The Journal of American Geriatrics recently reported that once weekly tai chi classes significantly reduced the number of falls in a group of elderly individuals. This is similar to other reports published previously that showed twice-weekly tai chi classes were effective at reducing fall rate in elderly persons.
Posted
10/22/2007
Medicatoin-Assisted Manipulation: A literature Review of 49 published articles
Scott Haldeman, DC, MD, PhD published in the Spine Journal in 2002 a literature review of medication-assisted manipulation in 49 published articles.
This procedure has been well documented in the medical literature for over 70 years.
The typical manipulation under anesthesia (MUA) procedure involves placing the patient in a twilight anesthesia by a board-certified anesthesiologist while the chiropractor, with the aid of a skilled trained assistant, provides specific mobilization and manipulation techniques to the affected joints and spinal regions.
Recent advances in highly titratable and reversible intravenous anesthesia allows this to be an out patient procedure using non-paralytic anesthesia or sedation while the patient continues to breathe on their own.
The rationale for the use of MUA is that anesthesia and analgesia help to eliminate or reduce pain and muscle spasm that hinder the effective use of traditional manipulation allowing the practitioner to break up joint adhesions and reduce segmental dysfunction to a greater extent than if anesthesia had not been employed.
The earliest MUA study was published in 1930 by The Lancet and demonstrated an overall 75 percent of chronic lumbar pain patients improved.
In an initial study by Siehl and Bradford published in 1952, 33 percent of the patients reported they were symptom free post procedure.
In 1964, Chrisman’s study showed 83 percent of the subjects reported good or excellent results after a 3-year follow-up.
In Morey’s 1973 study, he reported excellent or good results in 85 percent of the cases.
In a study published in 1986 by Krumhansel and Nowacek outcomes were reported as 25 percent ‘cured’, 50 percent ‘much improved’, and 20 percent ‘better'.
In a 1990 article by Mennell, 30 percent with symptoms cured, 35 percent with marked improvement, 29 percent with moderate improvement.
In a recent 2004 case series by West et al VAS scores improved 4.6 points for cervical pain and 4.31 points for lumbar pain with a decrease in time off work and less use of prescription pain medication were reported.
Medication-assisted manipulation appears to offer patients increased improvement in low back pain and disability when compared to usual in office chiropractic care.
A 2005 study by Kohlbeck et published in SPINE journal showed that the relative odds of experiencing a 10-point improvement in pain and disability favored the medication-assisted manipulation group at 3 months and one year follow up.
This randomized controlled trial was conducted at The University of Queensland's Townsville Hospital, School of Public Health and Tropical Medicine by the National Unit for Multidisciplinary Studies of Spinal Pain and published in SPINE journal. (SPINE 2003;28:1490-1503)
The highest proportion of early asymptomatic recovery was found in the chiropractic manipulation group (27.3%), followed by acupuncture (9.4%) and medication (5%). Chiropractic manipulation resulted in greater short term improvement than medication or acupuncture. However, the data do not strongly support only the use of manipulation. While all three interventions showed some positive response, acupuncture was shown to be more efficacious for neck pain on the VAS. This study was exclusively concerned with chronic spinal pain and therefore no results can be extrapolated regarding the role of medication in treating acute spinal pain.
Posted
9/18/2007
Whole Grain, Bran, and Germ Intake and Risk of Type 2 Diabetes
This study observed a substantial inverse association between whole grain intake and risk of type 2 diabetes. Based on a meta-analysis of six cohort studies, a two-servings-per-day increment in whole grain intake was associated with a 21% decrease in risk of type 2 diabetes. Findings from prospective cohort studies consistently indicate that higher consumption of whole grains can contribute to the prevention of type 2 diabetes.
Posted
9/18/2007
PSA Value Is a Poor Predictor of Prostate Cancer Outcome
This study published in April 4 issue of the Journal of the National Cancer Institute (J Natl Cancer Inst. 2007;99:526-532) shows that prostate-specific antigen (PSA) performs poorly in distinguishing those who will develop prostate cancer from those at low or no risk. Although initial PSA values and the rate of change were associated with later development of lethal prostate cancer, they were not accurate enough to predict lethal cancer. The authors explained, "If we simply use a PSA doubling time of 5 years as a guide, in this group of patients approximately 36% of deadly tumors would be missed and 40% of men with indolent tumors would be treated unnecessarily." The authors call for better decision-making tools for active monitoring of patients with early disease.
Posted
9/18/2007
Meta-Analysis Suggests Folic Acid Reduces Risk for Initial Stroke
The findings are published in the June 2 issue of the Lancet. (Lancet. 2007;369:1876-1882, 1841-1842.) The literature was searched to April 2007. The meta-analysis included 8 randomized controlled trials, consisting of 16,841 patients. A meta-analysis of the 8 randomized controlled trials reports that folic-acid supplementation reduced first stroke risk by 18%. This study was not able to determine what dosage of folic acid is best or whether it should be given alone or in combination with 1 of the B vitamins.
Posted
9/18/2007
Blood-Pressure Changes With Acupuncture Comparable to ACE-Inhibitor Monotherapy
(Flachskampf FA, Gallasch J, Gefeller O, et al. Randomized trial of acupuncture to lower blood pressure. Circulation 2007; DOI: 10.1161/CIRCULATIONAHA.106.661140.) This RCT enrolled 160 outpatients with mild to moderate hypertension who were randomized to six weeks of acupuncture or to a sham procedure. At the end of the six weeks and 22 sessions, 24-hour ambulatory systolic and diastolic blood pressures were significantly reduced from baseline in the acupuncture-treated patients (5.4 mm Hg and 3.0 mm Hg, respectively). No meaningful changes were seen in the sham group.
Posted
9/18/2007
Coenzyme Q10 for Relief of Muscle Ache in Patients Treated with Statins
In a small study published in Annals of Internal Medicine, coenzyme Q10 supplements conferred a considerable benefit for muscle pain relief in patients taking statins. (Kodama S et al., Arch Intern Med 2007 May 28; 167:999-1008. Coenzyme Q10 for Relief of Muscle Ache in Patients Treated with Statins.) Muscle pain intensity decreased by 40% in the coenzyme Q10 group compared with no change in muscle pain intensity in the vitamin E control group (P<0.001).
