Try this, come back, and we’ll see

Creating great treatment plans

Anew patient – let’s call her Joanna – recently mentioned that she’d been to another practitioner, but had decided to try her luck elsewhere. Her reason?

“She told me to ‘Try this, come back, and we’ll see.’”

At fi rst glance, this might not seem like much of a reason to abandon a doctor. After all, much of what is done in practice is… well, practice. Being 100% confi dent is a luxury we rarely have. “Try this and we’ll see,” simply isn’t that uncommon.

But what Joanna was upset about was not the lack of surety, or the possibility that her care was a bit of an experiment. She simply felt that there was no plan.

And she was right. Try this and we’ll see isn’t a treatment plan any more than one line on a page is a novel. Yet it’s surprisingly common.

Much of the reason stems from putting too much emphasis on treatments. e tools of our trades are deceptive – it’s easy to believe that what you do as a practitioner is about the needles or the herbs or the supplements. But an acupuncture treatment isn’t a plan. Nor is a homeopathic remedy or a supplement. ey’re treatments, not plans. And how they’re used is a prescription, not a plan.

Joanna had a prescription and it wasn’t enough. So what was she missing?

Why Plans Are Important Joanna was craving a plan. A way to understand her treatment in a larger time frame, and how it fi ts in with her symptoms and overall health. And she’s not alone. Patients love plans. Here’s why:

Plans Create Context

Joanna’s not an outlier. She might have been better at articulating her desire for a treatment plan, but she’s not alone in her desire to have one. Patients crave context for their treatment. It’s how they understand that they’re on a path from A to B, and how they manage the anxiety around their health and care.

Even if they’re terrible at making a plan for themselves, patients love when you make one.

They Help Results

The simple act of mapping out treatment seems to have a placebo eff ect of its own. It gives patients a sense that they’re in capable hands, on a journey with a clear route and destination.

Plans Demonstrate Progress

Care takes time. Not everything resolves overnight, particularly chronic complaints that are built over years. A plan provides the context for seeing the slow, steady progress that can be invisible at times.

They Help Create Successful Outcomes

Plans make for commitment, commitment helps compliance, compliance creates success, and success makes more of itself. Want better results? Make a better plan.

What a Good Plan Looks Like

From the patient perspective, a good plan is a clear map from where the patient is to where she wants to be. It’s a health care road trip, with a clear destination, a route and waypoints along the way.

Here are the key high points your plan should hit:

Goals

What are you trying to accomplish? Are you sure you know what success looks like? Better still: does your patient know? Ask them what success looks like for them and make sure you’re on the same page.

Measurement

How will you know when you get to success? What can you measure that will let you know when you’ve arrived, and whether or not you’re headed in the right direction? Objective testing isn’t just a diagnostic tool for doctors – it’s a marker for progress that is hugely benefi cial for patients.

Visit Frequency

Return visits matter, and for more than just treatment – they’re how you track the progress of the plan. But visit structure and rationale are particularly important to clarify for consult-based care.

It’s easy for patients to know why they should come back for their next acupuncture treatment: to get the treatment. But the importance of a follow-up consult may need more clarity. Clearly state the visit structure, and the why behind it.

Tools and Techniques

What are you using to get from where you are now, to where you want to be? is is the area we tend to be best at, but have you explained to your patient why you’re using the modalities you are?

Timelines

What are the timelines? How long until your patient will see results? How long until she reaches success?

Alternatives

What are the options if the proposed plan doesn’t seem to be working? At what point do you consider them? Why are they alternatives, and not part of the active plan?

Even the Best-Laid Plans

Planning is surprisingly easy, but also surprisingly prone to three key pitfalls.

1. Believing ere’s not Enough Time to Plan

It’s easy to think that describing a treatment plan this way is too complicated to work through in an already-crowded visit.

But don’t be fooled. Joanna’s plan, properly laid out, takes just a few moments to communicate. Not a huge investment given the potential return.

The following example might take two, perhaps three, minutes to clearly explain to a patient:

I suspect the root of your problem is a food intolerance. It’s creating a chronic infl ammatory response in your body and your digestive track. at result is a magnesium defi ciency, and that’s what’s causing your migraines.

We’re going to remove your reactive foods from your diet, and see you once a we ek for the next 4-8 weeks for IV magnesium to treat the headaches. If the treatment works, we’ll decrease to once a month treatments after that for a year.

If we’re on the right track, you’ll notice a diff erence within the next 4 weeks, but it’s likely going to take 10-12 months for you to fully recover.

CRP, which is a measure of infl ammation, is elevated in your blood. We’ll measure this every 3 months to make sure it’s decreasing. We’ll follow up every 3 months to discuss the lab result, monitor your symptoms and tweak your treatment plan as needed.

2. Not Sharing the Plan e most common planning pitfall among doctors is that they already think they have a plan. And to be fair, you probably do.

You just might have neglected to tell your patient.

It’s easy to forget that your knowledge and experience make most aspects of the treatment plan seem obvious. So obvious that you don’t need to mention them. Remember, though, that your patient is a) not an expert and b) possibly overwhelmed with everything else you’ve told them during their visit. ey likely can’t create the plan themselves. at’s why they’ve come to you.

3. Too Much Information

Don’t confuse plans with information. A binder full of recipes, handouts and information sheets isn’t a plan – it’s just more information, and if anything it makes it harder for patients to understand and embrace the larger context of their care.

