. Skin Pharmacol Physiol.2013; 26(1): 45-51.
[3] Heinrich U, Neukam K, Tronnier H et al. Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced
erythema and improves skin condition in women.J Nutr.2006;136:1565-1569
[4] Traikovich SS. Use of topical ascorbic acid and its effects on photodamaged skin topography.Arch Otolaryngol Head Neck
Surg.1999;125:1091-1098.
[5] Eberlein-Konig B, Placzek M, Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-
alpha-tocopherol (vitamin E).J Am Acad Dermatol. 1998;38:45-48.
[6] Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using
solar simulated radiation.Free Radic Biol Med.1998;25:1006-1012.
[7] Greul AK, Grundmann JU, Heinrich F, et al. Photoprotection of UV-irradiated human skin: an antioxidative combination of vitamins
E and C, carotenoids, selenium, and proanthocyanidins.Skin Pharmacology and AppliedSkin Physiology.2002;15:307-315.
[8] Gollnick HPM, Hopfenmuller W, Hemmes C, et al. Systemic beta carotene plus topical UV sunscreen are an optimal protection
against harmful effects of natural UV-sunlight: results of the Berlin-Eilath study.Eur J Dermatol. 1996;6:200-205.
[9] Heinrich U, Gartner C, Wiebusch M, et al. Supplementation with beta-carotene or a similar amount of mixed carotenoids protects
humans from UV-induced erythema.J Nutr. 2003;133:98-101.
[10] Palombo P, Fabrizi G, Ruocco V, et al. Beneficial long-term effects of combined oral/topical antioxidant treatment with the
carotenoids lutein and zeaxanthin on human skin: a double-blind, placebo-controlled study.Skin Pharmacol Physiol.2007;20:199-
210.
[11] Lee J, Jiang S, Levine N, et al. Carotenoid supplementation reduces erythema in human skin after simulated solar radiation
exposure.Proc Soc Exp Biol Med. 2000; 223:170-174.
[12] Stahl W, Heinrich U, Jungmann H, et al. Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced
erythema in humans.Am J Clin Nutr. 2000;71:795-798.
[13] Garmyn M, Ribaya-Mercardo JD, Russel RM, et al. Effect of beta-carotene supplementation on the human sunburn reaction.Exp
Dermatol.1995;4:104-111.
[14] Katiyar SK, Elmets CA, Agarwal R, et al. Protection against ultraviolet-B radiation-induced local and systemic suppression of contact
hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols.Photochem Photobiol.1995;62:855-861.
[15] Elmets CA, Singh D, Tubesing K, et al. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols.J Am Acad
Dermatol.2001;44:425-432
[16] Lesley E. et al. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An
assessment of early genotoxic markers,Carcinogenesis Vol 24(5); 2003: 919–925.

[17] Damian DL. Photoprotective effects of nicotinamide. Photochem Photobiol Sci.2010 Apr;9(4):578-85.
[18] Choquenet B et al. Quercetin and rutin as potential sunscreen agents: determination of efficacy by an in vitro method. J Nat
Prod.2008 Jun; 71(6): 1117-8.