Posted
9/18/2007
Antioxidant Vitamins a Bust at CV Protection
Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta-carotene in the secondary prevention of cardiovascular events in women: Results from the Women's Antioxidant Cardiovascular Study. Arch Intern Med 2007;167:1610-1618. The Women's Antioxidant Cardiovascular Study (WACS)published findings in the August 13/27, 2007 issue of the Archives of Internal Medicine. The aim of this trial was to test the effect of 3 antioxidant agents, vitamin C, vitamin E, and beta-carotene, on the prevention of cardiovascular disease among women at high risk. The WACS found that there were no overall effects of vitamin C, vitamin E, or beta-carotene alone or in combination on cardiovascular events among women at high risk for cardiovascular disease.
Posted
9/18/2007
Acupuncture more effective than usual care for osteoarthritis
This meta-analysis (RCTs) was published in Annals of Internal Medicine (Manheimer E, Linde K, Lao L, Bouter LM, Berman BM. Meta-analysis: acupuncture for osteoarthritis of the knee. Ann Intern Med 2007;146:868-877) Acupuncture produced a demonstrable effect on osteoarthritis pain as well as functional measurements. Whether this is an intrinsic effect of acupuncture or due to placebo, is not well defined. Nonetheless, patients reported feeling better in both the short term and the long term as compared with usual care or patients on a waiting list.
Posted
9/18/2007
High Sugar Intake May Increase Risk for Pancreatic Cancer
Published in November issue of Am J Clin Nutr. 2006;84:1171-1176. This prospective, population-based cohort study examines the relationship between sugar intake and incidence of pancreatic cancer. Statistically, pancreatic cancer survival rate is less than 5%. Abnormal glucose metabolism and hyperinsulinemia may be involved in the development of pancreatic cancer and DM is associated with almost 2 times increased risk for pancreatic cancer. It is also thought that consumption of added sugar and soft drinks may increase pancreatic cancer risk. From the study: * Those consuming a diet with a high sugar intake had a lower level of education and were smokers. * High intake of sugar and soft drinks is linked with increased risk for pancreatic cancer during 7 years of follow-up.
Posted
9/18/2007
Firefighters and Deaths from Heart Disease
Published in March 2007 issue of CARDIOLOGY: About 45% of deaths among on-duty firefighters are due to heart disease. 32% of the deaths occurred during fire suppression activities, even though fire suppression accounts for about 1-5% of firefighters' on-duty time. Death from heart disease is markedly elevated during emergency duties. It will be interesting to see if upcoming studies will investigate the effects of stess management in this high stress profession.
Posted
8/31/2007
Omega-6 Fatty Acid Consumption Related to Depression and Inflammation
Published in April's issue of Psychosomatic Medicine: Older adults who ate diets high in omega-6 fatty acids and low in omega-3 fatty acids had higher levels of proinflammatory cytokines than persons who ate a more balanced diet.
Particularly interesting was the finding that people with higher levels of depressive symptoms were more susceptible to increased inflammatory changes as their omega-6 to omega-3 ratio increased. And in persons with lower levels of depressive symptoms, diet didn't seem to play as big a role in inflammatory changes.
Depression and stress have long been known to cause an increase in proinflammatory cytokine production. Omega-3 fatty acids are found in cold water fish, flax seed oil, nuts and fresh fruits and vegetables. Omega-6 fatty acids are found in margarine, lard, fried foods, as well as fast foods.
This small study shows the importance of diet in physical and mental health.
A study published in the March issue of "Diabetes Care" reported that certain kinds of exposure to pesticides during the first trimester of pregnancy increased the risk of gestational diabetes.
Women who mixed or applied pesticides or repaired pesticide equipment during the first trimester of their pregnancy developed gestational diabetes more than twice the expected rate.
Women with simply residential or indirect exposure to pesticides during their first trimester had no increased risk of developing gestational diabetes.
We are beginning to learn more about the longterm metabolic effects of pesticides. It will be interesting to see how our agricultural practices change in response to some of these new studies.
Posted
3/20/2007
Integrative therapies at a tertiary care health center
A survey of clinicians from multiple departments at the University of North Carolina found a strong interest in offering several specific therapies: therapeutic exercise (77%), expert consultation about herbs and dietary supplements (69%), and massage (66%); there was even stronger interest in offering comprehensive treatment programs such as multidisciplinary pain management (84%), comprehensive nutritional assessment and advice (84%), obesity/healthy lifestyle promotion (80%), fit for life (exercise and lifestyle program, 76%), diabetes healthy lifestyle promotion (73%); and comprehensive psychological services for stress management, including hypnosis and biofeedback (73%).
Patients between the ages of 18 years and 70 years (n=120) undergoing ambulatory knee surgery were randomized to receive either auricular acupuncture using traditional sites recommended by traditional Chinese medicine or sham acupuncture using other sites on the auricle.The median ibuprofen requirement was 600 mg in the control group and 200 mg in the acupuncture group. This small but positive outcome suggested the benefit of further studies of acupuncture in post-operative pain
Usichenko TI, Kuchling S, Witstruck T, et al. Auricular acupuncture for pain relief after ambulatory knee surgery: a randomized trial. CMAJ 2007;176:179-183. Links: - Usichenko TI, Kuchling S, Witstruck T, et al. Auricular acupuncture for pain relief after ambulatory
Posted
3/8/2007
Yoga and mood disorders
Preliminary findings support the potential of yoga as treatment of depressed patients who are taking anti-depressant medications but are not in complete.remission. This article presented further data on yoga as an intervention, focusing on individual differences in psychological, emotional and biological processes affecting treatment outcome. Twenty-seven women and 10 men were enrolled in the study, of whom 17 completed the intervention and pre- and post-intervention assessment data. The intervention consisted of 20 classes led by senior Iyengar yoga teachers, in three courses of 20 yoga classes each. All participants were diagnosed with unipolar major depression in partial remission. Psychological and biological characteristics were assessed pre- and post-intervention, and participants rated their mood states before and after each class. Significant reductions were shown for depression, anger, anxiety, neurotic symptoms and low frequency heart rate variability in the 17 completers. Eleven out of these completers achieved remission levels post-intervention. Participants who remitted differed from the non-remitters at intake on several traits and on physiological measures indicative of a greater capacity for emotional regulation. Moods improved from before to after the yoga classes. Yoga appears to be a promising intervention for depression; it is cost-effective and easy to implement. It produces many beneficial emotional, psychological and biological effects, as supported by observations in this study. The physiological methods are especially useful as they provide objective markers of the processes and effectiveness of treatment. These observations may help guide further clinical application of yoga in depression and other mental health disorders, and future research on the processes and mechanisms. In conclusion, yoga appears to be a promising intervention for depression. It is cost-effective and easy to implement. Most importantly, yoga produces many beneficial emotional, psychological, behavioral and biological effects, as supported by observations in this study. The physiological methods are especially useful as they provide objective markers of the processes and effectiveness of the intervention. The methods and observations in this report may help guide further clinical research on the application of yoga in depression, with appropriate placebo control and comparison conditions, and in other mental health disorders, and in future research on the processes and mechanisms involved. Links: -Yoga as a Complementary Treatment of Depression: Effects of Traits and Moods on Treatment Outcome, S
Posted
8/31/2007
Does Crying Help?