Plans are about broad strokes. ey’re about how to get from Toronto to Vancouver, not about tire pressure or the price of gas. Err on the side of over-simplifi cation. State the obvious, briefl y and clearly. en state it again if you need to.

Plans Help Everyone

A great plan is good for you and your patients. It leads to higher success rates, greater patient satisfaction, and as a result, more referrals.

Used properly, great treatment plans can help you fi nd that unique junction where benefi ts to patient, practitioner and practice overlap – the sweet spot of professional success.

Losing patients? Try better planning. Need more referrals? Try better planning. Want to feel more confi dent about your professional skills? You guessed it…better planning.

Cognitive Behavioural Therapy

Application in clinical practice

Most health practitioners are aware of cognitivebehavioural therapy (CBT). CBT is one of the most studied and most relevant treatments in psychotherapy, with very positive research outcomes. It is short term, focused in the present, and evidence based. Cognitive-behavioural techniques can be quite specifi c but they are also highly adaptable, making them an important component of many diff erent treatment approaches and applicable in a variety of conditions. CBT is well established as a core treatment for many psychiatric disorders (Butler 2006); however, the usefulness of CBT is not limited to mental health concerns. CBT has been shown to reduce distress and improve outcomes related to a number of medical conditions, including chronic fatigue (Malouff 2007), type 2 diabetes (Gonzalez 2009), HIV (Safren 2009), and cancer (Osborn 2006). Cognitivebehavioural therapies can also be applied to help a healthy person optimize their wellbeing. Using CBT to identify and challenge the specifi c belief systems that perpetuate disturbance can help to both shift physiologic experience and promote self-empowerment. ese goals are inherently a part of our naturopathic philosophy and an expression of the mind-body connection.

The CBT Story:

A psychiatrist named Aaron Beck, MD first presented CBT as a specific treatment for depression in the early 1960s. Trained as a psychoanalyst, Dr. Beck began noticing how particular streams of negative thought became active during therapy with depressed patients. Recognizing that these thoughts were not consciously derived or acknowledged, Dr. Beck termed them “automatic negative thoughts.” Dr. Beck also noticed that automatic negative thoughts tended to relate to unconscious beliefs in one of three areas: negative beliefs about oneself, negative beliefs about the future, and negative beliefs about the world. Rather than working through these streams from a strictly psychoanalytic perspective, Dr. Beck began developing tools to help patients directly identify and evaluate the content of their thoughts. By bringing conscious awareness to these automatic and unconscious beliefs, Dr. Beck was able to help his patients begin to think more realistically. As patients began to consciously shift their thinking patterns, they began to feel better emotionally and were able to behave in more effective ways.

From these beginnings, an evidence base spanning 50 years of research has challenged CBT to grow as a treatment modality. CBT has been specifically studied as a treatment for depression and other mood disorders, anxiety disorders, eating disorders, addictions, recovery from trauma, and in the treatment of many medical conditions (for detailed list see Beck Institute 2011). Current research continues to examine the efficacy of CBT in a variety of mental health conditions (Hofmann 2008, McCarthy 2007, Roberts 2009) as well as its role in mindfulness-based therapy (Hofmann 2010) and healthy psychological adjustment in non-clinical populations. With such a rich research history behind it, contemporary data on CBT has become increasingly refined. For example, Cape and colleagues (2010) evaluate the use of a brief-form CBT in primary care as a treatment for anxiety, depression, and mixed mood disorders. Hart and Hart (2010) consider the values and limitations of CBT in a behavioural medicine context. Another interesting perspective (Spek 2007) explores the use of internetbased CBT and alternate delivery forms that make CBT tools much more widely accessible. Although the literature will continue to evaluate and critique the clinical parameters of CBT, its value as a psychotherapeutic tool is evident.

Next Steps: With an abundance of data to draw from and clear indications for the use of cognitive-behavioural therapies, the next question is how a naturopathic doctor can utilize the resources provided by a CBT model. Even without specific training in CBT, there are practical ways that an ND can apply cognitive-behavioural principles within a naturopathic context. While cognitivebehavioural methods may be of particular interest to those who treat patients with anxiety and depression, it is important to remember that these tools are much more broadly applicable. If we consider maladaptive belief systems as an obstruction to Vis, then we can begin to understand how beneficial cognitivebehavioural restructuring can be with regards to overall health. Recent advances in the science of epigenetics demonstrate how deeply organizing our perceptual systems are with regards to our physiology. In his work on the biology of belief (Lipton 2005), Dr. Bruce Lipton, PhD, explains how perception mediates cellular behaviour and biological expression. Our core beliefs and perceptual habits exert a significant influence on cellular behaviour and are strong epigenetic regulators. Informed by this perspective, we can begin to harness the restorative biological power that comes with increased freedom from cognitive distortions and limiting beliefs.

There is not just one way to use CBT in a naturopathic practice. For people who prefer a more structured and linear approach, there are some great resources on the market that will take you through the process step by step. For practitioners who would like to integrate a more general use of cognitive-behavioural therapy within a naturopathic framework, I will offer some suggestions as to what this might look like. The most important components of any cognitive-behavioural therapy include the capacity for self-reflective awareness, learning to identify specific thought patterns, and restructuring maladaptive belief systems. NDs can implement a cognitive-behavioural approach to health by helping patients to first become more aware of their thoughts and then learn to observe them without reacting to them. The goal here is to identify specific words, expectations, and assumptions that have a negative influence on a person’s wellbeing and to understand the context in which those thoughts become active.