In an interesting study, Japanese researchers found that crying may relieve pain and inflammation. They studied patients with Rheumatoid Arthritis by watching them while they were visually exposed to emotional stimuli. They also looked at blood levels of stress hormones and immune globulins. Of note, they found that those patients who were most easily moved to tears had less pain, swelling and need for pain medications over the next year. So, maybe Crying Does Help! Links: - Clin Exp Rheumatol. 2003;21;611-616
Posted
2/23/2007
Noni Juice
Recently there has been a lot of press about Noni Juice and companies selling it have claimed that it can treat everything from depression to headaches to high cholesterol.
There is very little clinical evidence that Noni Juice can treat disease. However, there is a longstanding history of its use as a health tonic in the Polynesian culture and many times these historically used remedies have been shown to have health benefits. We just don't have enough information at this time to back up the claims that marketers are making. Noni Juice doesn't taste very good, but does have many vitamins and antioxidants as is common with many other fruit juices.
Noni Juice is considered safe to drink with one word of caution. It contains substantial amounts of potassium; so, persons with chronic renal failure or insufficiency, those on diuretics, ACE Inhibitors or ARB's should consult their physician prior to taking Noni Juice.
Posted
2/16/2007
Acupuncture and back pain.
A new study reveals that acupuncture is is as effective as a range of usual care provided by physiciansover a 1-2 year period. No surprise to me as this is the most common reason folks come in for acupuncture. Still, it is good to see some supporting science that will helpfully motivate insurers to cover it more wide.y
Reference: Thomas KJ, MacPherson H, Thorpe L, et al. Randomised controlled trial of a short course of traditional acupuncture compared with usual care for persistent non-specific low back pain. BMJ 2006;333:623.
Posted
1/17/2007
Addiction and Alcoholism
Integrative Drug Addiction Treatment for the Twenty First Century Victor Sierpina, MD Lodie Massey, BS, MA, PA
“Never give up.” In the darkest days of World War II, Winston Churchill advised the British, “Never, never, never, never, never give up!” The challenges of addiction and substance abuse require perseverance of similar dimensions. Recovery and sobriety are lifelong tasks for those who suffer from addictions and it is essential that those of us providing care for patients with addiction understand its chronicity and high recurrence rates.
I once admitted a patient for rehabilitation from poly-substance abuse. While pleased that he came to me stating he was ready to change his long-term problem by a commitment to detoxification and rehabilitation, I was taken aback when during his history I found that he had previously been in 13 or 14 treatment programs, only to slip back into his old behaviors. With limited expectation that this admission would be anything more than another transient attempt to solve his problem, I admitted him to our hospital’s drug and alcohol treatment program.
To my pleasure and astonishment, this 15th trip to rehab seemed to be the one that “worked.” More than three years later, he continued to be sober, drug-free, and vigilant against relapse with regular attendance at Alcoholics Anonymous and Narcotics Anonymous groups. His wife and children became the center of his life and support system rather than substances. He taught me a BIG lesson…. Never give up. While work with the addictive person can often be discouraging, the rewards of sustained effort, perseverance, and patience are enormous. Having a deep trust that at some level, those with such problems have the capacity to heal and be well is necessary to the task of being a helping professional.
In the year 2007, most health care professionals have learned that drug addiction (of course, alcohol is included as a drug) is a complex, chronic, progressive disease. Hopefully, they have also learned that it can be treated, just as other complex, chronic, progressive diseases, such as hypertension and diabetes, are treatable.
The goal of drug addiction treatment is not just abstinence, but also improving the patient’s ability to function in the family, workplace and society, and minimizing medical and social complications of drug abuse and addiction. Untreated substance abuse and addiction hurts families and communities, resulting in increased violence and property crimes, prison expenses, court and criminal costs, emergency room visits, healthcare utilization, child/spousal abuse and neglect, foster care and welfare costs, reduced productivity and unemployment.
In 2004, approximately 22.5 million Americans age 12 and older needed treatment for substance (alcohol or illicit drug) abuse and addiction. Despite extensive data that documents drug addiction treatment is as effective as are treatments for most other similar chronic medical conditions, only 3.8 million of the affected individuals received it. Why don’t more people receive treatment?
Addiction has so many dimensions and disruptions to multiple aspects of a person’s life that treatment is never simple. This fact, coupled with the opinion of many (including some medical professionals) that treatment does not work, despite extensive data to document otherwise, results in many people not receiving treatment that might lead to recovery. Many people equate addiction with simply using drugs, and expect that addiction should be cured quickly, and if it is not, treatment is a failure. In reality, recovery usually requires sustained and repeated treatment episodes.
There is not a “one size fits all” treatment for addiction, just as not all people with diabetes should be given the same dosage of insulin. Over 30 years of scientific research and clinical practice have yielded a variety of approaches to effective drug addiction treatment.
Treatment may, or may not, begin with detoxification. However, medically assisted withdrawal is not in itself “treatment” only a first step in the treatment process. Research shows that patients who undergo only medically assisted withdrawal, without receiving further treatment show drug abuse patterns similar to those who received no treatment at all.
Long term drug use results in significant changes in brain function that persists long after cessation of use. Therefore, a period of intensive treatment is required, and may take the form of inpatient/residential or outpatient treatment. Studies show that participation for less that 90 days in this level of treatment has limited or no effectiveness, therefore three months is the minimum length recommended. During this time, a treatment plan is developed for the patient, that will include education, behavioral therapy, and participation in a support group (usually a 12 step group). Behavioral treatment may include: cognitive behavioral therapy, multidimensional family therapy, and motivational interviewing. During this time it is important for the patient to maintain good nutrition, establish a support system of drug free people, and receive necessary treatment for medical problems. High dose B vitamins, zinc, and magnesium supplementation are particularly helpful. Just a few of the medical consequences associated with drug use are cardiovascular disease, stroke, HIV/AIDS, and hepatitis.