Begin by noticing if there are certain words that a patient frequently uses to describe themselves, their life situation, or their relationships. What words have adverse energy for that person and in what context? Do the automatic negative thoughts tend to be active in all domains of life or are they more prevalent with regards to the way a person views a specific aspect of their life? (eg: self-image, home, work, relationships, family, health, finances, etc). What automatic assumptions are attached to those thoughts? How do those thoughts impact the person’s emotional state? Their body sensations? Their relationships? Their behaviours? By consciously identifying automatic negative thoughts and describing their impact on other aspects of experience, patients are able to begin separating themselves from their thinking and can better see the connections between thoughts, feelings, and behaviours.

As you teach patients to become more aware of their own thought patterns, you can actively challenge negative self-talk within an appointment by reflecting negative thought streams back to patients and asking them to consider the validity of that thought (“I hear you say quite often that you’ll never be healthy; do you believe that is true?” or “I’ve noticed that you tend to put yourself down when you are talking about your family; do you believe that you are less worthy of love than your siblings?”). Once you have identified a problematic thought, you can challenge the patient to discover whether or not that thought is true. Although it may feel 100% true, it often is not. Engage the patient by asking them to give evidence for the truth of a particular thought. Then ask them if there is any evidence that the thought is not completely true. You can expand on this by asking them to consider at least one alternate perspective (“How else might you explain this? What else could it mean?”). This kind of therapeutic conversation challenges patients to begin questioning and changing their cognitive habits.

Thought records are another way to help patients develop self-reflective awareness and learn to identify cognitive patterns. Patients are asked to track their thoughts, writing them down each time they become aware of them throughout the day. There are many resources available for learning to keep thought records, and essentially they all teach people to notice and evaluate their self-talk. Many thought records also include instructions on how to identify and label automatic negative thoughts (for example, is this thought a catastrophizing thought? A “should” thought? An all-or-nothing thought?), as well as how to create a habit of thinking more realistically (eg: changing “I’m never good at anything” to “even though I didn’t do as well as I would have liked, I still passed the exam”). Teaching people to become aware of and challenge their thinking can be an empowering step towards change.

Once a person has become more conscious of their self-talk, it is usually fairly simple to see that these automatic negative thoughts cluster around certain themes. As themes begin to appear within the automatic thought patterns, you can track them to underlying core beliefs. For example, automatic negative thoughts could cluster around themes of mistrust, autonomy, shame and guilt, competence, inferiority, perfection, intimacy, protection, or meaning. While there are limitless possibilities as to how these themes express themselves, they typically relate to the ways we view ourselves, the world around us, and our future potentials. Often they have to do with perceptions related to one’s worth as a person, the ability to give/receive love, the expression of power/control, and the desire for acceptance. As we explore the belief systems that motivate our feelings and behaviours, we start to identify perceptual distortions that limit our experience of the world. In homeopathic terms, these can be considered “delusions” and those with a homeopathic mindset will find that they can prescribe on the experience of these themes. The same idea applies to TCM: as you clarify the energy of the belief system you can correlate it with the five elements or mental-emotional patterns of specific organ imbalances and treat accordingly. From this perspective, cognitivebehavioural approaches are not only independent therapeutic tools but also provide a level of understanding that is helpful when applying other treatment modalities. Prescribing from this level allows for an expression of “treat root cause.” What we are trying to do is isolate belief systems that perpetuate disturbance in physiology, psychology, and behaviour. In other words, the belief system itself is pathogenic and once we understand its role, we can apply any of our naturopathic modalities to help correct it.

Belief systems create the perceptual configurations for the experience of life. As these belief systems become more visible, a range of options opens up to you and you can actively engage in a restructuring process. You can recognize the origins of some beliefs (“my father told me that winning is the only thing that matters”) and with compassion begin to let them go. You will find that some beliefs shift easily and others are much more entrenched. Sometimes it helps to directly challenge the truth of these belief systems and evaluate the data that supports/refutes them, and at other times it is better to just question whether or not the belief is helpful in the present. A good question to ask is, “how does this belief contribute to my health, happiness, and wellbeing?” If the answer is, “it doesn’t” then ask the patient what holds the belief in place, what sustains its presence in their psyche. Evaluate the justifications for keeping the belief and consider the possibilities for releasing it. “Who would I be without this belief” is another good question for discussion.

It is important to remember that cognitive-behavioural tools are most efficacious within a comprehensive and individualized approach to treatment. Some patients may just need direction to available resources and encouragement towards self-study; others may appreciate a workbook-style approach where you work as a team. Some patients may respond well when you engage in therapeutic conversation around a belief, allowing them to recognize it for themselves and encouraging them to examine the patterns in place around that belief in their lives. Some patients will enjoy a cognitively-oriented approach to working with belief systems but others may benefit from focusing more on the emotions, images, or sensations associated with the belief. Other people will do best when they are behaviourally-oriented. Understanding your patient as an individual keeps you true to the philosophy of naturopathic medicine and it also allows you to customize treatment so that it is as effective as possible. Whether you are drawn to a more cognitive approach to CBT or if you can better relate to cognitive work through another form like homeopathy, guided imagery, TCM, or body-based therapies, there are many ways that our profession can serve others through responsible use of functional psychotherapy.

References:

Beck Institute. www.beckinstitute.org Accessed January 2011.

Butler AC, Chapman JE, Forman EM, Beck AT. The empirical status of cognitive-behavioral therapy: a review of meta-analyses. Clin Psychol Rev. 2006 Jan;26(1):17-31.

Cape J, Whittington C, Buszewicz M, Wallace P, Underwood L. Brief psychological therapies for anxiety and depression in primary care: meta-analysis and meta-regression. BMC Med. 2010 Jun 25;8:38.

Gonzalez JS, McCarl LA, Wexler DJ, Cagliero E, Delahanty L, Soper TD, Goldman V, Knauz R, Safren SA. Cognitive behavioral therapy for adherence and depression (CBT-AD) in type 2 diabetes. Journal of Cognitive Psychotherapy. 2010;24(4):329-343.

Hart SL, Hart TA. The future of cognitive behavioral interventions within behavioral medicine. Journal of Cognitive Psychotherapy. 2010;24(4):344-353.

Hofmann SG, Sawyer AT, Witt AA, Oh D. The effect of mindfulness-based therapy on anxiety and depression: A meta-analytic review. J Consult Clin Psychol. 2010 Apr;78(2):169-83.

Hofmann SG, Smits JA. Cognitive-behavioral therapy for adult anxiety disorders: a meta-analysis of randomized placebo-controlled trials. J Clin Psychiatry. 2008 Apr;69(4):621-32.

Lipton, Bruce. The Biology of Belief. 2005. Malouff JM, Thorsteinsson EB, Rooke SE, Bhullar N, Schutte NS. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis. Clin Psychol Rev. 2008 Jun;28(5):736-45.

McCarty CA, Weisz JR. Effects of psychotherapy for depression in children and adolescents: what we can (and can’t) learn from meta-analysis and component profiling. J Am Acad Child Adolesc Psychiatry. 2007 Jul;46(7):879-86.

Osborn RL, Demoncada AC, Feuerstein M. Psychosocial interventions for depression, anxiety, and quality of life in cancer survivors: meta-analyses. Int J Psychiatry Med. 2006;36(1):13-34.

Roberts NP, Kitchiner NJ, Kenardy J, Bisson JI. Systematic review and meta-analysis of multiplesession early interventions following traumatic events. Am J Psychiatry. 2009 Mar;166(3):293- 301.

Safren SA, O’Cleirigh C, Tan JY, Raminani SR, Reilly LC, Otto MW, Mayer KH. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol. 2009 Jan;28(1):1-10.

Spek V, Cuijpers P, Nyklicek I, Riper H, Keyzer J, Pop V. Internet-based cognitive behaviour therapy for symptoms of depression and anxiety: a meta-analysis. Psychol Med. 2007 Mar;37(3):319-28.

CoEnzyme Q10

Cardiovascular applications

Introduction

In 2007, heart disease was one of the two leading causes of death for Canadians and was responsible for 22% of the 235,217 deaths (Statistics Canada 2010). Heart disease includes heart failure, angina, cardiomyopathy, coronary artery disease, valve disorders and other conditions related to the heart. ese staggering numbers call for the best possible treatments for heart disease whereupon Coenzyme Q10 (CoQ10) has appeared as a promising therapy.

Heart Facts e adult human heart weighs from 200 to 425g and is able to convert chemical energy to mechanical energy extremely effi ciently. To put it in numbers, it is capable of pumping out fi ve liters of blood every minute, 7200 liters per day and over 2.6 million liters every year. In order to execute this, the heart hydrolyzes an estimated six kilograms of adenosine-5’-triphosphate (ATP) per day (Soukoulis 2009).

High blood pressure (BP) is one of the most important cardiovascular risk factors worldwide. Approximately two-thirds of patients do not achieve optimal BP control using drug therapy (Yusuf 2004). Other interventions are extremely important, as a reduction of 5mmHg in systolic BP has been associated with a 7% reduction in all-cause mortality (Whelton 2002).

The consequences of heart failure are concerning and despite sophisticated diagnostic techniques and treatments, the risk of death within fi ve years of diagnosis is greater than 50% (Dunn 2009). CoQ10 levels in the blood have been found to be an independent predictor of mortality in congestive heart failure (Molyneux 2008).

About CoQ10

First isolated in 1957 from beef mitochondria, CoQ10, or ubiquinone is highly concentrated in heart-muscle cells due to their increased energy requirements (Crane 1989). In addition to its role in the formation of ATP, CoQ10 serves to delay or prevent lipid peroxidation and enhances cell membrane stabilization (Sarter 2002, Shah 2007). Due to the fact that mitochondria are particularly vulnerable to oxidative damage, mitochondria targeted antioxidants like CoQ10 can be an effective therapeutic strategy in preventing or reducing the progression of cardiovascular and other disorders (Graham 2009).

CoQ10 is mostly found in active organs like the heart where a substantial decline can be observed with increasing age (Pravst 2010). An adult human body has approximately 2 grams of CoQ10 and 0.5 grams must be replaced daily making the average turnover rate in the body around 4 days (Pravst 2010). Human intervention trials have found supplemental CoQ10 to be effective in cardiovascular disorders like cardiomyopathy, hypertension, angina pectoris, atherosclerosis, ischemic heart disease, cardiovascular surgery, hypertension, valvular heart diseases and myocardial infarctions (Hadj 2007, Kumar 2009).