Initially, treatment programs discouraged patients from using drugs of any form. However, most now recognize that some patient may benefit from prescribed medications. If the patient has a co-occurring mental illness, medications such as antidepressants, mood stabilizers, or neuroleptics may be critical for treatment success.
Methadone and buprenorphine are effective medications for the treatment of opiate addiction. Acting on the same targets in the brain as heroin and morphine, these medications act to block the abused drug’s effects, suppress withdrawal symptoms, and relieve cravings for the drug of choice. This enables the patient to be more receptive to behavioral treatments. Buproprion is often useful in tobacco withdrawal and a new produce varenicline is targeted to affect nicotine receptors in the CNS . Tricyclics, SSRI’s, MAOI’s, and amantadine have all been used in cocaine treatment for cravings and relapse prevention.
After the intensive phase of treatment, it is important for the recovering patient to receive continuing care, which may take the form of individual or group therapy, support group participation, and or/ prescribed medications. Indeed, just as the addictive process is polyfactorial, an integrative treatment approach is fundamental and must recognize the multiple levels of mind, body, spirit, social, emotional, vocational, legal issues involved in both the addiction and the recovery process.
In addition to medical detoxification, social and group treatments, and medications, a number of alternative therapies can be considered for the treatment of addiction. Acupuncture has been widely employed to reduce both the cravings and withdrawal syndrome from opiates, cocaine, and tobacco. Though clinical studies show mixed results, long-term benefits by groups such as Dr. Michael Smith’s Lincoln Hospital in the Bronx treatment program and the National Acupuncture Detoxification Association (NADA—http://acudetox.com) have shown sufficient benefits that judges in a number of jurisdictions have remanded repeat offenders to auricular acupuncture treatment as a step toward rehabilitation. In fact, the role of endorphins in the mechanism of acupuncture was first suspected when post-operative opium addicts in Hong Kong who had received electroacupuncture for post-surgical analgesia did not experience typical narcotic withdrawal that those who did not receive acupuncture.
A traditional Chinese herb, kudzu, has been known for centuries as an “anti-inebriation” treatment though its mechanism of action is not know. Some botanicals such as valerian and kava kava might be useful in reducing the anxiety and insomnia associated with withdrawal. They affect levels and action of GABA so may have a role in reducing alcohol cravings and in relapse prevention. Milk thistle is widely used for its hepatoprotective effect and is most useful in toxic hepatitis such as that induced by alcohol.
Relaxation and reduced physiological responses to stress are highly useful to the recovery process. Such changes can be induced by a variety of mind-body therapies such as meditation, guided imagery, yoga or tai chi, biofeedback, and hypnosis. By providing patients with experience using such techniques, daily stressors that might make them reach for a cigarette, drink, or a drug can be approached differently with higher autonomy and range of options. Spirituality is also highly useful in the treatment of addictions and is the basis for twelve-step programs such as Alcoholics Anonymous. Strong involvement in spiritually based treatment programs provided social support and a reformed view of the world that can be very useful to recovery. When I practiced in Colorado, I was medical consultant to Teen Challenge, a residential recovery program for addicts and their families. Based on a model in which participants were involved in intense Biblical and Christian training, this voluntary 9-12 month treatment program had an incredibly high rate of 70% of its graduates maintaining a drug-free lifestyle 2 years following completion. Various ethnic groups have other culturally imbedded therapies for substance abuse such as the Native American sweat lodge and talking circle.
So, remember Churchill’s’ admonition to “never give up.” By equipping yourself with a wide variety of approaches to addiction along with the persistence and faith to maintain the relationship with the patient despite the inevitable recurrences, you will be in the best role to be a healing and change agent in their lives.
Victor S. Sierpina, MD is the W.D. and Laura Nell Nicholson Family Professor of Integrative Medicine and Professor, Family Medicine at the University of Texas Medical Branch, Galveston, Texas.
Lodie Massey founded the Gulf Coast Center Recovery Programs in 1990 and was director 1990-1995. She has a BS from UTMB-Galveston and an MA from the University of Houston. She also has many years of clinical experience as a Physician’s Assistant.
Links: - http://acudetox.com
Posted
1/17/2007
Acupuncture and ulcerative colitis
This study suggests that acupuncture provides a symptomatic benefit for patients with ulcerative colitis, The authors have also studied acupuncture for Crohn's disease and found similar benefits (Digestion 2004;69:131-139).
Joos S, Wildau N, Kohnen R, et al. Acupuncture and moxibustion in the treatment of ulcerative colitis: a randomized controlled study. Scand J Gastroenterol 2006;41:1056-1063.
Posted
1/17/2007
Genomic Wellness
Genomic Wellness
Victor S. Sierpina, MD WD and Laura Nell Nicholson Family Professor of Integrative Medicine UTMB
Wellness promotion emphasizes those activities, attitudes, and behaviors that promote optimal well being. Wellness is more than a state of “not being sick” but rather utilizes a model focused on function and thriving rather than one predominantly occupied with disease treatment or even disease prevention. While it is true that optimal human function can best occur in the absence of disease or at least maximal possible control of the morbidities associated with illness, wellness promotion emphasizes what we actually do with good health to best optimize our personal goals and potentialities.
In the personalized health care and wellness promotion of the future, genetics and genomics will play and increasingly important role. Health futurist Leland Kaiser’s essay, “Designer Health Care for a Designer Nation” predicted increasingly individualized assessments and therapeutic plans tailored to individuals and their personal preferences and physiology.1
While long part of traditional healing systems such as Traditional Chinese Medicine, Ayurvedic, and various indigenous healing systems, individualized treatment planning has generally not been a part of conventional medical culture. Randomized controlled trials, highly useful for determining the benefit of treatments, tend to blur distinctions about individualized responses. This results in a “one size fits all” prescription for standard treatments, mainly based on pharmaceutical interventions. As a result, we rarely know what treatment will really work best for what individual patient. We end up with trial and error. If this drug doesn’t work or gives an adverse reaction, we’ll try another one, etc.