Sources

Common sources for CoQ10 are beef, poultry, broccoli, soya oil, fish oils, peanuts, sardines, and mackerel. However, an average dietary amount of CoQ10 is only 2-6mg/day, which is inadequate to provide levels in the body required to be beneficial in pathological states (Kumar 2009, Pravst 2010).

Metabolism and Excretion

CoQ10 is absorbed from the small intestine and transferred into the blood circulation. It is then carried to the liver where it undergoes biotransformation and is primarily excreted through the bile duct. In this process, only a fraction of the ingested amount is carried to other organs like the heart, adrenal glands, kidneys and lungs (Ozaki 2010, Wyman 2010). Approximately 60% of an oral dose is eliminated in the feces during chronic oral administration and the elimination half-life is about 34 hours (Greenberg 1990). Due to its excretion pathway, patients with biliary obstruction or hepatic impairment may accumulate CoQ10 in their bodies (Ozaki 2010, Wyman 2010).

Absorbability and Dosage

Due to its lipophilic nature, CoQ10 is best absorbed with meals or in emulsified form. Divided dosing also maximizes absorbability while minimizing potential side effects (Ozaki 2010).

What form of CoQ10 is best? According to Hosoe (2007), ubiquinol, the reduced form of CoQ10, is two times more absorbable than ubiquinone. In support of ubiquinol, Langsjoen (2008) found that ubiquinol dramatically improved absorption and was correlated to improvements in CoQ10 levels and positive clinical outcomes that were not possible with the use of ubiquinone at even up to 900mg/ day. However, it has also been reported that the form of CoQ10 ingested may not be so important. According to Pravst (2010), ubiquinone appears to be reduced during or following absorption in the intestine, and as a result more than 95% of CoQ10 in circulation exists in the more active ubiquinol form after its ingestion. Thus, the answer to this question is still in contention.

The recommended daily dose of CoQ10 ranges from 30 to 100mg per day for healthy people (Pravst 2010) or 60 to 200mg per day in treating different conditions (Kumar, 2009). A maximum dosage of 1200mg has recently been suggested for adult intake as it has been found to be well tolerated and safe (Hathcock 2006).

Normal blood levels range from 0.7 to 1.0 ug/ml; doses of 30-60mg can be used to prevent CoQ10 deficiency and to maintain normal serum concentrations. However, clinically useful levels necessitate above normal CoQ10 blood levels that may be two to four times higher. In fact, 450mg of CoQ10 a day was found to achieve a plasma level of 4ug/ml and was much more successful in reversing the course of severe heart failure (Kumar 2009).

These increased levels may take days or months to achieve. Oral administration of 100mg/day of CoQ10 for two to eight months resulted in an increase of 20-85% in myocardial CoQ10 levels in patients with cardiomyopathy (Folkers 1985, Sarter 2002). Due to this slow plasma increase of CoQ10, clinical improvement is normally seen one to four weeks after initiation of treatment and it may take months to reach maximal clinical benefit (Kumar 2009).

Mechanism of action

CoQ10 appears to work in several ways including targeting expression of multiple genes, such as those involved in intermediary metabolism and cell signaling. This gene regulation and control of metabolism may explain many of the cardiovascular and other actions of CoQ10 (Rosenfeldt 2007). The beneficial effect of CoQ10 in hypertensive cases is a result of decreased peripheral resistance that is due to its direct action on the vascular wall. Free radicals inactivate nitric oxide (NO), thus preventing NOmediated relaxation of the smooth muscle layer of the vascular wall. By acting as a free radical scavenger, CoQ10 is able to prevent vasoconstriction and the resulting increase in blood pressure (Ankola 2007). With regards to coronary heart failure and myocardial infarction, CoQ10 is hypothesized to benefit these states through its direct impact on energy production by mitochondria, improving ATP availability for the failing heart (Kumar 2009, Crane 2001).

Side Effects

A long-term noncomparative study was conducted in 173 Italian centers to specifically look at safety and efficacy of CoQ10 in 2664 patients with congestive heart failure (Baggio 1994). In this study, preexisting adverse reactions were taken at baseline and then recorded again after three months of treatment with only 36 patients (1.3%) complaining of side effects mainly to do with mild gastrointestinal upset (Baggio 1994). The maximum dose in this study was 150mg per day. However, CoQ10 supplementation has been found to be free of side effects at dosages up to 600mg/day and well tolerated and safe up to 1200mg/day (Hathcock 2006). Aside from possible abdominal discomfort, nausea, vomiting, diarrhea and anorexia, allergic rash and headache have also been reported in rare cases. It is reported that CoQ10’s antiplatelet effect may increase the risk of bleeding, especially in those on antiplatelet medication (Wyman 2010). However, due to its vitamin K like action it may also act to oppose the anticoagulant effects of warfarin (Jelin 2009).

Clinical evidence

Research for CoQ10 has resulted in many positive conclusions that include Langsjoen’s study published in 1994 illustrating the usefulness of CoQ10 in clinical cardiology. It tested the use of CoQ10 in 424 patients with different types of myocardial diseases. Patients were treated with an average of 240mg of CoQ10 per day and followed an average of approximately a year and a half. Significant improvement in New York Heart Association functional classification (Table 1) was seen. 58% of patients improved by one NYHA class, 28% improved by two classes, 1.2% by three NYHA classes. Within a month, myocardial function became measurably improved. By six months, maximal improvement was usually obtained and this improvement was sustained in the majority of patients. 43% stopped between one and three drugs and only 6% required the addition of one drug. The withdrawal of CoQ10 supplementation resulted in a measurable decline in myocardial function within 1 month and a regression to pretreatment measurements within three to six months (Langsjoen 1994a, Langsjoen 1994b).

In 1994, Baggio published the largest open trial in heart failure, which included 2664 patients treated with up to 150 mg of CoQ10 per day. At the end of three-months, improvements were seen in vertigo (73.1%), subjective arrhythmia (63.4%), insomnia (62.8%), cyanosis (78.1%), edema (78.6%), pulmonary rales (77.8%), hepatomegaly (49.3%), jugular reflux (71. 8%), dyspnea (52. 7%), palpitations (75.4%), sweating (79.8%), and nocturia (53.6%). Over half (54%) of patients had improvement of at least three symptoms. Furthermore, 89.7% entered as NYHA class II moved up to a NYHA class I classification and 28.8% of patients entered as NYHA class III classification moved up to a class II classification (Baggio 1994).

The elderly population is of particular interest as using antihypertensive agents can be problematic because of the increased incidence of postural hypotension with resulting risk of falls and associated morbidity. Two large clinical trials in 1991 and 1997 respectively confirmed that in adults over the age of 60 with isolated systolic hypertension (systolic blood pressure >140, diastolic blood pressure <90), reducing systolic blood pressure by 20 mm Hg reduces the incidence of stroke, heart failure and mortality (SHEP Cooperative Research Group 1991, Rosenfeld 1997). Clinical trials of CoQ10 in hypertension, as well as trials of CoQ10 in cardiovascular pathologies, are summarized in Table 2.

Clinical implications The use of CoQ10 in patients with heart disease may not only be useful but imperative in achieving clinically relevant improvements in heart disease patients. While more research in this area is needed with larger “n” numbers in order to statistically better quantify its merits, much research thus far points to positive outcomes in its utilization. However, its low side effect profile and non-toxic nature makes CoQ10 a viable treatment for all age groups and across a broad range of cardiovascular pathologies.

Following positive results outlined here and elsewhere, countries like Japan, Hungary, Italy, Norway and Denmark now grant licensed prescription of CoQ10 for heart failure and ischemic heart disease (Pepe 2007), a move that shows its valued acceptance and one that encourages a more prominent and wide-spread use of CoQ10.

References

Ankola DD, Viswanad B, Bhardwaj V, Ramarao P, Kumar MN. Development of potent oral nanoparticulate formulation of coenzyme Q10 for treatment of hypertension: can the simple nutritional supplements be used as first line therapeutic agents for prophylaxis/therapy? Eur J Pharm Biopharm. 2007;67(2):361-9. Epub 2007.

Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 1994;15(Suppl):S287-94.

Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J. 2001;94(11):1112-7.

Chavey WE 2nd, Blaum CS, Bleske BE, Harrison RV, Kesterson S, Nicklas JM. Guideline for the management of heart failure caused by systolic dysfunction: Part I. Guideline development, etiology and diagnosis. Am Fam Physician. 2001;64(5):769-74.

Crane, FL, Hatefi Y, Lester RI, Widmer C. Isolation of a quinone from beef heart mitochondria. 1957. Biochim Biophys Acta. 1989;1000:362-3.

Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001;20(6):591-8.

Dunn SP, Bleske B, Dorsch M, Macaulay T, Van Tassell B, Vardeny O. Nutrition and heart failure: impact of drug therapies and management strategies. Nutr Clin Pract. 2009;24(1):60- 75.

Folkers K, Vadhanavikit S, Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci 1985;82:901–904.

Graham D, Huynh NN, Hamilton CA, Beattie E, Smith RA, Cochemé HM, Murphy MP, Dominiczak AF. Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy. Hypertension. 2009;54(2):322-8. Epub 2009.

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L- Carnitine

Heidi Fritz MA, ND

Introduction

L-carnitine is a trimethylated amino acid- derivative whose most well described biological function is as a cofactor of fatty acid metabolism (Alt Med Rev 2005). L-carnitine is a key component of the intracellular shuttle system that transports free fatty acids from the cytosol and across the mitochondrial membrane where they undergo beta oxidation and transformation to ATP (Karlic 2004). Long chain fatty acids represent up to 80% of the body’s energy sources during most physiological states with the exception of high intensity exercise (Karlic 2004) and are the preferred substrate in cardiac muscle (Carvajal 2003). L-carnitine also impacts other cellular energy- producing pathways (Mate 2010). Optimization of mitochondrial metabolism through supplementation with L-carnitine, which is known to concentrate in cardiac and skeletal muscle (Flanagan 2010), could be an effective intervention for a variety of conditions characterized by fatigue, pain, and impaired muscle function. This paper focuses on the evidence base for L-carnitine in cardiovascular medicine.