In recent years, the Human Genome project and other genetic research has revealed the significance of variations in individual physiology in responding to drugs and other therapeutic interventions. Single nucleotide polymorphisms (SNP’s) can be significant in determining the way drugs are metabolized, in how individuals respond to nutritional interventions, stress, environmental toxins, and other epigenetic influences. These SNP’s are not evident at the level of the phenotype but must be assessed by molecular methods.
While much has been made of the importance of genes in determining our health and some major expectations have been created about engineering genes to prevent and treat disease, the influence of wellness promoting behaviors, diet, exercise, stress management, social and spiritual support are estimated to produce 70-80% of the modifiable health benefits we can obtain beyond what our parents bequeathed to us in our DNA. Indeed such wellness promoting activities are now known to be effective by mediating activation and regulation of gene expression and subsequent protein and metabolic modification.
Here is the opportunity we have for the integrative medicine of the future. Wellness promotion and optimization of human performance can make use of highly specific information based on a person’s genetic profile, family history, and biochemical/biological individuality based on SNP’s and other polymorphisms. Using this information, we can be in an enormously powerful position to predict response to drugs, to exercise, to nutritional prescriptions (nutrigenomics), to stress (proteomics of stress is a newly evolving field), and to reduce disease risk based on these individualized profiles. This is both a new and old domain in wellness promotion. As the ancient Chinese Golden Emperor was quoted to say, “The superior physician treats the disease before it occurs.”
Let me give an example of how a “wellness consult” would work, in the near future.
A 42 year old female executive of Hispanic origin presents for a comprehensive genomic-based evaluation. She feels well with no specific complaints and is up to date on usual health maintenance, screenings, and immunizations for her age. In addition to a history that closely details her personal and family medical history, additional attention is paid to allergies, adverse drug reactions, and food intolerances. A complete physical would be complemented by advanced imaging techniques for early detection of illness and laboratory testing would include not only standard hematological, metabolic, and organ function evaluations but also genomic analysis and profiling. Such testing would include identifying specific familial risks for cancer, heart disease, diabetes, and other common diseases but also stratifying risk according to biological polymorphisms that may raise or lower such generalized risk. Prior to prescribing a dietary or drug therapy, known genes affecting or effecting the utilization of certain drugs and foods will be identified. This information will be used to define a specific therapeutic plan.
In this case, Ms. Romero was noted to have several family risks for both diabetes and cardiovascular disease. However, a specific set of alleles in her case provides reduction of such risks. Further testing shows that she is a slow metabolizer of several drugs and botanicals and that these should be either avoided if used, or dosed at lower than usual levels. Specific dietary interventions and supplements are planned based on polymorphisms showing that she needs higher levels of B vitamins such as B6 and folic acid than the general population. A nutrigenomic analysis found that that she would benefit from increasing cruciferous vegetables in her diet like broccoli and cauliflower. These would stimulate her hepatic glutathione detoxification mechanisms which are currently stressed because of she works at a chemical plant and lives in a city with high levels of air pollution. Higher doses of essential fatty acids provided as refined fish oils are also noted to be necessary because of low levels of these in her cells and because of their benefit in reducing risks from atherosclerosis, stroke, and heart disease.
An exercise program and consult with an exercise physiologist is recommended to further lowers her risk of CAD and DM. She is referred to a class providing stress management techniques, relaxation therapies and yoga. These are recommended for her due to the highly demanding executive position she holds and the impact this has on activating cortisol, catecholamines, and inflammation.
She leaves with a personalized plan for care that minimizes the impact of genetic and personal antecedents for illness, works to reduce triggers for future disease, and helps her with positive steps toward a wellness lifestyle. She is offered the option of wellness coach to help keep her on track and accountable for these changes in her new wellness lifestyle.
A fully developed wellness plan addresses all areas of human functioning and health: physical, mental, spiritual, social, and environmental. By incorporating genomic analysis, the integration of all of these inputs can be better amplified and refined. Lest we become too enamored of the possibilities of prevention or post facto genetic treatment, I would like to close with a quotation from Walter Willett, MD of Harvard University’s School of Public Health:
“Genetic and environmental factors, including diet and life-style, both contribute to cardiovascular disease, cancers, and other major causes of mortality, but various lines of evidence indicate that environmental factors are most important. Overly enthusiastic expectations regarding the benefits of genetic research for disease prevention have the potential to distort research priorities and spending for health. However, integration of new genetic information into epidemiologic studies can help clarify causal relations between both life-style and genetic factors and risks of disease. Thus, a balanced approach should provide the best data to make informed choices about the most effective means to prevent disease.” 2
A wellness consult in the future will thus make the most of high tech genomic analysis but will be fundamentally rooted in what we know has the most effect on how the genetic hand we were dealt can best be played. To achieve our highest dreams and aspirations, wellness promoting choices in diet, exercise, stress management, psychosocial and spiritual support, and a healthy environment free of air, water, and noise pollution will remain as the basics for optimizing our functions and potential as human beings.
1. Kaiser L. Designer health care for a designer nation: a new paradigm. In: Bezold C, ed. Future Care: Responding to the Demand for Change. New York, NY: Faulkner & Gray; 1996:189-218.
2. Willett WC. Balancing life-style and genomics research for disease prevention. Science. 2002;296:695-98
For Further Reading:
Jones DS, Quinn S. Textbook of Functional Medicine. Gig Harbor, WA: Institute for Functional Medicine, 2005.
Ardell, D. 14 Days to Wellness—The Easy, Effective, and Fun Way to Optimum Health. Novato Ca: New World Library, 1999
Posted
11/22/2006
Integrative Approaches to Dermatological Conditions:
Integrative Approaches to Dermatological Conditions: Beyond Topical Steroids
Victor S. Sierpina, MD W.D. and Laura Nell Nicholson Family Professor in Integrative Medicine University of Texas Medical Branch
Did you ever consider the challenges dermatologists must have faced in the era before topical steroid creams and ointments were formulated? These useful agents have become so much a part of our prescribing culture that other effective remedies are either ignored or never taught to our students and house staff.
Some of these are folkloric applications of herbal formulas, poultices, and salves that have been used across many cultures and many centuries. Aloe, calendula, and chamomile are among the best known of these botanical remedies. St. John’s Wort oil is an antiseptic as are many of the essential oils such as oil of oregano and tea tree oil which can be antiviral, antibacterial, and antifungal. Simple and inexpensive agents like petrolatum are often underutilized.