Physiology

L-carnitine is considered to be conditionally essential, meaning that although there are rare genetic conditions causing primary deficiency, and secondary deficiency resulting commonly from hemodialysis in patients with kidney disease, most healthy individuals can synthesize L-carnitine from dietary lysine and methionine and cofactors vitamin C, iron, pyroxidine, and niacin (Flanagan 2010, Mate 2010). Despite this, alterations of L-carnitine metabolism are common in cardiovascular disease, most likely due to a combination of increased utilization and the inability of myocardiocytes to synthesize carnitine endogenously.

Cardiac ischemia is well recognized in the literature to be accompanied by a rapid depletion in myocardial carnitine content and a concurrent rise in intracellular long chain free fatty acids (Gurlek 2000, Regitz 1990A, Regitz 1990B, Tarantini 2006). In patients with heart failure, serum carnitine has been correlated with impaired left ventricular systolic function as measured by echocardiography (El-Aroussy 2000). During ischemia L-carnitine is thought to offset rising concentrations of free fatty acids by facilitating mitochondrial uptake and utilization, thereby preventing the damaging effects of elevated free fatty acids: membrane damage with consequent cell swelling and microvascular compression, arrhythmias, and metabolic inefficiency with consequent deterioration of myocardial function (Tarantini 2006).

In addition to its facilitating fatty acid transport into the mitochondria, L-carnitine performs a second key metabolic function: the removal from the mitochondria of short and medium chain fatty acids (acetyl groups) formed as products of beta oxidation and bound to CoA as acetyl-CoA (Mate 2010). Mitochondrial accumulation of this byproduct is toxic, inhibiting pyruvate dehydrogenase activity and glucose oxidation. On the other hand, the removal of acetyl groups and consequent increase in free CoA stimulates energy production through the Kreb’s cycle (Mate 2010). In this way, L-carnitine can regulate both fatty acid and glucose metabolism in ischemic cardiac tissue. See Figure 1. Importantly, since myocardium is unable to synthesize carnitine itself, exogenous administration may be necessary to restore optimal levels and metabolic function.

Human Evidence

Oral and intravenous L-carnitine has been shown to be benefi cial for a number of cardiovascular conditions including angina (Bartels 1996, Cacciatore 1991), acute myocardial infarction (Gurlek 2000), chronic heart failure (Rizos 2000), and peripheral vascular disease (Brevetti 1999); because it is more accessible, this summary focuses on oral L-carnitine in particular. e typical dosage is 2g per day in divided doses (Gurlek 2000, Singh 1996); some studies have used up to 6g per day (Iliceto 1995). No adverse events beyond mild gastrointestinal upset, which was rare, were reported (Kumar 2007). It should be noted that most of the studies cited here included patients also receiving standard medications for their conditions, and that L-carnitine was studied as an “add on” therapy; space constraints limit the detail in which this can be described for each study.

Angina ere are at least eight controlled human trials of oral L-carnitine for the treatment of angina. Of these, all found benefi t (Bartels 1995, Bartels 1996, Cacciatore 1991, Cherchi 1985, Cherchi 1990, Iyer 2000, Kamikawa 1984, Lagioia 1992, McMackin 2007). L carnitine has been shown to:

• Improve cardiac function (eg. cardiac output, maximal heart rate) during exercise and improve overall exercise performance (eg. exercise time, exercise workload) despite having no eff ect on myocardial oxygen requirements (Bartels 1996, Bartels 1995, Cacciatore 1991, Cherchi 1985, Iyer 2000, Kamikawa 1984, Lagioia 1992);

• Reduce myocardial ischemia upon exercise testing, measured as the time to ST-segment depression or the degree of ST-depression on ECG (Bartels 1996, Bartels 1995, Cacciatore 1991, Cherchi 1985, Cherchi 1990, Kamikawa 1984, Lagioia 1992);

• Reverse angina, with a number of patients becoming angina- free during treatment (up to 22.7% of patients compared to 9.1% in the placebo group according to Cherchi 1985, 2 out of 12 patients according to Kamikawa 1984); • Decrease frequency of angina attacks by up to 70% and nitroglycerin consumption by 57% according to Bartels 1996, comparable to treatment with diltiazem;

• One additional study in patients without angina but with established coronary artery disease showed L-carnitine to increase brachial artery diameter by 2.3%, consistent with reduced arterial tone (McMackin 2007).

L-carnitine exerts these eff ects without reducing myocardial oxygen demand, as do select cardiac medications such as beta blockers. Bartels showed that: “[proprionyl-L-carnitine] prevents ischemia-induced ventricular dysfunction, not by aff ecting the myocardial oxygen supply-demand ratio but as a result of its intrinsic metabolic actions, increasing pyruvate dehydrogenase activity and fl ux through the citric acid cycle” (1994).

Acute Myocardial Infarction

Eight controlled trials have examined the eff ect of L-carnitine in the treatment of acute myocardial infarction (AMI), often with intravenous administration for an initial period, followed by long term oral administration. ese are summarized in Table 1. When added to standard therapies, L-carnitine has been found to:

• Improve myocardial pumping ability: increasing left ventricular ejection fraction (LVEF) (Gurlek 2000), and end- diastolic and end- systolic volumes (Iliceto 1995)

• Reduce myocardial damage: reduced infarct size when administered acutely (Singh 1996), and reduced deleterious left ventricular remodeling and dilation when administered acutely and long term (Iliceto 1995)

• Decrease angina following MI by up to half that experienced by patients receiving placebo (Davini 1992, Singh 1996)

• Decrease incidence of arrhythmias following MI (Mondillo 1995, Singh 1996)

• Reduce number of second cardiac events to 15.6%, compared to 26% in placebo (Singh 1996)

• Reduce overall mortality, with 1.2% rate reported in LC group compared to 12.5% in the placebo group according to Davini 1992. Reduced mortality also demonstrated by De Pasquale (1995).

Two large randomized controlled trials have been conducted by Italian researchers. The CEDIM1 (Carnitine Ecocardiografia Digitalizzata Infarto Miocardico) and CEDIM2 trials investigated the use of intravenous L-carnitine 9g/d for the first five days after AMI, followed by 4 to 6 g/d orally for 6 to 12 months in 472 and 2230 patients respectively (Iliceto 1995, Tarantini 2006). Although the studies differed in their long term (6-12 months) findings, both demonstrate that L-carnitine can reduce early mortality post AMI. CEDIM2 found significantly reduced early mortality, risk of death at 5 days HR 0.61 (95% CI 0.37-0.98), and upon reanalysis, it was found that much of the apparent benefit seen in CEDIM1 was also due to lower early mortality (Tarantini 2006).

Of the eight studies, seven found significant positive effects (Davini 1992, De Pasquale 1995, Gurlek 2000, Iliceto 1995, Mondillo 1995, Singh 1996, Tarantini 2006). Iyer found no effect on cardiac function in a smaller trial of 60 patients using L-carnitine 6g/d intravenously for the first 7 days, then 3g/d orally for 3 months, and it has been suggested that this may be due to the smaller trial size compared to CEDIM 1 and 2, or the lower dosage used (1999).

Heart Failure

Nine controlled trials have investigated L-carnitine for patients with chronic/ congestive heart failure (CHF) (Anand 1998, Caponetto 1994, Ghidini 1988, Kumar 2007, Loster 1999, Mancini 1992, No authors 1999, Pucciarelli 1992, Rizos 2000). L-carnitine has been shown to:

• Improve exercise performance (maximum exercise time) (Caponetto 1994, Kumar 2007, Loster 1999, Mancini 1992, No authors 1999, Pucciarelli 1992, Rizos 2000)

• Improve cardiac function during exercise (eg. peak exercise heart rate, ejection fraction) (Anand 1998, Mancini 1992, No authors 1999)

• Increase cardiac pumping ability (eg. cardiac output, stroke volume index, left ventricular ejection fraction, pulmonary blood pressure) (Caponetto 1994, Pucciarelli 1992, Rizos 2000)

• Decrease left ventricular size (Anand 1998)

• Decrease signs and symptoms associated with CHF, including dyspnea, palpitations, fatigue, edema, and improved diuresis (Ghidini 1988, Kumar 2007)

• Reduce long term mortality: in one study 3-year mortality was 3% for patients receiving L-carnitine, compared to 18% for those on placebo (p<0.04) (Rizos 2000).

Interestingly, Loster found that the beneficial effects of L-carnitine continued to persist for up to 60 days after cessation of treatment (1999).

Peripheral Vascular Disease Nine controlled trials have investigated L-carnitine, mostly as proprionyl-L-carnitine (PLC), for the treatment of peripheral vascular diseases secondary to smoking or diabetes (Barker 2001, Brevetti 1999, Brevetti 1997, Brevetti 1995, Brevetti 1988, Dal Lago 1999, Greco 1992, Hiatt 2001, Santo 2006). PLC appears to benefit predominantly those patients with moderate to severe disease, with limited effect in mild disease (Brevetti 1999, 1997, Silvestro 2006). PLC has been shown to:

• Increase walking time and/ or distance, by up to 98% in those with moderate to severe disease (Brevetti 1999, Brevetti 1995, Brevetti 1988, Dal Lago 1999, Greco 1992, Hiatt 2001)

• Increase intermittent claudication distance (the distance walked until onset of claudication) (Brevetti 1999, Santo 2006)

• Improve ankle-brachial index (Greco 1992, Santo 2006)

• Improve quality of life (Brevetti 1997)

Intravenous PLC infused 3 times weekly has also been shown to augment the effects of a physical training program in patients with moderate to severe intermittent claudication (Andreozzi 2008). Biopsy of ischemic muscle has shown that supplementation with PLC increases muscle total carnitine content after 15 days (Brevetti 1988); and uncontrolled trials have shown an ability of PLC to attenuate cold induced decreases in blood flow in patients with vasospastic disease such as Raynaud’s (Gasser 1997) and reduce exercise induced increases in serum adhesion molecules, suggesting vasoprotective effects (Signorelli 2001).

Conclusion

L-carnitine is a necessary cofactor for mitochondrial function, stimulating oxidative metabolism of glucose and fatty acids particularly under conditions of ischemia. L-carnitine protects against ischemiainduced myocardial dysfunction and has been demonstrated to improve cardiac function and exercise performance in patients with angina, myocardial infarction, and heart failure. L-carnitine can decrease frequency of angina attacks; reduce deleterious cardiac remodeling and arrhythmias, and improve survival after MI; and decrease symptoms of CHF while increasing long term survival. L-carnitine also benefits peripheral vascular disease. L-carnitine has been administered alongside standard cardioactive medications in many of the trials described above without report of any serious adverse events, and can be safely considered for comanagement of the cardiac patient.

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