From my days as a country doctor in Colorado, I learned of many an excellent remedy from ranchers, farmers, and veterinarians that are also useful in humans. One that I still regularly prescribe is Bag Balm®, a soothing mixture of lanolin, petrolatum, an antibiotic, and other ingredients applied for giving “udder relief” to dairy cows. A hefty green tin of this available for about five dollars at all feed stores and now even in many pharmacies. It is tremendously useful in dried cracked skin in humans as well as other eczematoid conditions. The patient who taught me about this was a state trooper with severe cracking and fissures on his hands and feet. While every potent steroid cream and emollient known to modern dermatology had been tried, only when he tried Bag Balm® did his impossibly dry skin condition begin to recede. As the medical director of a Colorado ski patrol, I was surprised to find that patrollers whose hands had dried out and started fissuring on the fingers due to cold, wind, and dryness sealed them with Super Glue® until they could heal. Of course, we now use a similar product for repair of small skin lacerations. Oatmeal baths, another esteemed remedy for chronic itching remains helpful as do mother’s over the counter remedies like calamine.
Other lesser known methods applied in integrative dermatology are mind-body methods, nutritional supplements, essential fatty acids, and dietary allergy methods. An excellent example is atopic dermatitis, a chronic eczema seen from infancy on. When these children do not respond quickly or fully to topical steroids or the parents fear the effects of chronic steroid use, it is useful consider an elimination diet. Many children will respond to elimination of the most common culprits which are egg, cow’s milk, wheat, soy, and peanuts. I usually eliminate cow’s milk first and then the others in a step wise fashion as a diet without any of these is rigorous and hard to maintain. Attention to maintaining a fully balanced diet is essential with any kind of prolonged elimination diet. Skin prick testing, RAST testing, and oral food challenges are methods to determine specific allergic sensitivities. A negative skin prick test has the highest negative predictive value. However positive predictive values of both RAST and skin testing have limited specificity. Often the best solution is an elimination diet based on the most common allergens. Tree nuts, fish, and shellfish are other common food allergens in children. Of course, food allergy must be strongly considered in the differential diagnosis of urticaria. Breast fed children are less prone to atopic dermatitis as well as infection suggesting a protective effect, perhaps at the gut mucosal barrier, so breast feeding ought to be considered primary prevention, especially in families with known history of atopy, asthma, and allergic rhinitis.
Stress may also play a role in a variety of skin diseases. An interesting study done by Kabat-Zinn on psoriasis patients undergoing phototherapy found a highly significant improvement compared to controls when those undergoing light treatments listened to a relaxation, mindfulness-based stress reduction tape during their phototherapy sessions. Likewise a number of studies have supported the adjunctive benefit of reducing stress, improving the family environment, hypnosis, and biofeedback in reducing symptoms in atopic dermatitis. Stress can cause other skin diseases to flare as well. I clearly recall during my residency a patient who developed giant urticaria whenever her ex-spouse came into town and it resolved quickly when he left. Extensive food, drug, and allergy testing on her were entirely negative.
Of course, having a chronic skin disease is in itself a stress and has negative impact on self-esteem in many patients. Thus, a variety of stress management techniques, cognitive strategies and affirmations, relaxation and imagery can be useful. A study of visualization in childhood warts found significant reduction in warts on one side of the body compared to the other so there may be direct benefits to the immune system as well. Curiously, another study found cimetidine also useful for eliminating warts in children. Massage may be useful in application of skin emollients to both children and adults because of the affirming human contact since these patients often feel decreased attractiveness because of their skin condition.
As for many allergic conditions, improving environmental conditions and lowering the exposure of co-allergens such as dust mites can be useful in atopic dermatitis. At times, co-allergenic reactions occur with foods and these can best be determined by observation. A child who develops hives after having milk and fish sticks but not on having them separately is an example of a co-allergen reaction.
Evening primrose oil and fish oil are essential fatty acids involved in cellular membrane stability and also in the inflammatory pathways. Clinical trials do not support the use of these in atopic dermatitis though individual patients may respond well. Perhaps the grandmotherly recipe of cod liver oil may still have some relevance in the treatment of atopic dermatitis and other skin conditions. Vitamin C and zinc are useful to assist in wound healing and in reducing easy bruising, commonly seen in the elderly. Natural sunlight improves Vitamin D availability and can be useful in a variety of skin conditions, including psoriasis. Sea water has a natural astringent effect as well so a day at the beach in Galveston might be just what the doctor ordered for a chronic skin problem.
An integrative approach to dermatology requires an understanding of the wide variety of traditional and contemporary products available, attention to mind and body, consideration of allergic and nutritional factors, and perhaps just a bit of home wisdom.
Posted
11/22/2006
Integrative Cardiology
Integrative Cardiology
Victor S. Sierpina, MD Professor, Family Medicine W.D. and Laura Nell Nicholson Family Professor of Integrative Medicine University of Texas Medical Branch Galveston, TX
Fat is good for your heart.
Well, at least the right kind of fat….
The imbalance between healthy and unhealthy fats in the American diet is a major contributor to heart disease and chronic inflammation. One of the most fascinating developments coming out of the integrative medicine and cardiology scientific and research communities in recent years is the recognition that inflammation is a critical factor in the development and manifestations of atherosclerosis and coronary artery disease. Indeed, a recent article in the Wall Street Journal described how insurance companies are now increasing their coverage for certain dental care procedures because chronic inflammation of the gums and tooth problems contributes to both heart disease and diabetes.
One important aspect of inflammation is the role played by the arachidonic acid-derived cytokines. Our typical American diet is fueled not only by indigestible and highly inflammatory trans-fatty acids but an imbalance of pro-inflammatory omega-6 fatty acids. We use less anti-inflammatory omega-3 fatty acids and healthy olive oil than we do hydrogenated vegetable oils for cooking and salad dressings. Our intake of healthy fats from fatty fish, nuts, avocados, green leafy vegetables, and dark chocolate is exceeded by our intake of red meats, dairy products, and other animal product sources of pro-inflammatory arachidonic acid. Other common sources of unhealthy, pro-inflammatory fats are margarine, corn oil, cottonseed oil, peanut oil, sesame oil, soybean oil, sunflower oil, and any products with a long shelf life such as crackers, pastries, and chips. These products have such a long shelf life because of the trans-fats and partially hydrogenated fats imbedded in them prevent rancidity.
Our ancestors ate meats that were grass fed as well as wild game which had less fat content than feed-lot or commercially raised beef and poultry. These grass-fed and wild game animals have meat that is high in omega-3 fatty acids because it is concentrated from the natural plant sources.
The major sources of healthy fats are cold-water fish such as salmon, mackerel, sardines, tuna, and herring as well as flaxseed, nuts (particularly walnuts), avocados, and green leafy vegetables. Shellfish like clams and oysters, catfish, and our locally caught red snapper and flounder have smaller amounts of these omega-3 fatty acids. These are warm water creatures and do not require the fat stores of the cold-water varieties.
Research has shown that increased intake of such healthy fats can actually slow or even reverse atherosclerosis. In a 2003 Lancet article, Thies, et al. showed that patients scheduled for elective carotid endarterectomy who were placed on fish oil supplements had significantly improved plaque morphology at surgical pathology analysis(smoother more fibrous plaque caps, absence of inflammatory cells within the plaques, and high levels of essential fatty acids within the plaques) compared to controls on omega-6 fatty acids such as sunflower oil. This study was, in my view, one of the hallmark trials showing that omega-3 fatty acids can actually improve the condition of pre-existing atherosclerosis.
Of course, multiple other studies through the years have shown that even eating fish as little as once a week reduces the risk of sudden death in men and eating fish twice a week reduces CHD risk in women. Stroke risk is likewise lowered. The mechanism of action is likely related to the anti-inflammatory effects of fish oil plus its impact on decreasing platelet aggregation. The American Heart Association has recommended eating fish twice a week (salmon, sardines, tuna, mackerel, trout) along with flaxseed, canola, and soybean oil. They also recommend supplementation for at least 1 g/d of EPA +DHA (the essential fatty acids in fish oil) for secondary prevention. The GISSI trial from Italy found that in over 11,000 patients on only 1 gram of fish oil daily in the 3 months post MI, there was a 20% reduction in total mortality, a 10% reduction in recurrent MI, and 40% reduction in sudden death. Fish oil also lowers triglycerides as well and many physicians now can prescribe fish oil as Omacor®.
Based on data such as these, I routinely prescribe 2 grams of fish oil to all of my patients with cardiovascular disease or at risk or cardiovascular conditions, e.g., those with hypertension, dyslipidemias, diabetes, peripheral vascular disease, TIA history, etc. I recommend a high quality of fish oil such as Nordic Natural® or Spectrum® because of risks of mercury, PCB, dioxins, and other contaminants in lower quality fish oils. Pregnant women and children need to take special caution with certain kinds of fish and limit frequency of intake to once a week because of these concerns. In general, smaller fish, lower on the food chain such as white albacore tuna and sardines, are safer than larger fish such as blue tuna and mackerel. Farm raised salmon is lower in omega-3 fatty acids as these fish are generally fed a fish meal (like pink dog food) instead of their usual diet of plankton and smaller fish which help them accumulate the omega-3 fatty acids.
Beyond fish is the data on the Mediterranean diet. This diet is enjoyable and more tolerable than many low fat diets. It has been found to improved weight loss compared to other low fat diets but provides a risk reduction of 33% compared to the usual American Heart Association diet. The Mediterranean diet is rich in healthy fats such as fish and olive oil (an omega-9, mono-unsaturated fat) as well as abundant anti-oxidants from vegetables and fruit. The Mediterranean diet is perhaps the world’s healthiest diet. I subscribe to the cooking magazine, Cucina Italiana to keep up my flow of excellent Mediterranean recipes and cooking supplies. This diet is palatable, sustainable, and enjoyable. What more can you ask for meal planning?
Speaking of anti-oxidants, is there still a role for these in cardiovascular disease treatment or prevention? In recent years, several studies have found lack of benefit for Vitamin E in patients with CVD. There were a number of problems with these studies including the form of Vitamin E used and the degree to which the condition was already established. While intake of Vitamin E can reduce the first cardiovascular event, those with advanced disease are unlikely to have significant benefit, according to published literature. Food sources of Vitamin E are nuts, vegetable oils, wheat germ, avocados, asparagus, mangoes, and sweet potatoes. These foods have a mix of the kinds of vitamin E (mixed tocopherols and tocotrienols) that were not used in the clinical trials of Vitamin E which primarily used the alpha-tocopherol form only. I recommend that my patients at risk for CVD take 400 IU of mixed tocopherols/tocotrienols, the “natural” Vitamin E available at a slightly higher price in most quality health food stores. This preparation offers a more rational mix of Vitamin E constituents than that used in clinical trials. Because of a reciprocal relationship in metabolism, Vitamin E should be taken with Vitamin C (250-500 mg a day) to maximize and synergize cardiovascular benefits such as reducing oxidation of LDL.
Of course, eating foods containing Vitamin E and Vitamin C with their complex mix of micronutrients and other anti-oxidants is a very strong strategy.
Many other supplements are useful in cardiovascular disease. I prescribe Co-Enzyme Q 10 (Bluebonnet or Natural Factors brands gelcaps) at 50-100 mg/d for all patients on statin drugs since these drugs deplete the body stores of this essential energy co-factor. CoQ10 is also highly useful in some cases of congestive heart failure, particularly New York classes 1-3 though I have seen improved ejection fractions in patients with stage 4 disease with EF’s as low as 10-15% improving to 25-35%1. The B vitamins, B6(50-100mg/d), B12(200-800mcg/d) and folic acid (400mcg-2g/d) are useful in reducing homocysteine levels, an important coronary risk factor, though studies conflict on whether this affects CVD outcomes. Niacin, Vitamin B3 can be useful in reducing total cholesterol and in increasing HDL. Slow release compounds are best tolerated in doses of 1-3 grams a day. I advise that patients take an aspirin 30 minutes of so before dosing of Vitamin B3 which further reduces the risk of the skin flushing reaction. This reaction as commonly experienced is otherwise a deterrent to continuing niacin. Monitor liver enzymes on patients on niacin.
Resveratrol and other bioflavonoids found in red wine, nuts such as walnuts, and a diet with of five servings of fruits and vegetables daily is useful for cardiac prevention. The “French paradox” of reduced CVD risk despite a rich diet is probably not only due to red wine intake but also to the French diet which includes lots of salads as well as goodly portions of other fruits and vegetables.
Certain mind-body therapies are clearly useful in reducing adrenergic overload, e.g., Type A personality traits, that may contribute to CVD. Relaxation and stress management, guided imagery, social support, meditation, tai chi, yoga, and cognitive behavioral therapies all have been found useful in reducing cardiovascular risk. According to recent studies, tai chi and yoga have the benefits of moderate aerobic exercise. The treatment of depression is clearly an important component of reducing CVD risk.
Is chelation therapy useful in CVD? Chelation therapy is widely offered as an alternative for CVD though randomized trials for this therapy. Currently, a large NIH-funded study (TACT) is trying to determine if chelation is an effective therapy. Chelation therapists claim that it reduces cardiovascular symptoms and improves circulation by reducing heavy metal pro-oxidants, reducing inflammation, and perhaps by decreasing calcium in plaques. I do not commonly refer patients for chelation. For those patients who have chosen on their own to have chelation, I advise that as it is currently administered, it is safe but not yet proven. I am eager to see the result of the $35 million NIH TACT trial to see if benefits various patients have reported to me over the years stand up to scientific scrutiny.
I would like to close with a recommendation that anyone that cares for the hearts of patients read interventional/integrative cardiologist Dr. Mimi Guarneri’s wonderful book, The Heart Speaks2. She has created this collection of stories from her personal journals.
Part autobiography, part journey through the science of integrative cardiology, this is a must read for all those who have hearts. Not only does she describe very well the high tech side of modern interventional cardiology, she places it in a context that transcends the purely mechanistic with highly compelling, living metaphorical stories. Indeed, with the insight of a seasoned clinician, she weaves into her story vital themes that cannot be measured by EKG, echocardiography, stress tests, angiography, CT, or nuclear scans.
These stories are the often unheard, unacknowledged contributors to heart disease. Grief over the death of a child or spouse, a life-long pattern of hostility and anger, depression, stress, and the support of religious and spiritual experience: all these play an important role in how the heart lives…or dies. Each has the potential to injure as does hypertension, diabetes, or dyslipidemia. Yet addressing these subtle aspects of care may have as much power to protect and heal the heart as do many medical treatments.
Dr. Guarneri masterfully shares stories from her practice where technology alone was insufficient to heal a broken heart. Forgiveness, optimism, and gratitude are salves to a damaged heart. Relaxation, therapeutic touch, and prayer create synergies with fish oil and other heart healthy supplements, exercise, and diet that truly define integrative cardiology.
She closes with an emphasis on the art of healing through listening, caring, and connection. These are clearly intrinsic to her approach to integrative cardiology practice. It is an immensely powerful book. You will enjoy reading it and your practice and patients will benefit as well.
May your heart and the hearts of your patients be blessed, open, and healed.
1. Islam J, Uretsky B, Sierpina V. Heart failure improvement with CoQ10, hawthorn, and magnesium in a patient scheduled for cardiac resynchronization-defibrillator therapy: a case study. Explore. 2006;2(4):339-41.
2. Guarneri M. The Heart Speaks: A cardiologist reveals the secret language of healing. New York:Touchstone, 2006.
Posted
11/22/2006
Integrative Approaches in Sports Medicine and Orthopedics
Integrative Approaches in Sports Medicine and Orthopedics
Victor S. Sierpina, MD
3/22/06
Among the most prominent metaphors in our society is sports. Athletic activities, the athletes who star in them, and the excitement generated in competition are highly central to the American psyche. To win is to be acknowledged, honored, granted bonuses, and, of course, to receive the all important endorsement contract.
In the midst of this psyche, I would like to address some integrative medicine issues related to sports, first on a mind-body level, and then on the physical level. These issues have to do with enhancing performance, recovering quickly from injuries, and becoming the “best you can be.”
Without doubt, the “inner game” is now considered by trainers, sports psychologists, extreme athletes, and their coaches to be an essential part of training for ultimate performance. Besides physical conditioning and technical skills, attitude and disposition are now seen as what distinguishes the normal or average from the elite performers.
I have just enjoyed reading and listening to a CD series by Rice University performance psychologist, Dr. John Eliot. His book Overachievement, as well as his CD series Maverick Mind provide a fascinating insight into the difference between high performers and those whose performance is nothing less than exceptional. An expert in sports psychology, Dr. Eliot does not limit the scope of his research and comments to athletics. Much of his work has also been devoted to understanding peak performance issues in medicine and business. He gets into the minds of overachievers and debunks common myths such as “hard work is the answer,” or “don’t put all your eggs in one basket,” “be realistic,” and encourages moving from the “training mindset to the trusting mindset.”
In essence, as William James once said, “We are what we think about most of the time.” If we plan for performance and success, rehearse it mentally and emotionally, then we enjoy the process and can expect to achieve at our highest level. Focusing on the feeling of achievement enhances the ability we have to maximize the physical and technical skills we have in a sport, in business, or in medicine. For more details, get a copy of Dr. Eliot’s book and CD series.
Of course, athletes are always looking for the “edge” on a physical level. They try to enhance their competitive skills in endurance and strength, develop their bodies through weight loss and weight training, reduce pain and improve muscle recovery from injury, and increase energy production.
To deal with injuries, athletes use a variety of integrative methods. Acupuncture and massage are widely used by elite and professional athletes (even race horses!) to deal with injuries and return players back to the game. Chiropractic, osteopathic, and physical therapy approaches are also useful in rehabilitating from injuries. I regularly recommend Tai Chi, yoga, and hydrotherapy for therapeutic and rehabilitative approaches to painful injuries. Natural anti-inflammatories are particularly of interest in the wake of the concerns about COX-2 inhibitors and the side effects of NSAID’s. These include white willow (from which aspirin is derived), bromelain (from pineapple), tumeric, boswellia, ginger, devil’s claw, cat’s claw, topical calendula or comfrey. Use the dosage recommended on the bottle and you generally won’t go wrong.
While space does not permit detailed examination of all of these, the references below give a more in depth review. The bottom line is that there is little evidence that these products improve athletic performance and some of them, there is clear danger of harm. The most effective and well tested performance enhancer turnsout to be caffeine. Hail Starbucks!
Let’s briefly review these supplements. Creatine is very popular and an NCAA survey estimated that almost 60% of college athletes used it. It may be useful for improving performance of short duration, high intensity exercise such as sprinting or weight lifting. The dosing is 20g/d loading for 5days, then 2 g/d maintenance.Effects are based on building energy stores of Phosphocreatine (PCr)—an important source of energy in the initial seconds of maximal anaerobic exertion. Exercise must be maximal and anaerobic whic
